Assessing and harnessing updated polyketide synthase modules through combinatorial engineering.

The modular nature of polyketide assembly lines and the significance of their products make them prime targets for combinatorial engineering. While short synthases constructed using the recently updated module boundary have been shown to outperform those using the traditional boundary, larger synthases constructed using the updated boundary have not been investigated. Here we describe our design and implementation of a BioBricks-like platform to rapidly construct 5 triketide, 25 tetraketide, and 125 pentaketide synthases from the updated modules of the Pikromycin synthase. Every combinatorial possibility of modules 2-6 inserted between the first and last modules of the native synthase was constructed and assayed. Anticipated products were observed from 60% of the triketide synthases, 32% of the tetraketide synthases, and 6.4% of the pentaketide synthases. Ketosynthase gatekeeping and module-skipping were determined to be the principal impediments to obtaining functional synthases. The platform was also used to create functional hybrid synthases through the incorporation of modules from the Erythromycin, Spinosyn, and Rapamycin assembly lines. The relaxed gatekeeping observed from a ketosynthase in the Rapamycin synthase is especially encouraging in the quest to produce designer polyketides.

Ropivacaine-Epinephrine-Clonidine-Ketorolac Cocktail as a Local Anesthetic for Lumbar Decompression Surgery: A Single Institutional Experience.

OBJECTIVE: The goal of this study is to discuss our initial experience with a multimodal opioid-sparing cocktail containing ropivacaine, epinephrine, clonidine, and ketorolac (RECK) in the postoperative management of lumbar decompression surgeries. METHODS: Patients were either administered no local anesthetic at the incision site or were administered a weight-based amount of RECK into the paraspinal musculature and subdermal space surrounding the operative site once the fascia was closed. We performed a retrospective chart review of all patients 18 years of age or older undergoing lumbar laminectomy and lumbar diskectomy surgeries between December 2019 and April 2021. Outcomes including total opioid use, measured as morphine milligram equivalent, length of stay, and postoperative visual analog scores for pain, were collected. Relationships between variables were analyzed with Student's t-test, chi-square tests, and Fisher exact tests. RESULTS: A total of 121 patients undergoing 52 lumbar laminectomy and 69 lumbar diskectomy surgeries were identified. For lumbar laminectomy, patients who were administered RECK had decreased opioid use in the postoperative period (11.47 ± 12.32 vs. 78.51 ± 106.10 morphine milligram equivalents, P = 0.019). For patients undergoing lumbar diskectomies, RECK administration led to a shorter length of stay (0.17 ± 0.51 vs. 0.79 ± 1.45 days, P = 0.019) and a lower 2-hour postoperative pain score (3.69 ± 2.56 vs. 5.41 ± 2.28, P = 0.006). CONCLUSIONS: The RECK cocktail has potential to be an effective therapeutic option for the postoperative management of lumbar decompression surgeries.

Treatment of unilateral L5-S1 locked facet in a pediatric patient.

Background: Traumatic unilateral lumbosacral facet dislocations are rare injuries. The majority of cases are treated with open reduction and instrumented spinal fusions. Only less commonly can they be managed conservatively. Case Description: A 7-year-old unrestrained passenger was involved in a high-speed motor vehicle accident. X-ray/magnetic resonance/computed tomography imaging documented a unilateral L5-S1 facet dislocation and multiple lumbar/sacral fractures. The patient underwent open reduction and temporary L5-pelvic instrumentation without fusion; the instrumentation was removed 10 weeks later at which point follow-up imaging showed preserved lumbosacral stability. Conclusion: Open reduction with temporary instrumentation without fusion was successfully utilized to treat a unilateral L5-S1 facet dislocation in a 7-year-old child.

Surgical Aortic Valve Replacement to Treat Prosthetic Valve Endocarditis After Valve-in-Valve Transcatheter Aortic Valve Replacement.

Prosthetic valve endocarditis (PVE) is an uncommon complication after heart valve replacement surgery that can result in increased morbidity and mortality. Current guidelines for management of PVE recommend antibiotic therapy followed by surgical valve replacement. The number of aortic valve replacements is expected to rise in the coming years with the expanded indications for use of transcatheter aortic valve replacement (TAVR) in patients with low, intermediate, and high surgical risk, as well as in patients with a failed aortic bioprosthetic valve. Current guidelines do not address the use of valve-in-valve (ViV) TAVR for management of PVE in patients who are at high risk for surgical intervention. The authors present a case of a patient with aortic valve PVE after surgical aortic valve replacement (SAVR); he was treated with valve-in-valve (ViV) TAVR due to the high surgical risk. The patient was discharged, but he returned to the hospital with PVE and valve dehiscence 14 months after ViV TAVR, after which he successfully underwent re-operative SAVR.

Superficial Parasternal Intercostal Plane Blocks (SPIB) With Buprenorphine, Magnesium, and Bupivacaine for Management of Pain in Coronary Artery Bypass Grafting.

