Development and Validation of a Clinical Predictive Nomogram for Assessing the Risk of Recurrence of Acute Pancreatitis in Combined Hypertriglyceridemia.

BACKGROUND: The objective of this study is to develop and validate a new nomogram-based scoring system for anticipating the recurrence of acute pancreatitis (AP) in combined hypertriglyceridemia (HTG). METHODS: A total of 292 patients diagnosed with AP combined with HTG participated in this research. Among them, 201 patients meeting the inclusion criteria were randomly divided into training and validation sets at a ratio of 7:3. Clinical data were collected for all patients. In the training set, predictive indicators were chosen through backward stepwise multivariable logistic regression analysis. Subsequently, a nomogram was developed based on the selected indicators. Finally, the model's performance was validated in both the training and validation sets. RESULTS: By employing backward stepwise multivariable logistic regression analysis, we identified diabetes, gallstones, alcohol consumption, and triglyceride levels as predictive indicators. Subsequently, a clinical nomogram that incorporates these four independent risk factors was constructed. Model validation demonstrated an AUC of 0.726 (95% CI 0.644-0.809) in the training set and an AUC of 0.712 (95% CI 0.583-0.842) in the validation set, indicating a good discriminative ability. The Hosmer-Lemeshow test yielded P-values of 0.882 and 0.536 in the training and validation sets, respectively, suggesting good calibration. Calibration curves further confirmed good agreement. Ultimately, decision curve analysis (DCA) emphasized the clinical utility of our model. CONCLUSION: We have developed a nomogram for predicting the recurrence of AP combined with HTG in patients, and this nomogram demonstrates good discriminative ability, calibration, and clinical utility. This tool holds the potential to assist clinicians in offering more personalized treatment strategies for AP combined with HTG.

Strategies to prevent blood loss and reduce transfusion in emergency general surgery, WSES-AAST consensus paper.

Emergency general surgeons often provide care to severely ill patients requiring surgical interventions and intensive support. One of the primary drivers of morbidity and mortality is perioperative bleeding. In general, when addressing life threatening haemorrhage, blood transfusion can become an essential part of overall resuscitation. However, under all circumstances, indications for blood transfusion must be accurately evaluated. When patients decline blood transfusions, regardless of the reason, surgeons should aim to provide optimal care and respect and accommodate each patient's values and target the best outcome possible given the patient's desires and his/her clinical condition. The aim of this position paper was to perform a review of the existing literature and to provide comprehensive recommendations on organizational, surgical, anaesthetic, and haemostatic strategies that can be used to provide optimal peri-operative blood management, reduce, or avoid blood transfusions and ultimately improve patient outcomes.

Association of admission serum triglyceride levels with intensive care unit hospitalization rates in acute pancreatitis patients: A retrospective study.

Acute pancreatitis (AP) is a complex and unpredictable condition, of which hypertriglyceridemia (HTG) is the third most prevalent cause. This study aimed to conduct a retrospective analysis of clinical data from hospitalized AP patients to uncover a potential correlation between triglyceride (TG) levels and the necessity for intensive care unit (ICU) admission. This retrospective cohort study utilized the Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV) critical care dataset, incorporating data from 698 patients with hypertriglyceridemic acute pancreatitis (HTG-AP). The analysis employed the RCS model along with univariate and multivariate logistic regression methods to affirm the association between triglyceride levels and ICU admission. Subgroup analysis was performed to investigate specific populations. The study included 698 patients with AP, 42.41% of whom experienced HTG during hospitalization. RCS analysis revealed a linear association between TG levels and risk of ICU admission (p for nonlinear = .219, p for overall = .009). Multivariate logistic regression analysis indicated an increased risk of ICU admission in the TG range of 1.7-5.65 mmol/L (aOR = 1.83, 95% CI 1.12-2.99, P = .015) and TG >11.3 mmol/L (aOR = 5.69, 95% CI 2.36-13.74, P < .001) compared to the normal group. Similar results were observed across the various subgroups. As triglyceride levels increased, there was a corresponding increase in ICU admissions. Patients within the 1.7 to 5.65 mmol/L and > 11.3 mmol/L triglyceride groups exhibited higher rates of ICU admissions. Moreover, we observed a higher risk of ICU hospitalization even with mild TG elevation.

The 2023 WSES guidelines on the management of trauma in elderly and frail patients.

BACKGROUND: The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. METHODS: Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. RESULTS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patient's directives, family feelings and representatives' desires, and all decisions should be shared. CONCLUSIONS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.

