Beyond the cuff: a consideration of factors that affect sexual function after benign hysterectomy.

PURPOSE OF REVIEW: Hysterectomy is the most common gynecologic surgical procedure performed on women in the United States. While there are data supporting that hysterectomy for benign indication often does not reduce sexual function and may in fact improve sexual function as fibroids and endometriosis are resected, it remains unclear if there are factors within the perioperative period that affect sexual function in the years following surgery. To date, there is no consensus on what factors can optimize patients' sexual function after hysterectomy. RECENT FINDINGS: We present the current literature that assesses factors which may contribute to sexual function after hysterectomy. Preoperative demographic factors, including increasing age, pelvic pain, and preoperative sexual dysfunction, play a large role in postoperative sexual function. Perioperatively, there is a growing amount of data suggesting that premenopausal salpingo-oophorectomy at the time of hysterectomy may increase the risk of sexual dysfunction after hysterectomy, and no conclusive evidence that subtotal hysterectomy improves sexual function. The route of hysterectomy and technique of cuff closure can impact sexual function after hysterectomy due to the risk of shortening the vaginal length. SUMMARY: There is a lack of high-quality evidence that can provide a consensus on factors to optimize sexual function after hysterectomy. A growing area of research in the excision of endometriosis procedures is the consideration of nerve-sparing surgery. Considering the many variables that exist when counseling a patient on benign hysterectomy and its effects on sexual function, it is critical to understand the current research that exists with regards to these factors.

Optimizing accrual to a large-scale, clinically integrated randomized trial in anesthesiology: A 2-year analysis of recruitment.

BACKGROUND: Performing large randomized trials in anesthesiology is often challenging and costly. The clinically integrated randomized trial is characterized by simplified logistics embedded into routine clinical practice, enabling ease and efficiency of recruitment, offering an opportunity for clinicians to conduct large, high-quality randomized trials under low cost. Our aims were to (1) demonstrate the feasibility of the clinically integrated trial design in a high-volume anesthesiology practice and (2) assess whether trial quality improvement interventions led to more balanced accrual among study arms and improved trial compliance over time. METHODS: This is an interim analysis of recruitment to a cluster-randomized trial investigating three nerve block approaches for mastectomy with immediate implant-based reconstruction: paravertebral block (arm 1), paravertebral plus interpectoral plane blocks (arm 2), and serratus anterior plane plus interpectoral plane blocks (arm 3). We monitored accrual and consent rates, clinician compliance with the randomized treatment, and availability of outcome data. Assessment after the initial year of implementation showed a slight imbalance in study arms suggesting areas for improvement in trial compliance. Specific improvement interventions included increasing the frequency of communication with the consenting staff and providing direct feedback to clinician investigators about their individual recruitment patterns. We assessed overall accrual rates and tested for differences in accrual, consent, and compliance rates pre- and post-improvement interventions. RESULTS: Overall recruitment was extremely high, accruing close to 90% of the eligible population. In the pre-intervention period, there was evidence of bias in the proportion of patients being accrued and receiving the monthly block, with higher rates in arm 3 (90%) compared to arms 1 (81%) and 2 (79%, p = 0.021). In contrast, in the post-intervention period, there was no statistically significant difference between groups (p = 0.8). Eligible for randomization rate increased from 89% in the pre-intervention period to 95% in the post-intervention period (difference 5.7%; 95% confidence interval = 2.2%-9.4%, p = 0.002). Consent rate increased from 95% to 98% (difference of 3.7%; 95% confidence interval = 1.1%-6.3%; p = 0.004). Compliance with the randomized nerve block approach was maintained at close to 100% and availability of primary outcome data was 100%. CONCLUSION: The clinically integrated randomized trial design enables rapid trial accrual with a high participant compliance rate in a high-volume anesthesiology practice. Continuous monitoring of accrual, consent, and compliance rates is necessary to maintain and improve trial conduct and reduce potential biases. This trial methodology serves as a template for the implementation of other large, low-cost randomized trials in anesthesiology.

