Building Geriatric Trauma Programs in Resource-Constrained Environments: Trauma Quality Improvement Program Guideline Implementation at Two Safety Net Hospitals in Southern California.

Background: To improve care of geriatric trauma patients, the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) updated guidelines in 2021. Amid geriatrician shortages in Southern California, 2 Los Angeles County safety net hospitals were tasked with creating a strategy to meet geriatric trauma guidelines despite constrained resources. Methods: All trauma patients ≥ 60 years admitted to a safety net hospital in Southern California were enrolled without exclusions (August 2022-April 2023). Primary outcome was frailty screening with documentation to identify older trauma patients at a high risk for adverse outcomes. Results: Needs assessment discovered no standardized process to identify high-risk geriatric patients, no geriatric care guidelines, and no inpatient geriatric consultation service. An action plan composed of a resident-led frailty screen resulted in identification of high-risk patients. Overall, 217 patients met criteria. Ninety-six patients (44%) successfully underwent frailty screening. Frailty screening compliance increased over the study, beginning at 37% capture in the first month and increasing to 81% in the final study month. After achieving nearly uniform frailty screening, a form was developed for the EMR for ease of documentation, data capture/tracking, and compliance monitoring. Discussion: In this study, creativity, collaboration, and resourcefulness allowed TQIP guideline implementation at 2 county hospitals. A systematic process is now in place to identify and triage high-risk geriatric trauma patients based on frailty screen to receive inpatient medicine consultation for medical comorbidity optimization. Continued interdisciplinary and interfacility collaboration will be crucial for continued delivery of the optimal care to older injured patients.

Improving the performance of machine learning penicillin adverse drug reaction classification with synthetic data and transfer learning.

BACKGROUND: Machine learning may assist with the identification of potentially inappropriate penicillin allergy labels. Strategies to improve the performance of existing models for this task include the use of additional training data, synthetic data and transfer learning. AIMS: The aims of this study were to investigate the use of additional training data and novel machine learning strategies, namely synthetic data and transfer learning, to improve the performance of penicillin adverse drug reaction (ADR) machine learning classification. METHODS: Machine learning natural language processing was applied to free-text penicillin ADR data extracted from a public health system electronic health record (EHR). The models were developed by training on various labelled data sets. ADR entries were split into training and testing data sets and used to develop and test a variety of machine learning models. The effect of training on additional data and synthetic data versus the use of transfer learning was analysed. RESULTS: Following the application of these techniques, the area under the receiver operator curve of best-performing models for the classification of penicillin allergy (vs intolerance) and high-risk allergy (vs low-risk allergy) improved to 0.984 (using the artificial neural network model) and 0.995 (with the transfer learning approach) respectively. CONCLUSIONS: Machine learning models demonstrate high levels of accuracy in the classification and risk stratification of penicillin ADR labels using the reaction documented in the EHR. The model can be further optimised by incorporating additional training data and using transfer learning. Practical applications include automating case detection for penicillin allergy delabelling programmes.

Clinical factors and outcomes of spleen-conserving surgery versus total splenectomy in splenic injuries: A nationwide database study.

BACKGROUND: The objective of this study was to identify factors associated with the use of spleen-conserving surgeries, as well as patient outcomes, on a national scale. METHODS: This retrospective cohort study (2010-2015) included patients (age≥16 years) with splenic injury in the National Trauma Data Bank. Patients who received a total splenectomy or a spleen-conserving surgery were compared for demographics and clinical outcomes. RESULTS: During the study period, 18,425 received a total splenectomy and 1,825 received a spleen-conserving surgery. Total splenectomy was more likely to be performed for patients with age>65 (odds ratio [OR]: 0.63, p â€‹< â€‹0.001), systolic blood pressure<90 (OR: 0.63, p â€‹< â€‹0.001), heart rate>120 (OR: 0.83, p â€‹= â€‹0.007), and high-grade injuries (OR: 0.18, p â€‹< â€‹0.001). Penetrating trauma patients were more likely to undergo a spleen-conserving surgery (OR: 3.31, p â€‹< â€‹0.001). The use of spleen-conserving surgery was associated with a lower risk of pneumonia (OR: 0.79, p â€‹= â€‹0.009) and venous thromboembolism (OR: 0.72, p â€‹= â€‹0.006). CONCLUSIONS: Spleen-conserving surgeries may be considered for patients with penetrating trauma, age<65, hemodynamic stability, and low-grade injuries. Spleen-conserving surgeries have decreased risk of pneumonia and venous thromboembolism.