Acute Necrotizing Pancreatitis Complicated with Paroxysmal Nocturnal Haemoglobinuria: A Case Report.

This report presents a unique case of acute necrotizing pancreatitis(ANP) concomitant with paroxysmal nocturnal hemoglobinuria(PNH), a combination that has not been documented in existing literature. The impact of PNH on ANP and its treatment remains uncertain due to the lack of consensus. The case described herein involves a patient who exhibited both ANP and PNH, subsequently experiencing splanchnic vein thrombosis (SVT), resulting in substantial intra-abdominal and gastrointestinal hemorrhaging. We attempted to analyze the role of PNH in the formation of SVT in ANP and propose some new insights and hypotheses for the treatment of such patients.

Dose-Incorporated Deep Ensemble Learning for Improving Brain Metastasis Stereotactic Radiosurgery Outcome Prediction.

PURPOSE: To develop a novel deep ensemble learning model for accurate prediction of brain metastasis (BM) local control outcomes after stereotactic radiosurgery (SRS). METHODS AND MATERIALS: A total of 114 brain metastases (BMs) from 82 patients were evaluated, including 26 BMs that developed biopsy-confirmed local failure post-SRS. The SRS spatial dose distribution (Dmap) of each BM was registered to the planning contrast-enhanced T1 (T1-CE) magnetic resonance imaging (MRI). Axial slices of the Dmap, T1-CE, and planning target volume (PTV) segmentation (PTVseg) intersecting the BM center were extracted within a fixed field of view determined by the 60% isodose volume in Dmap. A spherical projection was implemented to transform planar image content onto a spherical surface using multiple projection centers, and the resultant T1-CE/Dmap/PTVseg projections were stacked as a 3-channel variable. Four Visual Geometry Group (VGG-19) deep encoders were used in an ensemble design, with each submodel using a different spherical projection formula as input for BM outcome prediction. In each submodel, clinical features after positional encoding were fused with VGG-19 deep features to generate logit results. The ensemble's outcome was synthesized from the 4 submodel results via logistic regression. In total, 10 model versions with random validation sample assignments were trained to study model robustness. Performance was compared with (1) a single VGG-19 encoder, (2) an ensemble with a T1-CE MRI as the sole image input after projections, and (3) an ensemble with the same image input design without clinical feature inclusion. RESULTS: The ensemble model achieved an excellent area under the receiver operating characteristic curve (AUCROC: 0.89 ± 0.02) with high sensitivity (0.82 ± 0.05), specificity (0.84 ± 0.11), and accuracy (0.84 ± 0.08) results. This outperformed the MRI-only VGG-19 encoder (sensitivity: 0.35 ± 0.01, AUCROC: 0.64 ± 0.08), the MRI-only deep ensemble (sensitivity: 0.60 ± 0.09, AUCROC: 0.68 ± 0.06), and the 3-channel ensemble without clinical feature fusion (sensitivity: 0.78 ± 0.08, AUCROC: 0.84 ± 0.03). CONCLUSIONS: Facilitated by the spherical image projection method, a deep ensemble model incorporating Dmap and clinical variables demonstrated excellent performance in predicting BM post-SRS local failure. Our novel approach could improve other radiation therapy outcome models and warrants further evaluation.

Biliary reconstruction with localized creation: One case report of repairing bile duct injury and defect with autografts.

INTRODUCTION: Bile duct injuries caused by any reason are a disaster for patients and pose a significant psychological and technical challenge for surgeons. The use of Ligamentum teres hepatis and gallbladder flap as autografts is showing promising results in the repair of bile duct injury. CASE PRESENTATION: This article presents a challenging case of a patient with Mirizzi syndrome who experienced a complex bile duct defect and injury during cholecystectomy. We describe the successful reconstruction of the bile duct using ligamentum teres hepatis and remnant gallbladder flap simultaneously. DISCUSSION: Ligamentum teres hepatis and remnant gallbladder flap are ideal repair materials for repairing and reconstructing bile duct injuries due to their easy availability, good tissue compatibility, and low incidence of postoperative complications. It is essential to seek the assistance of an experienced biliary surgeon when bile duct injury occurs during operation. CONCLUSION: Ligamentum teres hepatis and gallbladder flap, as suitable autologous tissues, are viable options for repairing bile duct injuries and defects.

Acute Necrotizing Pancreatitis Complicated With Sinistral Portal Hypertension And Mechanical Obstruction Of The Colon: A Case Report.

