German Corrales

Bio: German Corrales is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Medicine & Perioperative. The author has an hindex of 2, co-authored 9 publications receiving 9 citations.

Chemotherapy-induced peripheral neuropathy in a dish: dorsal root ganglion cells treated in vitro with paclitaxel show biochemical and physiological responses parallel to that seen in vivo.

Abstract: The mechanisms underlying chemotherapy-induced peripheral neuropathy have yet to be fully elucidated, but primary afferent neurons have emerged as an especially vulnerable initiating pathophysiological target. An important recent study has also shown that the initial toxicity produced by paclitaxel in patients was highly predictive of long-term outcome. In this study, we therefore focused on defining the mechanisms of acute toxicity produced by paclitaxel treatment on primary sensory neurons under in vitro conditions. In primary rat dorsal root ganglion (DRG) culture with paclitaxel, an increase of pERK and pp38 was observed at 2 hours, and this was accompanied by an increase in expression and release of C-C chemokine ligand 2 (CCL2). There was no change in pJNK. The increase in pERK was sustained at 48 hours of exposure when the expression of TLR4, MyD88, and IL-6 was also increased. IL-6 and CCL2 were colocalized to TLR4-positive cells, and all these responses were prevented by coincubation with a TLR4 antagonist (LPS-RS). Whole-cell patch-clamp recordings revealed that DRG neurons developed spontaneous depolarizing fluctuations (DSFs) in membrane potential and hyperexcitability to current injection but no ectopic action potential activity at 24 and 48 hours of paclitaxel incubation. However, CCL2 applied to cultured neurons not only induced DSFs but also evoked action potentials. Evidence of oxidative stress and mitotoxicity was observed at 48 hours of exposure. These results closely parallel the responses measured in the DRG with paclitaxel exposure in vivo and so indicate that acute toxicity of paclitaxel on the DRG can be modelled using an in vitro approach.

The Impact of Thoracic Epidural Analgesia Versus Four Quadrant Transversus Abdominis Plane Block on Quality of Recovery After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Surgery: A Single-Center, Noninferiority, Randomized, Controlled Trial

Abstract: Recovery after CRS-HIPEC influenced by several factors, including pain and opioid consumption. We hypothesized that 4Q-TAP blocks provide not inferior quality of recovery compared with TEA after CRS-HIPEC. We conducted a randomized, controlled trial to determine whether 4-quadrant transversus abdominis plane (4Q-TAP) block analgesia was noninferior to thoracic epidural (TEA) among patients who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS HIPEC). Patients 18 years or older who underwent a CRS-HIPEC surgery were randomly assigned to have either TEA or 4Q-TAP blocks. The primary outcome of this study was the change in quality of recovery 2 days after surgery. Secondary outcomes included quality of recovery on Days 1, 3, 5, 7, 10, and 30 postoperatively, opioid consumption, pain intensity, length of stay, and postoperative complications. Analyses were performed on a per-protocol basis. Sixty-eight patients were included in the analysis. The difference between 4Q-TAP and TEA in the mean QoR-15 change from surgery at postoperative Days 1, 2, and 3 was 0.80 (P = 0.004), −4.5 (P = 0.134), and 3.4 (P = 0.003), respectively. All differences through postoperative day 30 were significantly within the noninferiority boundary of −10 except at postoperative Day 2 (P = 0.134). Length of stay, opioid-related adverse events, and frequency and grade of complications were not significantly different between TEA and 4Q-TAP patients. Despite the significantly higher use of opioids after CRS-HIPEC in patients with 4Q-TAP blocks, their short-term quality of recovery was not inferior to those treated with TEA. Patients undergoing CRS-HIPEC can be effectively managed with 4Q-TAP blocks.

Low doses of methylnaltrexone inhibits head and neck squamous cell carcinoma growth in vitro and in vivo by acting on the mu-opioid receptor.

