Results From a Prospective, Clinical Study (US-nPower) Evaluating a Miniature Spinal Cord Stimulator for the Management of Chronic, Intractable Pain.

BACKGROUND: Chronic, intractable, neuropathic pain is readily treatable with spinal cord stimulation (SCS). Technological advancements, including device miniaturization, are advancing the field of neuromodulation. OBJECTIVES: We report here the results of an SCS clinical trial to treat chronic, low back and leg pain, with a micro-implantable pulse generator (micro-IPG). STUDY DESIGN: This was a single-arm, prospective, multicenter, postmarket, observational study. SETTING: Patients were recruited from 15 US-based comprehensive pain centers. METHODS: This open-label clinical trial was designed to evaluate the performance of the Nalu™ Neurostimulation System (Nalu Medical, Inc., Carlsbad, CA) in the treatment of low back and leg pain. Patients, who provided informed consent and were successfully screened for study entry, were implanted with temporary trial leads. Patients went on to receive a permanent implant of the leads and micro-IPG if they demonstrated a >= 50% reduction in pain during the temporary trial period. Patient-reported outcomes (PROs), such as pain scores, functional disability, mood, patient impression of change, comfort, therapy use profile, and device ease of use, were captured. RESULTS: At baseline, the average pain Visual Analog Scale (VAS) score was 72.1 ± 17.9 in the leg and 78.0 ± 15.4 in the low back. At 90 days following permanent implant (end of study), pain scores improved by 76% (VAS 18.5 ± 18.8) in the leg and 75% (VAS 19.7 ± 20.8) in the low back. Eighty-six percent  of both leg pain and low back pain patients demonstrated a >= 50% reduction in pain at 90 days following implant. The comfort of the external wearable (Therapy Disc and Adhesive Clip) was rated 1.16 ± 1.53, on average, at 90 days on an 11-point rating scale (0 = very comfortable, 10 = very uncomfortable). All PROs demonstrated statistically significant symptomatic improvement at 90 days following implant of the micro-IPG. LIMITATIONS:   Limitations of this study include the lack of long-term results (beyond 90 days) and a relatively small sample size of 35 patients who were part of the analysis; additionally, there was no control arm or randomization as this was a single-arm study, without a comparator, designed to document the efficacy and safety of the device. Therefore, no direct comparisons to other SCS systems were possible. CONCLUSIONS: This clinical study demonstrated profound leg and low back pain relief in terms of overall pain reduction, as well as the proportion of therapy responders. The study patients reported the wearable aspects of the system to be very comfortable.

Postoperative statin therapy is not associated with reduced incidence of venous thromboembolic events following kidney transplantation.

BACKGROUND: The pleiotropic effects of statin therapy on inflammation and coagulation may reduce the risk of venous thromboembolism. This study evaluated whether statin therapy is associated with decreased venous thromboembolic (VTE) events following kidney transplantation. METHODS: We performed a retrospective analysis of all primary kidney transplants performed between January 2014 and December 2019 at Mayo Clinic Arizona. Patients were divided into two groups depending on sustained statin therapy during the first year following transplantation. Recipient and donor clinical and demographic data were collected. The primary outcome was admission for symptomatic VTE events (deep vein thrombosis [DVT] or pulmonary embolism [PE]). RESULTS: Sustained statin therapy in the first year following transplant was observed in 16.1% (n = 223) of 1384 kidney transplants. The overall incidence of VTE events in the year following kidney transplant was 3.8%. VTE occurred in 4.1% of recipients treated with statins and 3.8% of the controls - (hazard ratio [HR] .92, 95% confidence interval [95% CI] .39, 2.21, p = .86). However, there were significant differences between the groups in terms of age, sex, race/ethnicity, body mass index, indication for transplant, diagnosis of diabetes and discharge antiplatelet or anticoagulant therapy. Following sensitivity analysis in which cohort matching was performed to account for these differences, there was no difference in VTE event-free survival (HR .89, 95% CI .41, 1.96, p = .78) or overall survival (HR .54, 95% CI .15, 1.94, p = .35) between patients treated with statins compared to controls. CONCLUSION: Statin therapy in the year following successful kidney transplant was not associated with a reduction in risk of VTE.