Vital sign measurements demonstrate terminal digit bias and boundary effects.

OBJECTIVE: The measurement and recording of vital signs may be impacted by biases, including preferences for even and round numbers. However, other biases, such as variation due to defined numerical boundaries (also known as boundary effects), may be present in vital signs data and have not yet been investigated in a medical setting. We aimed to assess vital signs data for such biases. These parameters are clinically significant as they influence care escalation. METHODS: Vital signs data (heart rate, respiratory rate, oxygen saturation and systolic blood pressure) were collected from a tertiary hospital electronic medical record over a 2-year period. These data were analysed using polynomial regression with additional terms to assess for underreporting of out-of-range observations and overreporting numbers with terminal digits of 0 (round numbers), 2 (even numbers) and 5. RESULTS: It was found that heart rate, oxygen saturation and systolic blood pressure demonstrated 'boundary effects', with values inside the 'normal' range disproportionately more likely to be recorded. Even number bias was observed in systolic heart rate, respiratory rate and blood pressure. Preference for multiples of 5 was observed for heart rate and blood pressure. Independent overrepresentation of multiples of 10 was demonstrated in heart rate data. CONCLUSION: Although often considered objective, vital signs data are affected by bias. These biases may impact the care patients receive. Additionally, it may have implications for creating and training machine learning models that utilise vital signs data.

Antibiotic prophylaxis in immunosuppressed patients - Missed opportunities from trimethoprim-sulfamethoxazole allergy label.

Trimethoprim-sulfamethoxazole (TMP-SMX) is a broad spectrum antibiotic in use for more than 50 years. It has an important indication as first line agent in the prophylaxis of opportunistic infections, particularly Pneumocystis jirovecii pneumonia (PJP), in immunosuppressed patients. For those who have a history of allergy or severe intolerance to TMP-SMX, pentamidine, dapsone or atovaquone may be substituted; however there is evidence that TMP-SMX offers superior coverage for PJP, toxoplasmosis, and nocardiosis. Compared to pentamidine, it has the added benefit of cost-effectiveness and self-administration as opposed to required hospital attendance for administration. Many patients who report a history of allergy or adverse reaction to TMP-SMX (or "sulfur allergy") will be found not to be allergic; and even those who are allergic may be able to be desensitized. The evaluation and, where appropriate, removal of TMP-SMX allergy label enables the use of TMP-SMX for prophylaxis against opportunistic infections. This is a cost-effective intervention to optimize antimicrobial prescribing and reduce the risk of opportunistic infections in immunosuppressed patients.

Tracing the barriers to decarbonising ophthalmology: A review.

As climate change demands increasingly urgent mitigation of greenhouse gas emissions, the health sector needs to do its part to decarbonise. Ophthalmologists share concerns about climate change and seek opportunities to reduce their environmental impact. When measuring the footprint of ophthalmology, major contributions are from patient travel to clinics, and from the large amounts of single-use disposable materials that are consumed during surgeries and sterile procedures. Ophthalmic services in India have already demonstrated systems that consume far fewer of these products through efficient throughput of patients and the safe reuse of many items, while maintaining equivalent safety and quality outcomes. Choosing these low-cost low-emission options would seem obvious, but many ophthalmologists experience barriers that prevent them operating as Indian surgeons do. Understanding these barriers to change is a crucial step in the decarbonisation of ophthalmology and the health sector more broadly.

Multifunctional 5-hydroxyconiferaldehyde O-methyltransferases (CAldOMTs) in plant metabolism.