Acute necrotizing pancreatitis (ANP) is often associated with acute necrotic collection (ANC) or walled-off necrosis (WON). Due to the close anatomical connection between the pancreas, the spleen, and the transverse colon, necrotizing pancreatitis is often combined with spleen or colon involvement. Gastrointestinal dysfunction usually caused by pancreatitis leads to paralytic intestinal obstruction. However, pancreatitis combined with mechanical colonic obstruction is extremely rare. It can easily be misdiagnosed as malignant intestinal obstruction, and diagnosing the cause of intestinal obstruction becomes more critical when accompanied by Sinistral portal hypertension (SPH). Surgical resection is the primary method for the previous occurrence of colonic complications. In this case report, upon admission, a 37-year-old patient was diagnosed with acute necrotizing pancreatitis with sinistral portal hypertension. On the 6th day after admission, the patient developed a sudden colonic obstruction. After identifying the cause, the patient underwent a transanal decompression tube and minimally invasive necrosectomy, avoiding colon resection. In acute necrotizing pancreatitis combined with colonic mechanical obstruction, it is essential to clarify the etiology, and focus treatment on clearing the peripancreatic necrotic tissue, non-surgical treatment to deal with colonic obstruction is feasible, and the principle of individualized treatment should be used throughout the disease.

Independent Monte Carlo dose calculation identifies single isocenter multi-target radiosurgery targets most likely to fail pre-treatment measurement.

PURPOSE: For individual targets of single isocenter multi-target (SIMT) Stereotactic radiosurgery (SRS), we assess dose difference between the treatment planning system (TPS) and independent Monte Carlo (MC), and demonstrate persistence into the pre-treatment Quality Assurance (QA) measurement. METHODS: Treatment plans from 31 SIMT SRS patients were recalculated in a series of scenarios designed to investigate sources of discrepancy between TPS and independent MC. Targets with > 5% discrepancy in DMean[Gy] after progressing through all scenarios were measured with SRS MapCHECK. A matched pair analysis was performed comparing SRS MapCHECK results for these targets with matched targets having similar characteristics (volume & distance from isocenter) but no such MC dose discrepancy. RESULTS: Of 217 targets analyzed, individual target mean dose (DMean[Gy]) fell outside a 5% threshold for 28 and 24 targets before and after removing tissue heterogeneity effects, respectively, while only 5 exceeded the threshold after removing effect of patient geometry (via calculation on StereoPHAN geometry). Significant factors affecting agreement between the TPS and MC included target distance from isocenter (0.83% decrease in DMean[Gy] per 2 cm), volume (0.15% increase per cc), and degree of plan modulation (0.37% increase per 0.01 increase in modulation complexity score). SRS MapCHECK measurement had better agreement with MC than with TPS (2%/1 mm / 10% threshold gamma pass rate (GPR) = 99.4 ± 1.9% vs. 93.1 ± 13.9%, respectively). In the matched pair analysis, targets exceeding 5% for MC versus TPS also had larger discrepancies between TPS and measurement with no GPR (2%/1 mm / 10% threshold) exceeding 90% (71.5% ± 16.1%); whereas GPR was high for matched targets with no such MC versus TPS difference (96.5% ± 3.3%, p = 0.01). CONCLUSIONS: Independent MC complements pre-treatment QA measurement for SIMT SRS by identifying problematic individual targets prior to pre-treatment measurement, thus enabling plan modifications earlier in the planning process and guiding selection of targets for pre-treatment QA measurement.

Surgical Antibiotic Prophylaxis: A Proposal for a Global Evidence-Based Bundle.