Reactivation of a BCG Vaccination Scar Following the First Dose of the Moderna COVID-19 Vaccine.

The devastating effects of the COVID-19 pandemic have prompted rapid development and distribution of multiple vaccines. A 2-dose messenger RNA (mRNA) vaccine developed by Moderna (Moderna COVID-19 Vaccine) was approved in December 2020 for the prevention of COVID-19. We describe a case of BCG vaccination scar reactivation in a 48-year-old man after he received the first dose of the Moderna COVID-19 Vaccine.

Low-Dose Ketamine Infusion for Perioperative Pain Management in Patients Undergoing Laparoscopic Gastric Bypass: A Prospective Randomized Controlled Trial.

INTRODUCTION: Obesity is a common comorbidity seen in the perioperative setting and is associated with many diseases including cardiovascular disease and obstructive sleep apnea. Laparoscopic Roux-en-Y gastric bypass is the gold standard surgical treatment for patients whose weight is refractory to diet and exercise. Caring for these patients perioperatively presents unique challenges to anesthesiologists and is associated with an increased risk of adverse respiratory events. In our study, we hypothesize that a low-dose perioperative ketamine infusion will reduce opioid consumption and improve analgesia when compared to standard therapy. METHODS: This is a single-center, prospective randomized controlled study enrolling 35 patients in total. Patients were randomized equally into the ketamine and control group. Preop, intraop, and postop management regimens were standardized. The ketamine group received a 0.3 mg/kg ideal body weight ketamine bolus after induction followed by a 0.2 mg/kg/hr ketamine infusion continued into the postop setting for up to 24 hours. Data collected included total perioperative opioids used converted to oral morphine equivalents (ME), pain scores, side effects, hospital length of stay, and patient satisfaction captured via postoperative questionnaires. RESULTS: The use of perioperative opioid consumption was significantly lower in the ketamine group when compared with the control group (179.9 ME versus 248.7 ME, P=0.03). There was no statistically significant difference in pain scores or hospital length of stay postoperatively between the two groups. There were also no reported adverse respiratory events, prolonged sedation, agitation, or other side effects reported in either group. The patient satisfaction questionnaires showed a significant difference with the ketamine group reporting lower maximum pain scores, a decrease in how pain limited activities of daily living once discharged, and increased hospital pain management satisfaction scores. CONCLUSIONS: Perioperative low-dose ketamine infusions significantly reduced opioid consumption in morbidly obese patients undergoing laparoscopic gastric bypass surgery.

Cutaneous mesenchymal tumors treated with Mohs micrographic surgery: a comprehensive review.

Cutaneous mesenchymal tumors (CMT) are rare tumors with wide clinicopathologic heterogeneity. Treatment of malignant cutaneous mesenchymal tumors traditionally includes wide local excision (WLE), though Mohs micrographic surgery (MMS) has been increasingly used. A PubMed literature review of articles from inception until September 2019 related to malignant CMT and surgical treatment with MMS or WLE was completed. Dermatofibrosarcoma protuberans treated with MMS recurred in 1.2% of patients with no reported metastasis. Atypical fibroxanthoma treated with MMS recurred and metastasized in 2.7 and 2.5%, respectively. Undifferentiated pleomorphic sarcoma treated with MMS recurred in 32% with an unknown metastatic rate. Superficial leiomyosarcoma treated with MMS recurred in 3.8% with no reported metastasis. Cutaneous angiosarcoma and myofibrosarcoma treated with MMS have shown no recurrence or metastatic disease, but literature is sparse. The rarity of malignant CMT and the lack of comparative data on treatment make conclusive treatment recommendations difficult. However, recent literature suggests MMS is a useful option and potentially a superior treatment for primary cutaneous mesenchymal tumors.