Paravertebral and erector spinae plane blocks decrease length of stay compared with local infiltration analgesia in autologous breast reconstruction.

BACKGROUND: Autologous breast reconstruction is associated with significant pain impeding early recovery. Our objective was to evaluate the impact of replacing surgeon-administered local infiltration with preoperative paravertebral (PVB) and erector spinae plane (ESP) blocks for latissimus dorsi myocutaneous flap reconstruction. METHODS: Patients who underwent mastectomy with latissimus flap reconstruction from 2018 to 2022 were included in three groups: local infiltration, PVB, and ESP blocks. Block effect on postoperative length of stay (LOS) and the association between block status and pain, opioid consumption, time to first analgesic, and postoperative antiemetic administration were assessed. RESULTS: 122 patients met the inclusion criteria for this retrospective cohort study: no block (n=72), PVB (n=26), and ESP (n=24). On adjusted analysis, those who received a PVB block had a 20-hour shorter postoperative stay (95% CI 11 to 30; p<0.001); those who received ESP had a 24-hour (95% CI 15 to 34; p<0.001) shorter postoperative stay compared with the no block group, respectively. Using either block was associated with a reduction in intraoperative opioids (23 morphine milligram equivalents (MME)), 95% CI 14 to 31, p<0.001; ESP versus no block: 23 MME, 95% CI 14 to 32, p<0.001). CONCLUSIONS: Replacing surgical infiltration with PVB and ESP blocks for autologous breast reconstruction reduces LOS. The comparable reduction in LOS suggests that ESP may be a viable alternative to PVB in patients undergoing latissimus flap breast reconstruction following mastectomy. Further research should investigate whether ESP or PVB have better patient outcomes in complex breast reconstruction.

Regional Blocks Benefit Patients Undergoing Bilateral Mastectomy with Immediate Implant-Based Reconstruction, Even After Discharge.

BACKGROUND: There is limited evidence that regional anesthesia reduces pain in patients undergoing mastectomy with immediate implant-based reconstruction. We sought to determine whether regional blocks reduce opioid consumption and improve post-discharge patient-reported pain in this population. METHODS: We retrospectively reviewed patients who underwent bilateral mastectomy with immediate implant-based reconstruction with and without a regional block. We tested for differences in opioid consumption by block receipt using multivariable ordinal regression, and also assessed routinely collected patient-reported outcomes (PROs) for 10 days postoperatively and tested the association between block receipt and moderate or greater pain. RESULTS: Of 754 patients, 89% received a block. Non-block patients had an increase in the odds of requiring a higher quartile of postoperative opioids. Among block patients, the estimated probability of being in the lowest quartile of opioids required was 25%, compared with 15% for non-block patients. Odds of patient-reported moderate or greater pain after discharge was 0.54 times lower in block patients than non-block patients (p = 0.025). Block patients had a 49% risk of moderate or greater pain compared with 64% in non-block patients on postoperative day 5. There was no indication of any reason for these differences other than a causal effect of the block. CONCLUSION: Receipt of a regional block resulted in reduced opioid use and lower risk of self-reported moderate and higher pain after discharge in bilateral mastectomy with immediate implant-based reconstruction patients. Our use of PROs suggests that the analgesic effects of blocks persist after discharge, beyond the expected duration of a 'single shot' block.

Growing pains: strategies for improving ergonomics in minimally invasive gynecologic surgery.