Lignin, flavonoids, melatonin, and stilbenes are plant specialized metabolites with diverse physiological and biological functions, supporting plant growth and conferring stress resistance. Their biosynthesis requires O-methylations catalyzed by 5-hydroxyconiferaldehyde O-methyltransferase (CAldOMT; also called caffeic acid O-methyltransferase, COMT). CAldOMT was first known for its roles in syringyl (S) lignin biosynthesis in angiosperm cell walls and later found to be multifunctional. This enzyme also catalyzes O-methylations in flavonoid, melatonin, and stilbene biosynthetic pathways. Phylogenetic analysis indicated the convergent evolution of enzymes with OMT activities towards the monolignol biosynthetic pathway intermediates in some gymnosperm species that lack S-lignin and Selaginella moellendorffii, a lycophyte which produces S-lignin. Furthermore, neofunctionalization of CAldOMTs occurred repeatedly during evolution, generating unique O-methyltransferases (OMTs) with novel catalytic activities and/or accepting novel substrates, including lignans, 1,2,3-trihydroxybenzene, and phenylpropenes. This review summarizes multiple aspects of CAldOMTs and their related proteins in plant metabolism and discusses their evolution, molecular mechanism, and roles in biorefineries, agriculture, and synthetic biology.

Disruption of p-coumaroyl-CoA:monolignol transferases in rice drastically alters lignin composition.

Grasses are abundant feedstocks that can supply lignocellulosic biomass for production of cell-wall-derived chemicals. In grass cell walls, lignin is acylated with p-coumarate. These p-coumarate decorations arise from the incorporation of monolignol p-coumarate conjugates during lignification. A previous biochemical study identified a rice (Oryza sativa) BAHD acyltransferase (AT) with p-coumaroyl-CoA:monolignol transferase (PMT) activity in vitro. In this study, we determined that that enzyme, which we name OsPMT1 (also known as OsAT4), and the closely related OsPMT2 (OsAT3) harbor similar catalytic activity toward monolignols. We generated rice mutants deficient in either or both OsPMT1 and OsPMT2 by CRISPR/Cas9-mediated mutagenesis and subjected the mutants' cell walls to analysis using chemical and nuclear magnetic resonance methods. Our results demonstrated that OsPMT1 and OsPMT2 both function in lignin p-coumaroylation in the major vegetative tissues of rice. Notably, lignin-bound p-coumarate units were undetectable in the ospmt1 ospmt2-2 double-knockout mutant. Further, in-depth structural analysis of purified lignins from the ospmt1 ospmt2-2 mutant compared with control lignins from wild-type rice revealed stark changes in polymer structures, including alterations in syringyl/guaiacyl aromatic unit ratios and inter-monomeric linkage patterns, and increased molecular weights. Our results provide insights into lignin polymerization in grasses that will be useful for the optimization of bioengineering approaches for the effective use of biomass in biorefineries.

Witnessed prehospital traumatic arrest: predictors of survival to hospital discharge.

PURPOSE: Trauma patients are rapidly transported to the hospital for definitive care. Nonetheless, some are alive upon Emergency Medical Services (EMS) arrival but arrest on-scene or during transport. The study objective was to examine EMS-witnessed traumatic arrests to define patients who survived hospital discharge. METHODS: Patients sustaining EMS-witnessed traumatic arrest and entered into the National Trauma Data Bank were included (2007-2018). Mortality defined groups: survival to hospital discharge vs. in-hospital death vs. death in ED/declared dead on arrival (DOA). ANOVA/Chi-square compared cohorts. Multivariable analysis established factors associated with survival out of ED and to hospital discharge. RESULTS: After exclusions, 14,177 patients met the criteria: 10% survived, 22% died in hospital, and 68% died in ED/DOA. Survivors tended to be female (33% vs. 23% vs. 23%, p < 0.001), blunt traumas (71% vs. 56% vs. 60%, p < 0.001), have higher scene GCS (15 [7-15] vs. 3 [3-11] vs. 3 [3-7], p < 0.001), and lower injury severity (ISS 13 [7-26] vs. 27 [18-41] vs. 25 [10-30], p < 0.001), particularly of the head (AIS 0 [0-2] vs. 0 [0-4] vs. 1 [0-4], p < 0.001). Survival to hospital discharge was independently associated with higher field GCS (OR 1.252, p < 0.001) and SBP (OR 1.006, p < 0.001), and Head AIS scores (OR 1.073, p < 0.001). Increasing age (OR 0.984, p < 0.001), higher ISS (OR 0.975, p < 0.001), male sex (OR 0.695, p < 0.001), and penetrating mechanism of injury (OR 0.537, p < 0.001) were associated with reduced survival to discharge. CONCLUSION: After EMS-witnessed traumatic cardiac arrest, survivors were more likely to be young, female, injured by blunt trauma, and less hypotensive/comatose on-scene. These findings may have implications for ED resuscitation or declaration of care futility and should be further investigated with a prospective multicenter study.