Abstract: The Mu-opioid receptor (MOR) has been implicated in tumorigenesis and metastasis. Methylnaltrexone (MNTX), an antagonist of MOR, has shown to inhibit tumor growth and metastasis in lung cancer cell lines. The effect of MNTX on other cell lines such as head and neck squamous cell carcinoma (HNSCC) has not been investigated. We measured the expression and activity of the receptor in different HNSCC cell lines. Then, we evaluated the impact of modulating the expression MOR and the effect of MNTX on the proliferation, clonogenic activity, invasion, and migration of two HNSCC (FaDu and MDA686Tu) cell lines expressing MOR and one cell line (UMSCC47) not expressing the receptor. We also evaluated the impact of MNTX on tumor growth and metastasis formation in vivo. Activation of the receptor with [d-Ala2,N-Me-Phe4, Gly5-ol] (DAMGO) caused a significant reduction in cyclic adenosine monophosphate levels in FaDu cells. Knockdown of MOR inhibited in vitro aggressive cell behaviors on FaDu and MDA686Tu cells and correlated with a reduction in markers of epithelial-mesenchymal transition. In vitro studies showed that MNTX strongly inhibited the proliferation, clonogenic activity, invasion, and migration of FaDu and MDA686Tu cells but has no effect on UMSCC47 cells. In vivo experiments demonstrated that MNTX suppresses tumor growth in HNSCC cell tumor-bearing mice. Our studies indicate that MOR could be considered as a therapeutic target to treat HNSCC.

Opioid free anesthesia: feasible?

Abstract: Purpose of review The present review aims to address the feasibility of opioid free anesthesia (OFA). The use of opioids to provide adequate perioperative pain management has been a central practice of anesthesia, and only recently has been challenged. Understanding the goals and challenges of OFA is essential as the approach to intraoperative analgesia and postsurgical management of pain has shifted in response to the opioid epidemic in the United States. Recent findings OFA is an opioid sparing technique, which focuses on multimodal or balanced analgesia, relying on nonopioid adjuncts and regional anesthesia. Enhanced recovery after surgery protocols, often under the auspices of a perioperative pain service, can help guide and promote opioid reduced and OFA, without negatively impacting perioperative pain management or recovery. Summary The feasibility of OFA is evident. However, there are limitations of this approach that warrant discussion including the potential for adverse drug interactions with multimodal analgesics, the need for providers trained in regional anesthesia, and the management of pain expectations. Additionally, minimizing opioid use perioperatively also requires a change in current prescribing practices. Monitors that can reliably quantify nociception would be helpful in the titration of these analgesics and enable anesthesiologists to achieve the goal in providing personalized perioperative medicine.

Normalization of cholesterol metabolism in spinal microglia alleviates neuropathic pain.

Abstract: Neuroinflammation is a major component in the transition to and perpetuation of neuropathic pain states. Spinal neuroinflammation involves activation of TLR4, localized to enlarged, cholesterol-enriched lipid rafts, designated here as inflammarafts. Conditional deletion of cholesterol transporters ABCA1 and ABCG1 in microglia, leading to inflammaraft formation, induced tactile allodynia in naive mice. The apoA-I binding protein (AIBP) facilitated cholesterol depletion from inflammarafts and reversed neuropathic pain in a model of chemotherapy-induced peripheral neuropathy (CIPN) in wild-type mice, but AIBP failed to reverse allodynia in mice with ABCA1/ABCG1-deficient microglia, suggesting a cholesterol-dependent mechanism. An AIBP mutant lacking the TLR4-binding domain did not bind microglia or reverse CIPN allodynia. The long-lasting therapeutic effect of a single AIBP dose in CIPN was associated with anti-inflammatory and cholesterol metabolism reprogramming and reduced accumulation of lipid droplets in microglia. These results suggest a cholesterol-driven mechanism of regulation of neuropathic pain by controlling the TLR4 inflammarafts and gene expression program in microglia and blocking the perpetuation of neuroinflammation.

Paclitaxel in vitro reversibly sensitizes the excitability of IB4(−) and IB4(+) sensory neurons from male and female rats

Abstract: Paclitaxel produces a chemotherapy‐induced peripheral neuropathy that persists in 50–60% of cancer patients upon treatment. Evidence from animal models suggests an axonopathy of peripheral A‐ and C‐type fibres that affects their excitability. However, direct effects of paclitaxel on sensory neuron excitability and sexual dimorphism remain poorly understood.