Introduction Management of post-operative pain after cardiac surgery continues to be a challenge; inadequate management of pain can lead to increased morbidity, impaired physical function with potential delay in recovery, increased perioperative and chronic opioid consumption, increased cost of care, and a decreased quality of life. This study aimed to evaluate the effect of adding buprenorphine and magnesium to bupivacaine for superficial parasternal intercostal plane blocks (SPIB) on pain and opioid consumption in the first 24 hours after coronary artery bypass grafting (CABG). Methods Patients undergoing CABG were divided into the following four groups: saline SPIB, SPIB with bupivacaine (BPVC), SPIB with bupivacaine and buprenorphine (BPVC+BPRN), and SPIB with bupivacaine, buprenorphine, and magnesium (BPVC+BPRN+MG). The primary outcomes were pain scores and opioid consumption after SPIB; the secondary outcomes were post-operative nausea and vomiting, time to extubation, and length of stay (LOS) in the intensive care unit and hospital. Results One hundred thirty-four eligible patients undergoing CABG were randomized to either the saline (n=27), BPVC (n=20), BPVC+BPRN (n=24), or BPVC+BPRN+MG (n=29) group. All of the intervention groups combined (BPVC, BPVC+BPRN, and BPVC+BPRN+MG) had decreased pain scores and decreased opioid consumption when compared to the saline group; although not statistically significant, visual analog scale (VAS) scores trended downward at most time points with BPVC versus saline, BPVC+BPRN versus BPVC, and BPVC+BPRN+MG versus BPVC+BPRN. There was no difference among the study groups in the incidence of post-operative nausea and/or vomiting (PONV), time to extubation, hospital LOS, and ICU LOS. Conclusion In this prospective, double-blind, placebo-controlled trial, we found that SPIB with local anesthetic is effective at reducing VAS scores and opioid consumption after CABG. Further study is needed to determine whether the addition of adjuvants can further improve pain control and opioid consumption.

Postoperative Cognitive Dysfunction in the Elderly: A Role for Modafinil.

Introductionː Postoperative cognitive dysfunction has long-term consequences of increased mortality, loss of autonomy, and prolonged hospitalization. We sought to determine whether exposing patients to modafinil may attenuate or prevent this devastating syndrome from affecting the elderly postoperatively. Methodsː Adults aged 65 and older and American Society of Anesthesiologists (ASA) I-III physical status scheduled for elective noncardiac/non-neurosurgical surgery were included. Subjects were tested with the Trail Making Test (TMT) and Rey Auditory Visual Learning Test (RAVLT) preoperatively as well as in the immediate postoperative period, at 1 week, and at 3 months. After baseline testing, patients were randomized into three groups: 0) placebo pre and post-procedure; 1) modafinil only pre-procedure and placebo post-procedure; and 2) modafinil pre and post-procedure. A nonsurgical control group was also utilized. Resultsː Seventy-six subjects completed the trial 3 months post-surgery. The baseline RAVLT obtained was analyzed with 2-way ANOVA with repeated measures and showed improvement in learning in all groups (p = 0.03). At 1-week post-surgery, Group 0 subjects demonstrated no learning improvement in the RAVLT. However, there was a significant improvement in learning in both groups that received modafinil (p<0.01), and in the nonsurgical controls (p<0.01). This learning benefit normalized at 3 months. Conclusionː In this prospective, double-blind, placebo-controlled trial, we found that patients who received modafinil showed improvement in the RAVLT at 1 week. However, this learning benefit normalized at 3 months. Further study should examine dose effect, timing, and route of administration to determine if the effect can be enhanced and if in fact, wakefulness is improved post-surgically.

Adductor Canal Blocks With Bupivacaine and Magnesium After Same-day Discharge Total Knee Arthroplasty Improve Postoperative Pain Relief and Decrease Opioid Consumption: A Prospective Randomized Controlled Trial.

OBJECTIVES: Adequate pain management is a critical component of facilitating same-day discharge for total knee arthroplasty (TKA). Adductor canal blocks (ACB) have been shown to be an effective technique for managing pain after TKA. The objective of this study was to investigate the impact of adding magnesium to local anesthetic in ACB on postoperative pain, opioid consumption, nausea, and overall patient satisfaction. MATERIALS AND METHODS: A sample of 119 adults undergoing elective unilateral TKA were included. Patients were randomly assigned to receive ACB with magnesium and bupivacaine (n=56) or with bupivacaine only (n=63). Primary outcomes were total opioid consumption in the first 48 hours after surgery and pain scores. Secondary outcomes were the incidence of nausea in the first 48 hours after surgery and total overall satisfaction. RESULTS: Opioid consumption decreased significantly in the Mg group compared with the no-Mg group over the first 24 hours (33.2±3.0 vs. 21.3±2.4, P=0.003), the second 24 hours (35.4±2.7 vs. 27.3±2.3, P=0.026), and the first 48 hours total after surgery (68.6±5.1 vs. 48.6±4.3, P=0.004). Pain scores were reduced in the Mg group (24 h: 5.1±2.3 vs. 3.5±2.0, P=0.000; 48 h: 5.1±1.6 vs. 3.9±1.6, P=0.000). Secondary outcomes showed no difference in the incidence of nausea over the first 48 hours and overall satisfaction. CONCLUSION: The addition of magnesium to local anesthetic in ACB decreases pain scores and opioid consumption, without increasing nausea, when compared with ACB with local anesthetic alone.