PURPOSE OF REVIEW: To evaluate factors contributing to the development of work-related musculoskeletal disorders (WMSDs) and review strategies for mitigating ergonomic strain in minimally invasive gynecologic surgery. RECENT FINDINGS: Factors associated with increased ergonomic strain and the development of WMSDs include increasing patient body mass index (BMI), smaller surgeon hand size, noninclusive design of instruments and energy devices and improper positioning of surgical equipment. Each type of minimally invasive surgery (laparoscopic, robotic, vaginal) confers its own ergonomic risk to the surgeon. Recommendations have been published regarding optimal ergonomic surgeon and equipment positioning. Intraoperative breaks and stretching are effective in reducing surgeon discomfort. Formal training in ergonomics has not yet been widely implemented, but educational interventions have been effective in reducing surgeon discomfort and can improve surgeon recognition of suboptimal ergonomics. SUMMARY: Considering the serious downstream effects of WMSDs on surgeons, it is imperative to implement strategies for WMSD prevention. Optimal positioning of the surgeons and operative equipment should be routine. Intraoperative breaks and stretching should be incorporated during procedures and between every case. Formal education in ergonomics should be provided to surgeons and trainees. Additionally, more inclusive instrument design by industry partners should be prioritized.

Practice Patterns and Outcomes of Patients With Retained Gastric Food Content Encountered During Endoscopy.

INTRODUCTION: Retained gastric food content encountered during upper endoscopy may reduce diagnostic accuracy and increase the risk of aspiration. The aim of this study was to evaluate endoscopists' practice patterns and clinical outcomes in patients with retained gastric food content encountered during endoscopy. METHODS: Consecutive patients with retained gastric food content during first-time endoscopy at Loma Linda University Health (January 2016-March 2021) were identified. Primary endpoints were a complete examination (deep duodenal intubation) and 30-day postprocedural respiratory adverse events. RESULTS: Of 17,868 patients undergoing endoscopy, 629 (3.5%) (mean age 55 ± 17 years) met inclusion criteria. Moderate sedation was performed in 506 (80.4%), anesthesiologist-assisted sedation in 16 (2.5%), and general anesthesia in 107 (17.0%) patients. 534 (84.9%) patients received a complete examination, and endoscopist-specific completion rates varied by quintile among 26 endoscopists (range 70.3%-98.0%, P < 0.0001). Large food gastric content decreased (adjusted odds ratio [aOR] 0.3, 95% confidence interval [CI] 0.2-0.4) while obtaining mucosal biopsies increased (aOR 2.5, 95% CI 1.4-4.7) the likelihood of complete examination after adjusting for endoscopist-specific completion rates. Subsequently, 58 (9.2%) patients required repeat endoscopy within 30 days. During follow-up, 41 (6.5%) patients developed respiratory adverse events including 21 (3.3%) requiring ventilatory support. Hospitalized patients (aOR 37.8, 95% CI 4.9-289.0) compared with outpatients and large compared with small gastric food content (aOR 2.1, 95% CI 1.1-4.2) increased the likelihood of respiratory adverse events. DISCUSSION: Although deep duodenal intubation was achieved in most patients receiving endoscopy, the rate of complete examination varied among individual endoscopists and the extent of food burden. Respiratory adverse events occurred almost exclusively in hospitalized patients and were associated with high morbidity including half developing respiratory failure.

Associations of influenza vaccination with severity of immune-related adverse events in patients with advanced thoracic cancers on immune checkpoint inhibitors.

Background: Whether influenza vaccination (FV) is associated with the severity of immune-related adverse events (IRAEs) in patients with advanced thoracic cancer on immune checkpoint inhibitors (ICIs) is not fully understood. Methods: Patients enrolled in this retrospective cohort study were identified from the Vanderbilt BioVU database and their medical records were reviewed. Patients with advanced thoracic cancer who received FV within 3 months prior to or during their ICI treatment period were enrolled in the FV-positive cohort and those who did not were enrolled in the FV-negative cohort. The primary objective was to detect whether FV is associated with decreased IRAE severity. The secondary objectives were to evaluate whether FV is associated with a decreased risk for grade 3-5 IRAEs and better survival times. Multivariable ordinal logistic regression was used for the primary analysis. Results: A total of 142 and 105 patients were enrolled in the FV-positive and FV-negative cohorts, respectively. There was no statistically significant difference in patient demographics or cumulative incidences of IRAEs between the two cohorts. In the primary analysis, FV was inversely associated with the severity of IRAEs (OR 0.63; p=0.046). In the secondary analysis, FV was associated with a decreased risk for grade 3-5 IRAEs (OR 0.42; p=0.005). Multivariable Cox regression showed that FV was not associated with survival times. Conclusions: Our study showed that FV does not increase toxicity for patients with advanced thoracic cancer on ICIs and is associated with a decreased risk for grade 3-5 IRAEs. No statistically significant survival differences were found between patients with and without FV.