Fluid Management During Kidney Transplantation: A Consensus Statement of the Committee on Transplant Anesthesia of the American Society of Anesthesiologists.

BACKGROUND: Intraoperative fluid management may affect the outcome after kidney transplantation. However, the amount and type of fluid administered, and monitoring techniques vary greatly between institutions and there are limited prospective randomized trials and meta-analyses to guide fluid management in kidney transplant recipients. METHODS: Members of the American Society of Anesthesiologists (ASA) committee on transplantation reviewed the current literature on the amount and type of fluids (albumin, starches, 0.9% saline, and balanced crystalloid solutions) administered and the different monitors used to assess fluid status, resulting in this consensus statement with recommendations based on the best available evidence. RESULTS: Review of the current literature suggests that starch solutions are associated with increased risk of renal injury in randomized trials and should be avoided in kidney donors and recipients. There is no evidence supporting the routine use of albumin solutions in kidney transplants. Balanced crystalloid solutions such as Lactated Ringer are associated with less acidosis and may lead to less hyperkalemia than 0.9% saline solutions. Central venous pressure is only weakly supported as a tool to assess fluid status. CONCLUSIONS: These recommendations may be useful to anesthesiologists making fluid management decisions during kidney transplantation and facilitate future research on this topic.

Liposomal bupivacaine interscalene nerve block in shoulder arthroplasty is not superior to plain bupivacaine: a double-blinded prospective randomized control trial.

BACKGROUND: Interscalene brachial plexus blocks are a common modality used to provide adjunctive pain relief with shoulder replacement surgery. In 2018, the Federal Drug Administration approved the use of liposomal bupivacaine (LB) for such nerve blocks. We sought to evaluate whether this formulation of bupivacaine would provide superior pain relief for shoulder replacement patients over standard bupivacaine alone. Our hypotheses were that in the LB cohort the average postoperative pain score over the first 72 hours would be significantly lower, time to block cessation would be longer, total opioid consumption would be lower, and the average patient satisfaction score regarding their pain management would be higher. MATERIALS AND METHODS: A randomized, double-blinded study was designed comparing primary shoulder replacement surgery after an interscalene block with 25 mL of 0.5% plain bupivacaine vs. 133 mg of LB with 7.5 mL of 0.5% and 7.5 mL of 0.25% plain bupivacaine. A total of 104 patients were included in the study, with an equal number in each study arm. Patients' visual analog pain scores (VAPS) were followed for their inpatient stay, first 3 full outpatient days, and at a 3-week follow-up. Use of opioid medication was recorded for the same intervals and converted to morphine milligram equivalents. The time to first opioid rescue was documented, as well as the patients' satisfaction with their pain management at both the 3-day and 3-week intervals. RESULTS: No clinically relevant advantage to the use of LB over plain bupivacaine was found. During the second postoperative day, the mean VAPS was 2.4 with LB vs. 3.3 in the standard cohort (P = .0409). The only other statistically significant finding was a higher VAPS with LB during the third full day home compared with standard bupivacaine (4.0 vs. 2.8, respectively, P = .0197). Both of these differences were less than the minimal clinically important difference of 2 for the VAPS. Analysis of the VAPS for the first and third postoperative days, the first and second full days home, and at 3 weeks revealed no significant difference. Similarly, there was no significant difference in time to first opioid rescue, total morphine milligram equivalent use, and patient satisfaction with pain management. CONCLUSION: When used for an interscalene block to provide adjunctive pain relief in shoulder replacement surgery, the addition of LB to plain bupivacaine provides no additional clinically important benefit to the patient's pain experience over standard bupivacaine.

Nontraditional Transesophageal Echocardiographic Views to Evaluate Hepatic Vasculature in Orthotopic Liver Transplantation and Liver Resection Surgery.