In the multimodal strategy context, to implement healthcare-associated infection prevention, bundles are one of the most commonly used methods to adapt guidelines in the local context and transfer best practices into routine clinical care. One of the most important measures to prevent surgical site infections is surgical antibiotic prophylaxis (SAP). This narrative review aims to present a bundle for the correct SAP administration and evaluate the evidence supporting it. Surgical site infection (SSI) prevention guidelines published by the WHO, CDC, NICE, and SHEA/IDSA/APIC/AHA, and the clinical practice guidelines for SAP by ASHP/IDSA/SIS/SHEA, were reviewed. Subsequently, comprehensive searches were also conducted using the PubMed®/MEDLINE and Google Scholar databases, in order to identify further supporting evidence-based documentation. The bundle includes five different measures that may affect proper SAP administration. The measures included may be easily implemented in all hospitals worldwide and are based on minimal drug pharmacokinetics and pharmacodynamics knowledge, which all surgeons should know. Antibiotics for SAP should be prescribed for surgical procedures at high risk for SSIs, such as clean-contaminated and contaminated surgical procedures or for clean surgical procedures where SSIs, even if unlikely, may have devastating consequences, such as in procedures with prosthetic implants. SAP should generally be administered within 60 min before the surgical incision for most antibiotics (including cefazolin). SAP redosing is indicated for surgical procedures exceeding two antibiotic half-lives or for procedures significantly associated with blood loss. In principle, SAP should be discontinued after the surgical procedure. Hospital-based antimicrobial stewardship programmes can optimise the treatment of infections and reduce adverse events associated with antibiotics. In the context of a collaborative and interdisciplinary approach, it is essential to encourage an institutional safety culture in which surgeons are persuaded, rather than compelled, to respect antibiotic prescribing practices. In that context, the proposed bundle contains a set of evidence-based interventions for SAP administration. It is easy to apply, promotes collaboration, and includes measures that can be adequately followed and evaluated in all hospitals worldwide.

Effect of alfalfa supplementary change dietary non-fibrous carbohydrate (NFC) to neutral detergent fiber (NDF) ratio on rumen fermentation and microbial function in Gansu alpine fine wool sheep (Ovis aries).

Bodyweight loss and rumen microbial dysfunction of grazing sheep was a challenge for the sheep production industry during cold season, which were considered to correlated with under-roughage-feeding. Alfalfa is a good roughage supplementary for ruminants, which can improve grazing sheep bodyweight-loss and rumen microbial dysfunction during grass-withering period. This study evaluated the effects of alfalfa hay supplementary change dietary non-fibrous carbohydrate/neutral detergent fiber (NFC/NDF) ratios on rumen fermentation and microbial function of Gansu alpine fine wool sheep during extreme cold season. 120 ewes (3-4 yrs) with an average body weight of 28.71 ± 1.22 kg were allocated randomly into three treatments, and fed NFC/NDF of 1.92 (H group), 1.11 (M group), and 0.68 (L group), respectively. This study was conducted for 107 d, including 7 d of adaption to the diets. The rumen fermentation parameters and microbial characteristics were measured after the end of feeding trials. The results showed that the concentrations of sheep body weight, nitrogen components (Total-N, Soluble protein-N and Ammonia-N), blood biochemical indices (LDH, BUN and CHO) and ruminal volatile fatty acids (TVFA and propionate) significantly increased with an increase in the proportion of NFC/NDF ratios (p < .05), and the acetate and acetate/propionat ratio presented a contrary decreasing trend (p < .05). A total of 1018 OTUs were obtained with 97% consistency. Ruminococcus, Ruminococcaceae and Prevotella were observed as the predominant phyla in ruminal fluid microbiota. Higher NFC/NDF ratios with Alfalfa supplementary increased the richness and diversity of ruminal fluid microbiota, and decreased ruminal fluid microbiota beta-diversity. Using clusters of orthologous groups (COG), the ruminal fluid microbiota of alfalfa supplementary feeding showed low immune pathway and high carbohydrate metabolism pathway. In summary, the study suggested that there was an increasing tendency in dietary NFC/NDF ratio of 1.92 in body weight, ruminal fermentation, microbial community composition and fermentation characteristics through developing alfalfa supplementary system.

Cardiac-specific deletion of BRG1 ameliorates ventricular arrhythmia in mice with myocardial infarction.

Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+ current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and ß-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI.

Therapeutic effect of yinchenhao decoction on cholelithiasis via mucin in the gallbladder and intestine.

Cholelithiasis is a common and frequently occurring disease worldwide that belongs to the category of jaundice in traditional Chinese medicine. Yinchenhao decoction (YD) consists of Artemisia capillaris Thunb., Gardenia jasminoides J.Ellis, and Rheum palmatum L., and is traditionally used to treat jaundice, which has a significant therapeutic effect on cholelithiasis. Our study aimed to investigate the pathological mechanism of cholelithiasis and the therapeutic mechanism of YD via mucin in the gallbladder and intestine. YD was prepared and analyzed using HPLC. The supersaturation stability experiment was designed by the solvent-shift method. The cell transport experiment was conducted by coculture monolayers. The animal experiment was performed using a cholelithiasis model with a high-cholesterol diet. The related indicators were detected by automatic biochemical analyzer, PCR, western blot, or ELISA. Statistics were analyzed using χ2-tests and t-tests. As the results, in cholelithiasis, MUC5AC highly expressed in the gallbladder shortened cholesterol supersaturation and promoted cholesterol crystallization via the inflammatory cytokine signaling pathway; MUC2 highly expressed in the small intestine prolonged cholesterol supersaturation and promoted cholesterol absorption via the inflammatory cytokine signaling pathway. YD inhibited mucin expression in the gallbladder and intestine in a concentration-dependent manner for cholelithiasis treatment by inhibiting the inflammatory cytokine signaling pathway, which was attributed to the active components, including chlorogenic acid, geniposide, and rhein.