Cox Proportional Hazard Ratios Overestimate Survival Benefit of Immune Checkpoint Inhibitors: Cox-TEL Adjustment and Meta-Analyses of Programmed Death-Ligand 1 Expression and Immune Checkpoint Inhibitor Survival Benefit.

INTRODUCTION: Survival benefit of immune checkpoint inhibitor (ICI) therapy in lung cancer is not fully understood. METHODS: PubMed-cataloged publications through February 14, 2022, were queried for randomized controlled trials of ICI in lung cancer, and identified publications were reviewed for inclusion. Reported Cox hazard ratios (HRs) for overall survival were transformed to Cox-TEL HR for ICI short-term survivors (ST-HR) and difference in proportions for patients with long-term survival (LT-DP). Meta-analyses were performed using a frequentist random-effect model. Outcomes of interest were pooled overall survival Cox HR, ST-HR, and LT-DP in NSCLC, stratified by programmed death-ligand 1 (PD-L1) level (primary outcome) and ICI treatment line (secondary). RESULTS: A total of nine publications representing eight clinical trials were selected for meta-analysis. Primary analysis yielded the following metrics for patients with PD-L1 expression less than 1%, more than or equal to 1%, and more than or equal to 50%, respectively: pooled Cox HR, 0.71 (95% confidence interval [CI]: 0.62-0.82), 0.74 (95% CI: 0.68-0.82), and 0.62 (95% CI: 0.54-0.70); pooled ST-HR, 0.91 (95% CI: 0.79-1.05), 0.88 (95% CI: 0.82-0.94), and 0.70 (95% CI: 0.60-0.83); and pooled LT-DP, 0.10 (95% CI: 0.00-0.20), 0.09 (95% CI: 0.06-0.12), and 0.11 (95% CI: 0.05-0.17). Results of secondary analysis revealed LT-DP of approximately 10% across treatment lines. CONCLUSIONS: This study reveals an approximately 10% long-term survival probability increment in ICI long-term survivors across PD-L1-positive subpopulations in both ICI treatment lines. Furthermore, ST-HR was consistently poorer than Cox HR. For patients with PD-L1 less than 1%, neither LT-DP nor ST-HR achieved statistical significance. The analysis provides greater insight into the treatment effect of ICI in published trials.

Analysis of Cancer Survival Associated With Immune Checkpoint Inhibitors After Statistical Adjustment: A Systematic Review and Meta-analyses.