BACKGROUND: Utilization of intraoperative transesophageal echocardiography (TEE) during orthotopic liver transplantation (OLT) is expanding annually in high-volume transplant centers. During OLT intraoperative TEE is used to gather real-time information on cardiovascular function and intravascular volume status. Although standardized TEE views exist, there are nontraditional views described in the literature which have the potential to diagnose evolving pathology and define normal variants of hepatic vasculature. METHODS: A literature review was completed utilizing the PubMed database for English-only, peer-reviewed publications discussing nontraditional use of intraoperative TEE during OLT and hepatic vascular-related surgeries from 2009 to 2019. Both case reports and review articles were considered. RESULTS: The PubMed literature search offered 8 publications for analysis, including 7 case reports and 1 article review, revealing several nontraditional TEE views not included in a comprehensive transesophageal echocardiographic examination. These nontraditional views were generally obtained using modifications to the transgastric and bicaval views to visualize liver vasculature. We present the various techniques for obtaining these views from the 8 articles identified. CONCLUSIONS: At high-volume transplant centers, TEE use during OLT is increasing. Intraoperative TEE is a valuable tool to assess hepatic vascular structures critical to allograft/organ function without interruption of the surgical procedure. Nontraditional use of TEE to diagnose intraoperative noncardiac pathology in OLT appears underutilized and underreported. The modified hepatic and modified transgastric views we describe can be used to evaluate hepatic vasculature, influence surgical decision-making and ultimately improve patient care.

Tongue Tied after Shoulder Surgery: A Case Series and Literature Review.

This article presents three cases of cranial nerve palsy following shoulder surgery with general anesthesia in the beach chair position. All patients underwent preoperative ultrasound-guided interscalene nerve block. Two cases of postoperative hypoglossal and one case of combined hypoglossal and recurrent laryngeal nerve palsies (Tapia's syndrome) were identified. Through this case series, we provide a literature review identifying postoperative cranial nerve palsies in addition to the discussion of possible etiologies. We suggest that intraoperative patient positioning and/or airway instrumentation is most likely causative. We conclude that the beach chair position is a risk factor for postoperative hypoglossal nerve palsy and Tapia's syndrome.

Ten-year evolution of a massive transfusion protocol in a level 1 trauma centre: have outcomes improved?

BACKGROUND: We aimed to evaluate the evolution and implementation of the massive transfusion protocol (MTP) in an urban level 1 trauma centre. Most data on this topic comes from trauma centres with high exposure to life-threatening haemorrhage. This study examines the effect of the introduction of an MTP in an Australian level 1 trauma centre. METHODS: A retrospective study of prospectively collected data was performed over a 14-year period. Three groups of trauma patients, who received more than 10 units of packed red blood cells (PRBC), were compared: a pre-MTP group (2002-2006), an MTP-I group (2006-2010) and an MTP-II group (2010-2016) when the protocol was updated. Key outcomes were mortality, complications and number of blood products transfused. RESULTS: A total of 168 patients were included: 54 pre-MTP patients were compared to 47 MTP-I and 67 MTP-II patients. In the MTP-II group, fewer units of PRBC and platelets were administered within the first 24 h: 17 versus 14 (P = 0.01) and 12 versus 8 (P < 0.001), respectively. Less infections were noted in the MTP-I group: 51.9% versus 31.9% (P = 0.04). No significant differences were found regarding mortality, ventilator days, intensive care unit and total hospital lengths of stay. CONCLUSION: Introduction of an MTP-II in our level 1 civilian trauma centre significantly reduced the amount of PRBC and platelets used during damage control resuscitation. Introduction of the MTP did not directly impact survival or the incidence of complications. Nevertheless, this study reflects the complexity of real-life medical care in a level 1 civilian trauma centre.

Nontraditional Use of TEE to Evaluate Hepatic Vasculature and Guide Surgical Management in Orthotopic Liver Transplantation.