Complications of Transesophageal Echocardiography: A Review of Injuries, Risk Factors, and Management.

Transesophageal echocardiography (TEE) use has become widespread in cardiac surgical operating rooms over the last 2 decades. Surgical and medical decision-making often are guided by the findings of the TEE examination, rendering TEE an invaluable tool both inside and outside the operating room. TEE has become ubiquitous in some parts because it is considered safe and relatively noninvasive. However, it is imperative for clinicians to understand that TEE can cause severe and possibly life-threatening complications, and the risks of TEE must be balanced against its benefits as a diagnostic tool. Upper gastrointestinal (UGI) injuries are the most commonly described complications of TEE; however, the relative infrequency of injuries and lack of uniform reporting make it difficult to definitively identify potential risk factors. Some large retrospective trials suggested that patient factors (age, body mass index, anatomic abnormalities), comorbid conditions (previous stroke), and procedural variables (procedure time, cardiopulmonary bypass time, etc.) are associated with TEE-related injuries. In this narrative review of complications from TEE, the authors focus on the incidence of UGI injuries, the spectrum of injuries associated with TEE, risk factors that may contribute to UGI injuries, as well as diagnosis and management options. Lastly, the discussion focuses on the prevention of injuries as TEE use continues to become more prevalent.

Functional Tricuspid Regurgitation in Patients With Chronic Mitral Regurgitation: An Evidence-Based Narrative Review.

Chronic mitral regurgitation leads to a series of downstream pathologic changes, including pulmonary hypertension, right ventricular dilation, tricuspid leaflet tethering, and tricuspid annular dilation, which can result in functional tricuspid regurgitation (FTR). The five-year survival rate for patients with severe FTR is reported to be as low as 34%. While FTR was often left uncorrected during left-heart valvular surgery, under the assumption that correction of the left-sided lesion would reverse the right-heart changes that cause FTR, recent data largely have supported concomitant tricuspid valve repair at the time of mitral surgery. In this review, the authors discuss the potentially irreversible nature of the changes leading to FTR, the likelihood of progression of FTR after mitral surgery, and the evidence for and against concomitant tricuspid valve repair at the time of mitral valve intervention. Lastly, this narrative review also examines advances in transcatheter therapies for the tricuspid valve and the evidence behind concomitant transcatheter tricuspid repair at the time of transcatheter mitral repair.

Blunt Trauma to the Heart: A Review of Pathophysiology and Current Management.

Blunt cardiac injury (BCI), defined as an injury to the heart from blunt force trauma, ranges from minor to life-threatening. The majority of BCIs are due to motor vehicle accidents; however, injuries caused by falls, blasts, and sports-related injuries also can be sources of BCI. A significant proportion of patients with BCI do not survive long enough to receive medical care, succumbing to their injuries at the scene of the accident. Additionally, patients with blunt trauma often have coexisting injuries (brain, spine, orthopedic) that can obscure the clinical picture; therefore, a high degree of suspicion often is required to diagnose BCI. Traditionally, hemodynamically stable injuries suspicious for BCI have been evaluated with electrocardiograms and chest radiographs, whereas hemodynamically unstable BCIs have received operative intervention. More recently, computed tomography and echocardiography increasingly have been utilized to identify injuries more rapidly in hemodynamically unstable patients. Transesophageal echocardiography can play an important role in the diagnosis and management of several BCIs that require operative repair. Close communication with the surgical team and access to blood products for potentially massive transfusion also play key roles in maintaining hemodynamic stability. With proper surgical and anesthetic care, survival in cases involving urgent cardiac repair can reach 66%-to-75%. This narrative review focuses on the types of cardiac injuries that are caused by blunt chest trauma, the modalities and techniques currently used to diagnose BCI, and the perioperative management of injuries that require surgical correction.

Sacral Dysmorphism Increases the Risk of Superior Gluteal Artery Injury in Percutaneous Sacroiliac Joint Fusion: Case Report and Literature Review.

Sacroiliac (SI) joint dysfunction is a significant contributor to low back pain. Percutaneous SI joint fusion is a minimally invasive procedure that can provide excellent pain relief for patients, but it is not without complications, especially in patients with abnormal lumbosacral anatomy. We report the case of a 71-year-old man with sacral dysmorphism who had a painful SI joint that was refractory to conservative therapy. After undergoing an elective percutaneous SI joint fusion, he was discharged in stable condition. He returned in a delayed fashion with a large subgluteal hematoma. Imaging revealed disruption of a branch of the superior gluteal artery (SGA). Surgical exploration and ligation of the SGA were undertaken. Sacral dysmorphism affects SI joint fusion procedures by altering sacral anatomy and the safe zones for SI joint implants. Variations in lumbosacral anatomy can also alter the course of the SGA and adjacent nerves. Due to the wide prevalence of sacral dysmorphism, especially in the setting of low back pain, pre-surgical planning to avoid iatrogenic injuries must be considered with advanced imaging studies such as a computed tomography angiogram of the pelvis or catheter-based angiogram, or alternative surgical approaches to the SI joint must be taken.