Intravenous immunoglobulin alteration in response to adverse reactions in neurological conditions: A retrospective cohort study.

INTRODUCTION: Intravenous immunoglobulin (IVIg) is an important treatment in a range of neurological conditions. There is currently limited evidence regarding the frequency and management of IVIg-associated adverse reactions (AR) in neurological disorders. METHODS: A single-centre 18-month retrospective cohort study was conducted for all patients at a single tertiary hospital receiving IVIg as an inpatient or the medical day unit. Electronic medical record AR and alerts were reviewed for entries relating to IVIg, and prescribing records associated with recent IVIg administration were reviewed for the use of premedications. Case note review was undertaken to identify AR associated with alterations in IVIg treatment (such as reduction in rate, use of premedications or cessation of IVIg). Demographic, patient, and treatment factors were analysed for associations with AR necessitating alteration in IVIg treatment. RESULTS: This study included 98 individuals who received IVIg during the study period. Of these, 12 (12.1%) patients required an alteration in their IVIg treatment. In total, 3 (3.1%) of the 98 included patients required a reduced rate of IVIg, and 10 (10.2%) patients received premedication. The most common premedications were normal saline at the time of the infusion, cetirizine, and hydrocortisone. No demographic factors, indications or comorbidities were found to be associated with an increased likelihood of AR. However, an IVIg daily dose of >35 g and >45 g were associated with an increased likelihood of requiring IVIg treatment alteration due to AR. CONCLUSIONS: Alterations to IVIg treatment due to AR are commonly required in neurology patients, and may be associated with higher daily doses of IVIg.

Artificial intelligence-enabled penicillin allergy delabelling: an implementation study.

Inaccurate penicillin allergy labels may be delabelled following evaluation. The intervention in this study was an email-based notification system regarding the appropriateness for penicillin allergy evaluation, with a view to delabelling, as identified by a deep learning artificial intelligence algorithm. Of the intervention group (n = 59), three (5.1%) individuals had their penicillin allergies delabelled, which was significantly more than the control group (0%, P = 0.002). Further research to optimise such approaches is required.

Surgery's Rosetta Stone: Natural language processing to predict discharge and readmission after general surgery.

BACKGROUND: This study aimed to examine the accuracy with which multiple natural language processing artificial intelligence models could predict discharge and readmissions after general surgery. METHODS: Natural language processing models were derived and validated to predict discharge within the next 48 hours and 7 days and readmission within 30 days (based on daily ward round notes and discharge summaries, respectively) for general surgery inpatients at 2 South Australian hospitals. Natural language processing models included logistic regression, artificial neural networks, and Bidirectional Encoder Representations from Transformers. RESULTS: For discharge prediction analyses, 14,690 admissions were included. For readmission prediction analyses, 12,457 patients were included. For prediction of discharge within 48 hours, derivation and validation data set area under the receiver operator characteristic curves were, respectively: 0.86 and 0.86 for Bidirectional Encoder Representations from Transformers, 0.82 and 0.81 for logistic regression, and 0.82 and 0.81 for artificial neural networks. For prediction of discharge within 7 days, derivation and validation data set area under the receiver operator characteristic curves were, respectively: 0.82 and 0.81 for Bidirectional Encoder Representations from Transformers, 0.75 and 0.72 for logistic regression, and 0.68 and 0.67 for artificial neural networks. For readmission prediction within 30 days, derivation and validation data set area under the receiver operator characteristic curves were, respectively: 0.55 and 0.59 for Bidirectional Encoder Representations from Transformers and 0.77 and 0.62 for logistic regression. CONCLUSION: Modern natural language processing models, particularly Bidirectional Encoder Representations from Transformers, can effectively and accurately identify general surgery patients who will be discharged in the next 48 hours. However, these approaches are less capable of identifying general surgery patients who will be discharged within the next 7 days or who will experience readmission within 30 days of discharge.