Intraoperative Transesophageal Echocardiography (TEE) during orthotopic liver transplant (OLT) is used to gather real-time information on cardiovascular function and intravascular volume status. We report a case where nonstandard TEE views were used to inspect the hepatic vasculature after allograft implantation. A 29-year-old male with secondary biliary cirrhosis with a MELD score of 20 underwent OLT using a liver from a 21-year-old brain-dead donor. Postreperfusion TEE, using the modified hepatic vein views, confirmed the presence of an inferior vena cava (IVC) suprahepatic anastomotic stenosis and hepatic vein and IVC thrombus resulting in hepatic venous outflow obstruction, allograft congestion, and hemodynamic instability. These nonstandard TEE images established the extent of suprahepatic caval outflow obstruction, in which intraoperative ultrasound was unable to definitively demonstrate. This guided real-time surgical decision-making in the postimplantation phase of the operation-ultimately leading to hepatic vein and IVC thrombectomy and revision of suprahepatic caval anastomosis.

Fatal diffuse pulmonary fat microemboli following reperfusion in liver transplantation with the use of marginal steatotic allografts.

Organ shortage is a major cause of delayed liver transplantation and increased waitlist time. The level of donor steatosis is a significant determinant in organ selection. Scarcity of organs has led some programs to expand their acceptable criteria for the percentage of steatosis. We report two cases of liver transplantation of steatotic donor organs that resulted in mortality within hours from transplantation. Postmortem analysis showed evidence of diffuse pulmonary fat microemboli likely originating from the donor organ, with marked preservation reperfusion injury. The mechanism of diffuse fat microemboli in this setting and possible relationship to other perioperative syndromes (transfusion-related lung injury, acute kidney injury, and postreperfusion syndrome) is discussed.

Evaluation of Clinical Factors Associated with Adverse Drug Events in Patients Receiving Sub-Anesthetic Ketamine Infusions.

INTRODUCTION: Sub-anesthetic ketamine is frequently used as an analgesic to reduce perioperative opioid consumption and has also been shown to have antidepressant effects. Side effects of ketamine include dizziness, diplopia, nystagmus, and psychomimetic effects. It is unclear what clinical factors may be associated with ketamine-related adverse drug events (ADEs). METHODS: We performed a retrospective review of 95 patients who received sub-anesthetic ketamine infusions at our institution. Data examined associations between ketamine-related ADEs and various clinical characteristics including chronic pain, depression, or psychiatric disorder, patient physical characteristics, chronic opioid use, perioperative opioid use, dose and duration of ketamine infusions, pain scores, and perioperative medications such as serotonergic agents, central nervous system (CNS) depressants, and analgesics. RESULTS: Overall incidence of ketamine-related ADEs was 29.5% and the incidence of psychomimetic effects was 14.8%. We observed that patients with a history of depression have a lower incidence of ketamine-related ADEs compared to patients without a history of depression (10.3% vs 37.3%; p value = 0.007). CONCLUSION: Patients with depression were found to have a statistically significant reduction in the incidence of ketamine-related ADEs. We found no statistically significant positive associations between ketamine-related ADEs and other clinical factors such as a history of chronic pain, psychiatric disease, patient physical characteristics, perioperative opioid use, dose of ketamine infusion, or co-administration of other CNS depressants.

An interpretable framework for clustering single-cell RNA-Seq datasets.

BACKGROUND: With the recent proliferation of single-cell RNA-Seq experiments, several methods have been developed for unsupervised analysis of the resulting datasets. These methods often rely on unintuitive hyperparameters and do not explicitly address the subjectivity associated with clustering. RESULTS: In this work, we present DendroSplit, an interpretable framework for analyzing single-cell RNA-Seq datasets that addresses both the clustering interpretability and clustering subjectivity issues. DendroSplit offers a novel perspective on the single-cell RNA-Seq clustering problem motivated by the definition of "cell type", allowing us to cluster using feature selection to uncover multiple levels of biologically meaningful populations in the data. We analyze several landmark single-cell datasets, demonstrating both the method's efficacy and computational efficiency. CONCLUSION: DendroSplit offers a clustering framework that is comparable to existing methods in terms of accuracy and speed but is novel in its emphasis on interpretabilty. We provide the full DendroSplit software package at https://github.com/jessemzhang/dendrosplit .