Importance: Appropriate clinical decision-making relies on accurate data interpretation, which in turn relies on the use of suitable statistical models. Long tails and early crossover-2 features commonly observed in immune checkpoint inhibitor (ICI) survival curves-raise questions as to the suitability of Cox proportional hazards regression for ICI survival analysis. Cox proportional hazards-Taylor expansion adjustment for long-term survival data (Cox-TEL) adjustment may provide possible solutions in this setting. Objective: To estimate overall survival and progression-free survival benefits of ICI therapy vs chemotherapy using Cox-TEL adjustment. Data Sources: A PubMed search was performed for all cataloged publications through May 22, 2022. Study Selection: The search was restricted to randomized clinical trials with search terms for ICIs and lung cancer, melanoma, or urothelial carcinoma. The publications identified were further reviewed for inclusion. Data Extraction and Synthesis: Cox proportional hazards ratios (HRs) were transformed to Cox-TEL HRs for patients with short-term treatment response (ie, short-term survivor) (ST-HR) and difference in proportions for patients with long-term survival (LT-DP) by Cox-TEL. Meta-analyses were performed using a frequentist random-effects model. Main Outcomes and Measures: Outcomes of interest were pooled overall survival (primary outcome) and progression-free survival (secondary outcome) HRs, ST-HRs, and LT-DPs. Subgroup analyses stratified by cancer type also were performed. Results: A total of 1036 publications was identified. After 3 levels of review against inclusion criteria, 13 clinical trials (7 in non-small cell lung cancer, 3 in melanoma, and 3 in urothelial carcinoma) were selected for the meta-analysis. In the primary analysis, pooled findings were 0.75 (95% CI, 0.70-0.81) for HR, 0.86 (95% CI, 0.81-0.92) for ST-HR, and 0.08 (95% CI, 0.06-0.10) for LT-DP. In the secondary analysis, the pooled values for progression-free survival were 0.77 (95% CI, 0.64-0.91) for HR, 1.02 (95% CI, 0.84-1.24) for ST-HR, and 0.10 (95% CI, 0.06-0.14) for LT-DP. Conclusions and Relevance: This systematic review and meta-analysis of ICI clinical trial results noted consistently larger ST-HRs vs Cox HRs for ICI therapy, with an LT-DP of approximately 10%. These results suggest that Cox HRs may not provide a full picture of survival outcomes when the risk reduction from treatment is not constant, which may aid in the decision-making process of oncologists and patients.

Porto-Sinusoidal Vascular Disease in a Patient With Diffuse Aortitis and Massive Ascites.

A 69-year-old man with no history of liver disease presented with massive ascites. Imaging demonstrated diffuse wall thickening of the entire aorta, renal pelvis, and ureters along with an enlarged main portal vein, portosystemic collaterals, and peritoneal thickening concerning for large vessel vasculitis. Liver biopsy was consistent with obliterative portal venopathy. The patient was started on corticosteroid therapy with improvement in his ascites. This case study reveals a rare association between vasculitis and portal-sinusoidal vascular disease and idiopathic non-cirrhotic portal hypertension, highlighting the heterogenous clinical presentation of this disease entity.

The Impact of Androgen Deprivation Therapy on COVID-19 Illness in Men With Prostate Cancer.

BACKGROUND: TMPRSS2, a cell surface protease regulated by androgens and commonly upregulated in prostate cancer (PCa), is a necessary component for SARS-CoV-2 viral entry into respiratory epithelial cells. Previous reports suggested a lower risk of SARS-CoV-2 among PCa patients on androgen deprivation therapy (ADT). However, the impact of ADT on severe COVID-19 illness is poorly understood. METHODS: We performed a multicenter study across 7 US medical centers and evaluated patients with PCa and SARS-CoV-2 detected by polymerase-chain-reaction between March 1, 2020, and May 31, 2020. PCa patients were considered on ADT if they had received appropriate ADT treatment within 6 months of COVID-19 diagnosis. We used multivariable logistic and Cox proportional-hazard regression models for analysis. All statistical tests were 2-sided. RESULTS: We identified 465 PCa patients (median age = 71 years) with a median follow-up of 60 days. Age, body mass index, cardiovascular comorbidity, and PCa clinical disease state adjusted overall survival (hazard ratio [HR] = 1.16, 95% confidence interval [CI] = 0.68 to 1.98, P = .59), hospitalization status (HR = 0.96, 95% CI = 0.52 to 1.77, P = .90), supplemental oxygenation (HR 1.14, 95% CI = 0.66 to 1.99, P = .64), and use of mechanical ventilation (HR = 0.81, 95% CI = 0.25 to 2.66, P = .73) were similar between ADT and non-ADT cohorts. Similarly, the addition of androgen receptor-directed therapy within 30 days of COVID-19 diagnosis to ADT vs ADT alone did not statistically significantly affect overall survival (androgen receptor-directed therapy: HR = 1.27, 95% CI = 0.69 to 2.32, P = .44). CONCLUSIONS: In this retrospective cohort of PCa patients, the use of ADT was not demonstrated to influence severe COVID-19 outcomes, as defined by hospitalization, supplemental oxygen use, or death. Age 70 years and older was statistically significantly associated with a higher risk of developing severe COVID-19 disease.