Opioid prescribing, pain, and hospital stay of general surgery patients with oxycodone allergies in South Australia.

BACKGROUND: The frequency of oxycodone adverse reactions, subsequent opioid prescription, effect on pain and patient care in general surgery patients are not well known. This study aimed to determine prevalence of documented oxycodone allergy and intolerances (independent variables) in a general surgical cohort, and association with prescribing other analgesics (particularly opioids), subjective pain scores, and length of hospital stay (dependent variables). METHODS: This retrospective cohort study included general surgery patients from two South Australian hospitals between April 2020 and March 2022. Multivariable logistic regression evaluated associations between previous oxycodone allergies and intolerances, prescription records, subjective pain scores, and length of hospital stay. RESULTS: Of 12 846 patients, 216 (1.7%) had oxycodone allergies, and 84 (0.7%) oxycodone intolerances. The 216 oxycodone allergy patients had lower odds of receiving oxycodone (OR 0.17, P < 0.001), higher odds of tramadol (OR 3.01, P < 0.001) and tapentadol (OR 2.87, P = 0.001), but 91 (42.3%) still received oxycodone and 19 (8.8%) morphine. The 84 with oxycodone intolerance patients had lower odds of receiving oxycodone (OR 0.23, P < 0.001), higher odds of fentanyl (OR 3.6, P < 0.001) and tramadol (OR 3.35, P < 0.001), but 42 (50%) still received oxycodone. Patients with oxycodone allergies and intolerances had higher odds of elevated subjective pain (OR 1.60, P = 0.013; OR 2.36, P = 0.002, respectively) and longer length of stay (OR 1.36, P = 0.038; OR 2.24, P = 0.002, respectively) than patients without these. CONCLUSIONS: General surgery patients with oxycodone allergies and intolerances are at greater risk of worse postoperative pain and longer length of stay, compared to patients without. Many still receive oxycodone, and other opioids that could cause cross-reactivity.

Examining the independent risk factors for withdrawal of life sustaining treatment in trauma patients.

INTRODUCTION: Withdrawal of life sustaining treatment (WLST) occurs when medical intervention no longer benefits a patient's acute goals for care. The incidence of WLST in the trauma patient population is not well understood. The purpose of this study was to examine the incidence and independent risk factors associated with WLST. METHODS: The Trauma Quality Improvement Program (2017-2018) was utilized. Patients arrived without signs of life or without mortality or WLST data were excluded. Demographics, injury data, and outcomes were analyzed. Categorical variables are presented as number (percentage) and continuous variables as median [interquartile range]. WLST and non-WLST patients were compared. Early (<24 h) WLST patients were compared to all other WLST patients. RESULTS: Of 749,754 patients, 35,464 (4.7 %) died. Of these, 19,424 (2.6 %) died after WLST, constituting 54.8 % of all deaths. Median age was 67 [50-79], 67.6 % male, 17,557 (90.4 %) blunt injuries, 11,334 (58.4 %) GCS < 9. Median ISS 26 [17-30]. Median head AIS 4 (3-5). The WLST group had a much higher incidence of elderly (60+) patients (65.1% vs 41.0 %), blunt mechanism of injury (90.4% vs 76.9 %) and hypertension (43.5% vs 26.5 %). Black patients (8.2% vs 19.5 %) and Hispanic patients (7.9% vs 12.2 %) were less likely to undergo WLST. On multivariate analysis, patients 80+ years old (OR 12.939, p < 0.001), GCS < 9 (OR 15.621, p < 0.001), and head AIS = 5, head AIS = 6 (OR 3.886, p < 0.001 and OR 5.283, p < 0.001) were independently associated with WLST. GCS < 9 (OR 4.006, p < 0.001) and penetrating injury (OR 2.825, p < 0.001) were independently associated with early WLST within 24 h. CONCLUSIONS: More than half who die from trauma undergo withdrawal of life sustaining treatment. Elderly patients and those with severe TBI and low GCS scores are at high risk of experiencing withdrawal of life sustaining treatment. Further prospective evaluation is warranted.

