Case Series of Multicontact Peripheral Nerve Stimulation in the Transversus Abdominis Plane for Chronic Abdominal Wall Pain.

OBJECTIVES: Managing abdominal pain can be difficult. This is due to the nonspecific nature of the pain, the multiple etiologies, and the different mechanisms underlying this type of pain. Abdominal wall pain in particular poses its own challenges. Traditionally, chronic abdominal wall pain has been managed with nonopioid analgesics, and in severe cases, opioid therapy has been considered. For patients with chronic abdominal wall pain refractory to medication management, peripheral nerve blocks and spinal cord stimulation also have been trialed with some success. In this study, we present a case series in patients with chronic abdominal wall pain who were treated with a multicontact peripheral nerve stimulation (PNS) system in the transversus abdominis plane (TAP). MATERIALS AND METHODS: This was a single-center, retrospective case series. Data were included from adults with chronic abdominal wall pain whose symptoms were refractory to standard medical management and who underwent a multicontact PNS system placement in the TAP. RESULTS: Four patients met the inclusion criteria. All four patients underwent a multicontact PNS trial lead placement in the TAP. One patient reported no benefit from the trial. The remaining three patients underwent a permanent multicontact PNS system placement in the TAP. CONCLUSIONS: In patients with chronic abdominal wall pain whose symptoms are refractory to conservative medical management, PNS may be an alternative treatment option. As the use of PNS for chronic abdominal wall pain and other fascial planes continues to develop, additional research is necessary to determine optimal placements and specific stimulation parameters.

Carotid approach to anterior circulation thromboembolectomy in an adult with failing fontan physiology: a case report.

BACKGROUND: Anesthetic management of an adult with failing Fontan physiology is complicated given inherent anatomical and physiological alterations. Neurosurgical interventions including thromboembolectomy may be particularly challenging given importance of blood pressure control and cerebral perfusion. CASE PRESENTATION: We describe a 29 year old patient born with double outlet right ventricle (DORV) with mitral valve atresia who after multi-staged surgeries earlier in life, presented with failing Fontan physiology. She was admitted to the hospital almost 29 years after her initial surgeries to undergo workup for a dual heart and liver transplant in the context of a failing Fontan with elevated end diastolic pressures, NYHA III heart failure symptoms, and liver cirrhosis from congestive hepatopathy. During the workup in the context of holding anticoagulation for invasive procedures, she developed a middle cerebral artery (MCA) stroke requiring a thromboembolectomy via left carotid artery approach. DISCUSSION AND CONCLUSIONS: This case posed many challenges to the anesthesiologist including airway control, hemodynamic and cardiopulmonary monitoring, evaluation of perfusion, vascular access, and management of anticoagulation in an adult patient in heart and liver failure with Fontan physiology undergoing thromboembolectomy for MCA embolic stroke.

Local infusion of ropivacaine for pain control after osseous free flaps: Randomized controlled trial.

BACKGROUND: Donor site pain after osteocutaneous free flap surgery contributes to postoperative morbidity and impairs recovery. We evaluated the efficacy of local infusion of ropivacaine for treating donor-site pain after surgery. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of patients undergoing osteocutaneous fibula or scapular tip free flaps for head and neck reconstruction at Mount Sinai Hospital. Patients were randomized to receive local infusion of ropivacaine or saline. We compared Visual Analog Scale pain scores for donor-site specific pain 48 hours after surgery. RESULTS: There were 8 fibular free flap and 10 scapular free flap reconstructions. Average donor-site pain scores were 29 ± 22 and 31 ± 28 mm (P = .88) for placebo and ropivacaine arms, respectively. The trial was stopped after the planned interim analysis for futility of the intervention. CONCLUSIONS: Local infusion of ropivacaine did not affect donor-site specific pain scores in this population. ClinicalTrials.gov Identifier: NCT03349034.

Effects of anesthetic interventions on breast cancer behavior, cancer-related patient outcomes, and postoperative recovery.

This narrative review will summarize our current understanding of the effects of perioperative interventions on patients undergoing surgical removal of breast malignancies. It will focus on how different anesthetic agents and perioperative interventions might affect both breast cancer behavior and/or tumor recurrence as well as postoperative recovery. The main objective of this study will be to describe the evidence and critically analyze preclinical and clinical studies on the use of intravenous versus inhaled anesthetic agents, opioids, regional anesthetics, and anesthetic adjuncts in patients undergoing breast cancer resection. We will look both at the evidence regarding cancer-related outcomes and postoperative recovery. A search of PubMed, from inception to May 2017 was performed using Mesh terms Breast Neoplasms [Mesh] OR cancer AND breast AND Anesthesia [Mesh]; "Anesthetics"[Mesh] AND "Breast Neoplasms/surgery"[Mesh]. Although no optimal anesthetic combination has been identified for patients undergoing breast cancer resection, it should be noted that based on the available evidence, an ideal anesthetic in this patient population would involve a combination of TIVA (propofol), regional anesthesia (paravertebral block)), non opioid sedatives (clonidine or dexmedetomidine), and COX-2 inhibition (ketorolac). Based on the current evidence, this combination of anesthetic and analgesic agents has the best chance of improving cancer-related outcomes and postoperative recovery.

Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity.