Photoredox/Enzymatic Catalysis Enabling Redox-Neutral Decarboxylative Asymmetric C-C Coupling for Asymmetric Synthesis of Chiral 1,2-Amino Alcohols.

Photocatalysis offers tremendous opportunities for enzymes to access new functions. Herein, we described a redox-neutral photocatalysis/enzymatic catalysis system for the asymmetric synthesis of chiral 1,2-amino alcohols via decarboxylative radical C-C coupling of N-arylglycines and aldehydes by combining an organic photocatalyst, eosin Y, and carbonyl reductase RasADH. Notably, this protocol avoids using any sacrificial reductants. A possible reaction mechanism proposed is that the transformation proceeds through sequential photoinduced decarboxylative radical addition to an aldehyde and a photoenzymatic deracemization pathway. This redox-neutral photoredox/enzymatic strategy is promising not only for effective synthesis of a series of chiral amino alcohols in a green and sustainable manner but also for the design of other novel C-C radical coupling transformations for the synthesis of bioactive molecules.

Enhanced perioperative care in emergency general surgery: the WSES position paper.

Enhanced perioperative care protocols become the standard of care in elective surgery with a significant improvement in patients' outcome. The key element of the enhanced perioperative care protocol is the multimodal and interdisciplinary approach targeted to the patient, focused on a holistic approach to reduce surgical stress and improve perioperative recovery. Enhanced perioperative care in emergency general surgery is still a debated topic with little evidence available. The present position paper illustrates the existing evidence about perioperative care in emergency surgery patients with a focus on each perioperative intervention in the preoperative, intraoperative and postoperative phase. For each item was proposed and approved a statement by the WSES collaborative group.

The role of BRG1 in epigenetic regulation of cardiovascular diseases.

Cardiovascular diseases have been closely linked to abnormal epigenetic regulation. In the context of epigenetic regulation, BRG1, a pivotal SWI/SNF chromatin remodeling enzyme, emerges as a key epigenetic regulator with significant impact on the development and progression of cardiovascular disorders. From the perspective of epigenetic regulation of cardiovascular diseases, BRG1 emerges as a pivotal SWI/SNF chromatin remodeling enzyme, functioning as a key epigenetic regulator. It exerts substantial influence on the development and progression of cardiovascular disorders by exerting precise control over gene expression and protein levels. Therefore, a comprehensive understanding of BRG1's epigenetic regulatory role in cardiovascular disease is essential for unraveling its underlying pathophysiological mechanisms. This paper summarizes and discusses the function of BRG1 in the epigenetic regulation of cardiovascular diseases.

Generation, validation, and benchmarking of a commercial independent Monte Carlo calculation beam model for multi-target SRS.

BACKGROUND: Dosimetric validation of single isocenter multi-target radiosurgery plans is difficult due to conditions of electronic disequilibrium and the simultaneous irradiation of multiple off-axis lesions dispersed throughout the volume. Here we report the benchmarking of a customizable Monte Carlo secondary dose calculation algorithm specific for multi-target radiosurgery which future users may use to guide their commissioning and clinical implementation. PURPOSE: To report the generation, validation, and clinical benchmarking of a volumetric Monte Carlo (MC) dose calculation beam model for single isocenter radiosurgery of intracranial multi-focal disease. METHODS: The beam model was prepared within SciMoCa (ScientificRT, Munich Germany), a commercial independent dose calculation software, with the aim of broad availability via the commercial software for use with single isocenter radiosurgery. The process included (1) definition & acquisition of measurement data required for beam modeling, (2) tuning model parameters to match measurements, (3) validation of the beam model via independent measurements and end-to-end testing, and finally, (4) clinical benchmarking and validation of beam model utility in a patient specific QA setting. We utilized a 6X Flattening-Filter-Free photon beam from a TrueBeam STX linear accelerator (Siemens Healthineers, Munich Germany). RESULTS: In addition to the measured data required for standard IMRT/VMAT (depth dose, central axis profiles & output factors, leaf gap), beam modeling and validation for single-isocenter SRS required central axis and off axis (5 cm & 9 cm) small field output factors and comparison between measurement and simulation of backscatter with aperture for jaw much greater than MLCs. Validation end-to-end measurements included SRS MapCHECK in StereoPHAN geometry (2%/1 mm Gamma = 99.2% ±â€¯2.2%), and OSL & scintillator measurements in anthropomorphic STEEV phantom (6 targets, volume = 0.1-4.1cc, distance from isocenter = 1.2-7.9 cm) for which mean difference was -1.9% ±â€¯2.2%. For 10 patient cases, MC for individual PTVs was -0.8% ±â€¯1.5%, -1.3% ±â€¯1.7%, and -0.5% ±â€¯1.8% for mean dose, D95%, and D1%, respectively. This corresponded to custom passing rates action limits per AAPM TG-218 guidelines of ±5.2%, ±6.4%, and ±6.3%, respectively. CONCLUSIONS: The beam modeling, validation, and clinical action criteria outlined here serves as a benchmark for future users of the customized beam model within SciMoCa for single isocenter radiosurgery of multi-focal disease.