Prevalence of Trimethoprim-Sulfamethoxazole Adverse Reaction Mislabelling in Australia.

INTRODUCTION: Trimethoprim-sulfamethoxazole (TMP-SMX) is an important antibiotic, with the most compelling indications for Pneumocystis jirovecii pneumonia prophylaxis and methicillin-resistant Staphylococcus aureus treatment. Previous adverse reactions (AR) to TMP-SMX may limit the usability of TMP-SMX. Electronic medical record (EMR) of AR for other antibiotics has previously been shown to be inaccurate; however, the extent to which this occurs for TMP-SMX is unknown. METHODS: A multi-centre retrospective observational study was conducted for consecutive inpatient admissions over a 2.5-year period commencing 2020. Adverse reactions to TMP-SMX recorded in the EMR were collected and reviewed by two independent medical officers using pre-defined expert criteria for the classification of allergies and intolerances. RESULTS: TMP-SMX AR were present in the EMR of 759 individuals (prevalence 0.6%). The majority were labelled as allergy (725, 95.5%) rather than intolerance (34, 4.5%). Most common AR were rash, vomiting, and swelling. When classified against the gold-standard expert criteria, there were 437 allergies (57.6%) and 159 intolerances (21.0%). Overall, the number of incorrect EMR AR labels was 133/759 (17.5%). Both medical and surgical specialties had significant numbers of patients with TMP-SMX AR labels and incorrectly classified EMR AR labels. CONCLUSION: TMP-SMX AR labels affect inpatients admitted under multiple specialty units. The user-entered categorization as allergy or intolerance labels in EMRs are frequently used incorrectly. These incorrect labels may inappropriately contraindicate the use of TMP-SMX, and formal evaluation of TMP-SMX ARs with immunological assessment and relabelling where appropriate may increase the use of this agent.

Vital signs and medical emergency response (MER) activation predict in-hospital mortality in general surgery patients: a study of 15 969 admissions.

BACKGROUND: The applicability of the vital signs prompting medical emergency response (MER) activation has not previously been examined specifically in a large general surgical cohort. This study aimed to characterize the distribution, and predictive performance, of four vital signs selected based on Australian guidelines (oxygen saturation, respiratory rate, systolic blood pressure and heart rate); with those of the MER activation criteria. METHODS: A retrospective cohort study was conducted including patients admitted under general surgical services of two hospitals in South Australia over 2 years. Likelihood ratios for patients meeting MER activation criteria, or a vital sign in the most extreme 1% for general surgery inpatients (<0.5th percentile or > 99.5th percentile), were calculated to predict in-hospital mortality. RESULTS: 15 969 inpatient admissions were included comprising 2 254 617 total vital sign observations. The 0.5th and 99.5th centile for heart rate was 48 and 133, systolic blood pressure 85 and 184, respiratory rate 10 and 31, and oxygen saturations 89% and 100%, respectively. MER activation criteria with the highest positive likelihood ratio for in-hospital mortality were heart rate ≤ 39 (37.65, 95% CI 27.71-49.51), respiratory rate ≥ 31 (15.79, 95% CI 12.82-19.07), and respiratory rate ≤ 7 (10.53, 95% CI 6.79-14.84). These MER activation criteria likelihood ratios were similar to those derived when applying a threshold of the most extreme 1% of vital signs. CONCLUSIONS: This study demonstrated that vital signs within Australian guidelines, and escalation to MER activation, appropriately predict in-hospital mortality in a large cohort of patients admitted to general surgical services in South Australia.

Focus on reuse: reducing waste associated with topical preoperative antiseptics.