Enhanced Recovery After Surgery in Minimally Invasive Gynecologic Surgery.

Enhanced recovery after surgery (ERAS) is a multimodal, multidisciplinary approach to optimize patient outcomes by minimizing surgical stress with the goal of returning to normal physiologic function. Using minimally invasive surgery as the preferred route for gynecologic surgery is an integral component of ERAS and is strongly correlated with improved postoperative outcomes. Implementation of ERAS programs in minimally invasive gynecologic surgery results in substantial improvements in clinical outcomes with higher rates of same-day discharge, reduction in postoperative nausea and vomiting, improved patient satisfaction, and decreased opioid consumption without increase in complications, readmissions, or health care costs.

Combined coronary artery bypass graft and liver/kidney transplantation in a liver failure patient with acute on chronic kidney failure and antiphospholipid syndrome.

Coexisting coronary artery disease (CAD), end-stage liver disease (ESLD), renal failure, and hypercoagulable state poses a formidable clinical challenge. Here, we discuss the first known case of a patient with antiphospholipid syndrome (APLS), ESLD complicated by hepatorenal syndrome (HRS), and severe CAD who successfully underwent combined coronary artery bypass grafting (CABG) and simultaneous liver/kidney (SLK) transplant.

Cumulative summation analysis of learning curve for robotic-assisted hiatal hernia repairs.

BACKGROUND: Robotic-assisted laparoscopic surgery (RALS) is evolving as an important surgical approach in the field of general surgery. We aimed to evaluate the learning curve for RALS procedures involving repair of hiatal hernias. METHODS: A series of robotic-assisted hiatal hernia (HH) repairs were performed between 2013 and 2017 by a surgeon at a single institution. Data were entered into a retrospective database. Patient demographics and intraoperative parameters including console time (CT), surgery time (ST), and total operative time (OT) were examined and abstracted for learning curve analysis using the cumulative sum (CUSUM) method. Assessment of perioperative and post-operative outcomes were calculated using descriptive statistics. RESULTS: The average age of the patients was 57.4 years, average BMI was 29.9 kg/m2, median American Society of Anesthesiologists (ASA) classification was 2, and average Charlson Comorbidity Index (CCI) score was 2.8. The series had a mean CT of 132.6 min, mean ST of 145.1 min, and mean OT of 197.4 min. The CUSUM learning curve for CT was best approximated as a third-order polynomial consisting of three unique phases: the initial training phase (case 1-40), the improvement phase (case 41-85), and the mastery phase (case 86 onwards). There was no significant difference in perioperative complications between the phases. Short-term clinical outcomes were comparable with national standards and did not correlate significantly with operative experience. CONCLUSIONS: The three phases identified with CUSUM analysis represented characteristic stages of the learning curve for robotic hiatal hernia procedures. Our data suggest the training phase is achieved after 40 cases and a high level of mastery is achieved after approximately 85 cases. Thus, the CUSUM method serves as a useful tool for objectively evaluating practical skills for surgeons and can ultimately help establish milestones that assess surgical competency during robotic surgery training.

The Cost of Guideline Adherence: A Multicenter Analysis of the Financial Implications of Adopting the US Multi-Society Task Force Polypectomy Guidelines.