Semirational Engineering of a Thermostable Carbonyl Reductase for the Precision Synthesis of (2R,3R)-2-Methyl-2-benzyl-3-hydroxycyclopentanone and Its Analogues.

2,2-Disubstituted-3-hydroxycyclopentanones are important chiral intermediates for natural products and pharmaceuticals. Through semirational engineering of a thermostable carbonyl reductase CBCR from Cupriavidus sp. BIS7, a mutant L91C/F93I was obtained. Mutant L91C/F93I showed 4- to 36-fold enhanced activities toward 2-methyl-2-benzyl-1,3-cyclopentanedione and its analogues, affording the (2R,3R)-stereoisomers with >99% ee and >99% de. Enzyme-substrate docking studies were performed to reveal the molecular basis for the activity and stereoselectivity improvements.

A structured FMEA approach to optimizing combinations of plan-specific quality assurance techniques for IMRT and VMAT QA.

BACKGROUND: Many commercial tools are available for plan-specific quality assurance (QA) of radiotherapy plans, with their functionality assessed in isolation. However, multiple QA tools are required to review the full range of potential errors. It is important to assess their effectiveness in combination with each other to look for ways to both streamline the QA process and to make certain that errors of high impact and/or high occurrence are caught before reaching patient treatment. PURPOSE: To develop a structured method to assess the effective risk reduction of combinations of QA methods for IMRT/VMAT treatments. METHODS: First, a structured prospective risk assessment was performed to establish the major failure modes (FMs) of IMRT/VMAT QA, and assign occurrence (O), severity (S), and baseline detectability (BD) rankings to them. The baseline assumed that chart checks and linear accelerator QA was performed, but no plan-specific secondary dose calculation or measurement was done. Second, the detectability of each FM for two secondary dose calculation methods and four plan measurement methods (point-based dose calculation, Monte-Carlo-based dose calculation, 2D fluence-based measurement, 2.5D phantom-based measurement, log file analysis with dose recalculation, and log file analysis combined with MLC QA) was determined. Third, we used a minimum detectability approach in addition to each FM's occurrence and severity to determine the optimal combination of QA methods. We analyzed the cumulative risk priority number of eight combinations of QA methods. The analysis was done on (1) all FMs, (2) FMs with high severity, (3) FMs with high-risk priority numbers (RPN) of O*S*BD, and (4) on FMs with both high severity and high RPN. RESULTS: Our analysis resulted in 54 FMs, including commissioning, planning, data transfer, and linear accelerator failures. 1D secondary dose calculation plus measurement provided a 19%-22% risk reduction from baseline. 1D/3D secondary dose calculation plus log files created a 25%-32% reduction. 3D secondary dose calculation plus measurement resulted in a 27%-34% reduction. 3D secondary dose calculation plus log files with additional machine QA provided the greatest reduction of 31%-42%. CONCLUSION: This novel structured approach to comparing combinations of QA methods will allow us to optimize our procedures, with the goal of detecting all clinically significant FMs. Our results show that log-file QA with 3D dose recalculation and supplemental machine QA provides better risk reduction than measurement-based QA. This work builds evidence to justify reducing or eliminating measurement-based PSQA with an independent 3D dose verification, log-file measurement, and appropriate supplementation of machine QA. The process also highlights FMs that cannot be caught by pre-treatment QA, prompting us to consider future directions for on-treatment QA.