PURPOSE: To outline the environmental and financial costs associated with single-use topical antiseptic (5% povidone-iodine [PVI] solution) in the ophthalmology theatre setting and explore potential methods of repurposing topical antiseptics. SETTING: Large tertiary referral center (Flinders Medical Centre, Adelaide, Australia). DESIGN: Single-center prospective observational study. METHODS: Dedicated containers placed in the ophthalmology theatre of the participating institution were used to collect the number of disposed PVI bottles over the 3-week study period. Descriptive statistics were employed to determine the associated packaging bottle weight, mean unused quantity (mL) and cost of the single-use topical PVI solution and costs of unused antiseptic. RESULTS: The total amount of waste generated from the use of single-use PVI bottles during the surveillance period was 10.823 kg, of which 21.9% was preventable; 72% of unused PVI by weight were discarded during the study period, equating to approximately $21 857.60 in wasted pharmaceutical content per year. 100% of the discarded PVI was successfully redirected and reused at a local wildlife rescue organisation and diverted from landfill. CONCLUSIONS: This study has demonstrated that the utilization of single-use topical preoperative PVI preparations is associated with significant financial, pharmaceutical and environmental waste. Future studies examining the recyclability of single-use PVI bottles and investigating systematic strategies to recycle and repurpose this waste are required.

A systematic review of the symptomatic management of Lhermitte's phenomenon.

INTRODUCTION: Lhermitte's phenomenon (LP) is a transient shock-like sensation that radiates down the spine into the extremities, usually with neck flexion. The potential efficacy and tolerability of various symptomatic therapies in the management of LP have not been systematically reviewed previously. METHOD: A systematic review was conducted using PubMed, EMBASE, and the Cochrane Library from inception to August 2022 for peer-reviewed articles describing the treatment of patients with Lhermitte's phenomenon. The review adheres to the PRISMA guidelines and was registered on PROSPERO. RESULTS: This systematic review included sixty-six articles, which included 450 patients with LP. Treatment of the underlying cause varied by aetiology. Whilst LP is most commonly considered in the context of structural pathology of the cervical cord, medication-induced LP was a common theme in the literature. The most common cause of medication-induced LP was platinum-based chemotherapy agents such as cisplatin and oxaliplatin. In medication-induced LP, symptoms typically resolved with cessation of the causative agent. Non-pharmacological treatment options were associated with mild-moderate symptomatic improvement. The most commonly used agents to treat patients with LP were carbamazepine and gabapentin, which resulted in variable degrees of symptomatic benefit. CONCLUSIONS: No randomised studies currently exist to support the use of symptomatic therapies to treat LP. Observational data suggest that some therapies may yield a symptomatic benefit in the management of LP. However, this systematic review identified a significant paucity of evidence in the literature, which suggests that further controlled studies are needed to investigate the optimal management of this common neurologic phenomenon.

Regioselective stilbene O-methylations in Saccharinae grasses.

O-Methylated stilbenes are prominent nutraceuticals but rarely produced by crops. Here, the inherent ability of two Saccharinae grasses to produce regioselectively O-methylated stilbenes is reported. A stilbene O-methyltransferase, SbSOMT, is first shown to be indispensable for pathogen-inducible pterostilbene (3,5-bis-O-methylated) biosynthesis in sorghum (Sorghum bicolor). Phylogenetic analysis indicates the recruitment of genus-specific SOMTs from canonical caffeic acid O-methyltransferases (COMTs) after the divergence of Sorghum spp. from Saccharum spp. In recombinant enzyme assays, SbSOMT and COMTs regioselectively catalyze O-methylation of stilbene A-ring and B-ring respectively. Subsequently, SOMT-stilbene crystal structures are presented. Whilst SbSOMT shows global structural resemblance to SbCOMT, molecular characterizations illustrate two hydrophobic residues (Ile144/Phe337) crucial for substrate binding orientation leading to 3,5-bis-O-methylations in the A-ring. In contrast, the equivalent residues (Asn128/Asn323) in SbCOMT facilitate an opposite orientation that favors 3'-O-methylation in the B-ring. Consistently, a highly-conserved COMT is likely involved in isorhapontigenin (3'-O-methylated) formation in wounded wild sugarcane (Saccharum spontaneum). Altogether, our work reveals the potential of Saccharinae grasses as a source of O-methylated stilbenes, and rationalize the regioselectivity of SOMT activities for bioengineering of O-methylated stilbenes.