Impact of Ultrasound-Guided Deep Serratus Anterior Plane Block Combined With Dexmedetomidine as an Adjuvant to Ropivacaine Inpatient Quality of Recovery Scores Undergoing Modified Radical Mastectomy: A Randomized Controlled Trial

Abstract: Background Breast cancer has overtaken lung cancer as the most commonly diagnosed malignancy and is the leading cause of cancer-related death in women. Surgery is the only possible cure for breast cancer, and the incidence of acute postoperative pain (APP) is high in breast surgery. Previous reports suggested that ultrasound-guided deep serratus anterior plane block (dSAPB) provided effective blockade to relieve pain after modified radical mastectomy for breast cancer. In fact, despite the long-acting local anesthetic agents used, the patient’s pain cannot completely be eliminated due to the short duration of anesthesia. Dexmedetomidine as an adjunct to local anesthetics can prolong peripheral nerve block duration. However, no study has investigated the role of dSAPB with dexmedetomidine in the quality of recovery scores undergoing modified radical mastectomy. Thus, this study was conducted aiming at this aspect. Material and Methods This single-center, double-blind, randomized clinical trial was conducted at Bethune International Peace Hospital. A total of 88 participants of elective modified radical mastectomy were enrolled from May and November 2021. Ultrasound-guided dSAPB combined with 30 ml of 0.375% ropivacaine or 30 ml of 0.375% ropivacaine with dexmedetomidine (1 μg/kg) was administrated before anesthesia at the fourth to fifth ribs of the axillary midline. The primary outcome was quality of recovery, measured 24 h postoperatively using the QoR-15. Secondary outcomes were the Visual Analogue Scale (VAS) scores at rest and movement at 1, 6, 12, 24, and 48 h after surgery, 48 h sufentanil consumption postoperatively, the incidence of postoperative nausea and vomiting (PONV), length of post-anesthesia care unit (PACU) stay, dizziness, delirium, SAPB-related adverse events, and patient’s satisfaction with pain management. Results Among the 88 participants, 8 did not meet the inclusion criteria; the other 80 were randomized to receive dSAPB combined with ropivacaine (Group R, N=40) and dSAPB combined with ropivacaine plus DEX (Group RD, N=40), of which a total of 7 (4 in Group R and 3 in Group RD) were excluded due to protocol deviation. Eventually,73 participants (36 in Group R and 37 in Group RD) were included for final analysis, with age (SD, years, 54.08[6.28] vs. 54.62[7.44], p=0.740), body mass index (BMI) (SD, 27.96[1.67] vs. 27.57[2.38], p=0.428), and median preoperative global QoR-15 score (interquartile range (IQR), 127[123.25–131] vs. 126[121–130], p=0.662). The median postoperative global QoR-15 score (IQR, 107[103–112] vs. 109.5[107–114], p=0.016), VAS score at rest at 12th hour (IQR, 1[1–2] vs. 1[1–2], p=0.033), VAS score in movement at 12th hour (IQR, 2[1–3] vs. 2[1–3], p=0.014) and at 24th hour (IQR, 3[2–3] vs. 3[2–3], p=0.040), and median sufentanil rescues consumption (IQR, 14[12–17 vs. 14[12–15], p=0.022] of Group RD were significantly lower than those of the Group R. Patient satisfaction score (SD, 8.28[0.70] vs. 8.62[0.59], p=0.024) of Group RD were significantly higher than those of the Group R. Conclusion The ultrasound-guided dSAPB combined with dexmedetomidine plus ropivacaine may improve the QoR-15 in patients undergoing modified radical mastectomy and indicates that it may be a useful intervention to aid recovery following breast cancer surgery. Furthermore, participants in the ropivacaine with DEX group met the superior pain relief in the early postoperative period, reduced postoperative cumulative opioid consumption, increased patient satisfaction, and no increase in the incidence of complications.