GOAL: The goal of this study was to determine the financial impact of adopting the US Multi-Society Task Force (USMSTF) polypectomy guidelines on physician reimbursement and disposable equipment costs for gastroenterologists in the academic medical center and community practice settings. BACKGROUND: In 2020, USMSTF guidelines on polypectomy were introduced with a strong recommendation for cold snare rather than cold forceps technique for removing diminutive and small polyps. Polypectomy with snare technique reimburses physicians at a higher rate compared with cold forceps and also requires different disposable equipment. The financial implications of adopting these guidelines is unknown. MATERIALS AND METHODS: Patients that underwent screening colonoscopy where polypectomy was performed at an academic medical center (Loma Linda University Medical Center) and community practice medical center (Ascension Providence Hospital) between July 2018 and July 2019 were identified. The polypectomy technique performed during each procedure was determined (forceps alone, snare alone, forceps plus snare) along with the number and size of polyps as well as disposable equipment. Actual and projected provider reimbursement and disposable equipment costs were determined based on applying the new polypectomy guidelines. RESULTS: A total of 1167 patients underwent colonoscopy with polypectomy. Adhering to new guidelines would increase estimated physician reimbursement by 5.6% and 12.5% at academic and community practice sites, respectively. The mean increase in physician reimbursement per procedure was significantly higher at community practice compared with the academic setting ($29.50 vs. $14.13, P <0.00001). The mean increase in disposable equipment cost per procedure was significantly higher at the community practice setting ($6.11 vs. $1.97, P <0.00001). CONCLUSION: Adopting new polypectomy guidelines will increase physician reimbursement and equipment costs when colonoscopy with polypectomy is performed.

Precision medicine in trauma: a transformational frontier in patient care, education, and research.

PURPOSE: Trauma is the leading cause of death before the age of 45 in the United States. Precision medicine (PM) is the most advanced scientific form of medical practice and seeks to gather data from the genome, environmental interactions, and lifestyles. Relating to trauma, PM promises to significantly advance our understanding of the factors that contribute to the physiologic response to injury. METHODS: We review the status of PM-driven trauma care. Semantic-based methods were used to gather data on genetic/epigenetic variability previously linked to the principal causes of trauma-related outcomes. Data were curated to include human investigations involving genomics/epigenomics with clinical relevance identifiable early after injury. RESULTS: Most studies relevant to genomic/epigenomic differences in trauma are specific to traumatic brain injury and injury-related sepsis. Genomic/epigenomic differences rarely encompass other relevant factors, such as coagulability and pharmacogenomics. Few studies describe clinical use of genomics/epigenomics for therapeutic intervention in trauma care, and even fewer attempt to incorporate real-time genomic/epigenomic information to precisely guide clinical decision-making. CONCLUSION: Considering that genomics/epigenomics, environmental exposures, and lifestyles are most likely to be of significant medical relevance in advancing the field of trauma, the lack of application of concepts and methodologies from PM to trauma education, research, practice, and community wellness is underwhelming. We suggest that significant effort be given to incorporate the tools of what is becoming the "new medicine".

Inositol serves as a natural inhibitor of mitochondrial fission by directly targeting AMPK.

Mitochondrial dynamics regulated by mitochondrial fusion and fission maintain mitochondrial functions, whose alterations underline various human diseases. Here, we show that inositol is a critical metabolite directly restricting AMPK-dependent mitochondrial fission independently of its classical mode as a precursor for phosphoinositide generation. Inositol decline by IMPA1/2 deficiency elicits AMPK activation and mitochondrial fission without affecting ATP level, whereas inositol accumulation prevents AMPK-dependent mitochondrial fission. Metabolic stress or mitochondrial damage causes inositol decline in cells and mice to elicit AMPK-dependent mitochondrial fission. Inositol directly binds to AMPKγ and competes with AMP for AMPKγ binding, leading to restriction of AMPK activation and mitochondrial fission. Our study suggests that the AMP/inositol ratio is a critical determinant for AMPK activation and establishes a model in which AMPK activation requires inositol decline to release AMPKγ for AMP binding. Hence, AMPK is an inositol sensor, whose inactivation by inositol serves as a mechanism to restrict mitochondrial fission.