Human high-affinity antibodies to pathogens often recognize unrelated ligands. The molecular origin and the role of this polyreactivity are largely unknown. Here, we report that HIV-1 broadly neutralizing antibodies (bNAbs) are frequently polyreactive, cross-reacting with non-HIV-1 molecules, including self-antigens. Mutating bNAb genes to increase HIV-1 binding and neutralization also results in de novo polyreactivity. Unliganded paratopes of polyreactive bNAbs with improved HIV-1 neutralization exhibit a conformational flexibility, which contributes to enhanced affinity of bNAbs to various HIV-1 envelope glycoproteins and non-HIV antigens. Binding adaptation of polyreactive bNAbs to the divergent ligands mainly involves hydrophophic interactions. Plasticity of bNAbs' paratopes may, therefore, facilitate accommodating divergent viral variants, but it simultaneously triggers promiscuous binding to non-HIV-1 antigens. Thus, a certain level of polyreactivity can be a mark of adaptable antibodies displaying optimal pathogens' recognition.

Medical student preparedness for an era of personalized medicine: findings from one US medical school.

AIM: The objective of this research was to assess medical student preparedness for the use of personalized medicine. MATERIALS & METHODS: A survey instrument measuring attitude toward personalized medicine, perceived knowledge of genomic testing concepts and perceived ability to apply genomics to clinical care was distributed to students in medical school (MS) years 1-4. RESULTS: Of 212 participants, 79% felt that it was important to learn about personalized medicine, but only 6% thought that their medical education had adequately prepared them to practice personalized medicine. Attitude did not vary across years; knowledge and ability increased after MS1, but not after MS2. CONCLUSION: While medical students support the use of personalized medicine, they do not feel prepared to apply genomics to clinical care.

Getting to Know Patients.

As a third-year medical student, I have the job of being the first person from the medical team to check in on patients in the morning, follow up on consults that they may need, and communicate with people from other services who are involved with patients' care. Because third-year medical students have the most time of anyone on the medical team, we are encouraged to get to know our patients. We are encouraged to take time to understand our patients' conditions on both a medical and personal level, that is, both to read about their complex diseases and to talk about their preferences, goals, families, and lives outside the hospital. As best we can, we then communicate their personal needs and preferences to the medical team of doctors, nurses, social workers and others. What could be wrong with that?

Integrative network modeling approaches to personalized cancer medicine.

The ability to collect millions of molecular measurements from patients is a now a reality for clinical medicine. This reality has created the challenge of how to integrate these vast amounts of data into models that accurately predict complex pathophysiology and can translate this complexity into clinically actionable outputs. Integrative informatics and data-driven approaches provide a framework for analyzing large-scale datasets and combining them into multiscale models that can be used to determine the key drivers of disease and identify optimal therapies for treating tumors. In this perspective we discuss how an integrative modeling approach is being used to inform individual treatment decisions, highlighting a recent case report that illustrates the challenges and opportunities for personalized oncology.

Broadly neutralizing antibodies that inhibit HIV-1 cell to cell transmission.

The neutralizing activity of anti-HIV-1 antibodies is typically measured in assays where cell-free virions enter reporter cell lines. However, HIV-1 cell to cell transmission is a major mechanism of viral spread, and the effect of the recently described broadly neutralizing antibodies (bNAbs) on this mode of transmission remains unknown. Here we identify a subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4(+) lymphocytes. These antibodies target either the CD4-binding site (NIH45-46 and 3BNC60) or the glycan/V3 loop (10-1074 and PGT121) on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. These antibodies accumulate at virological synapses and impair the clustering and fusion of infected and target cells and the transfer of viral material to uninfected T cells. In addition, they block viral cell to cell transmission to plasmacytoid DCs and thereby interfere with type-I IFN production. Thus, only a subset of bNAbs can efficiently prevent HIV-1 cell to cell transmission, and this property should be considered an important characteristic defining antibody potency for therapeutic or prophylactic antiviral strategies.

Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies.

Broadly neutralizing HIV antibodies (bNAbs) can recognize carbohydrate-dependent epitopes on gp120. In contrast to previously characterized glycan-dependent bNAbs that recognize high-mannose N-glycans, PGT121 binds complex-type N-glycans in glycan microarrays. We isolated the B-cell clone encoding PGT121, which segregates into PGT121-like and 10-1074-like groups distinguished by sequence, binding affinity, carbohydrate recognition, and neutralizing activity. Group 10-1074 exhibits remarkable potency and breadth but no detectable binding to protein-free glycans. Crystal structures of unliganded PGT121, 10-1074, and their likely germ-line precursor reveal that differential carbohydrate recognition maps to a cleft between complementarity determining region (CDR)H2 and CDRH3. This cleft was occupied by a complex-type N-glycan in a "liganded" PGT121 structure. Swapping glycan contact residues between PGT121 and 10-1074 confirmed their importance for neutralization. Although PGT121 binds complex-type N-glycans, PGT121 recognized high-mannose-only HIV envelopes in isolation and on virions. As HIV envelopes exhibit varying proportions of high-mannose- and complex-type N-glycans, these results suggest promiscuous carbohydrate interactions, an advantageous adaptation ensuring neutralization of all viruses within a given strain.