Analgesic efficacy of paraspinal interfascial plane blocks performed with the use of neurophysiology monitoring for posterior cervical laminectomy surgery: a case series.

Posterior cervical spine surgery often requires large posterior midline incision which can result in poorly controlled postoperative pain, arises from iatrogenic mechanical damage, intraoperative retraction and resection to structures such as bone, ligaments, muscles, intervertebral disks, and zygapophysial joints. Local anesthetics may be utilized for infiltration of the surgical wound; however, their analgesic efficacy has not been studied in this surgical approach. Here we report a case series. Given the potential for targeted sensory dorsal ramus nerve blocks to provide better and extended analgesia, we explored the feasibility of using cervical paraspinal interfascial plane (PIP) blocks in conjunction with neurophysiologic monitoring for postoperative analgesia after posterior cervical laminectomy. Our experience with the cervical paraspinal interfascial plane blocks has revealed that they can be used safely without affecting neurophysiologic monitoring and result in better pain control and reduced opiate use in the postoperative period. Cervical PIP blocks may be useful in controlling pain for posterior cervical laminectomy surgery without compromising neurophysiologic monitoring.

Thoracolumbar Dorsal Ramus Nerve Block Using Continuous Multiorifice Infusion Catheters: A Novel Technique for Postoperative Analgesia After Scoliosis Surgery.

BACKGROUND: This is a brief technical report about a novel regional anesthesia technique in which local anesthetic was deposited around the thoracolumbar dorsal rami nerves via 4 multiorifice pain catheters to obtain analgesia for posterior spinal fusion surgery on scoliosis patients. Scoliosis is the most common deformity of the spine. Currently, most surgeons prefer a dual rod, segmental spinal fixation system that allows multiple anchor points for attachment to the deformed spine. Scoliosis surgery is an extremely painful surgical procedure due to the large incision, surgical trauma to superficial and deep muscles of the back, and the insertion of pedicle screws and metal rods directly into the vertebral column. Postoperative pain management remains very challenging. METHODS: Three patients presented with scoliosis. Intraoperatively, 4 multiorifice catheters were placed lateral to the implanted pedicle screws. Two catheters were placed on each side, and a continuous infusion of 0.2 % ropivacaine was initiated postoperatively to improve the patient's pain control. The catheters remained in place for 48 hours postoperatively and were removed by the surgical team. Gentle traction was applied similar to the way epidural catheters are removed. RESULTS: All 3 patients reported very low pain scores, low doses of opioid consumption, and satisfaction with their pain control throughout their hospitalization. CONCLUSIONS: Our study results suggest that a thoracolumbar dorsal ramus nerve block using continuous multiorifice infusion catheters significantly improved postoperative comfort and pain and that its implementation into a multimodal analgesic regimen is relatively easy to achieve.

Rapid clearance of heavy chain-modified hyaluronan during resolving acute lung injury.

BACKGROUND: Several inflammatory lung diseases display abundant presence of hyaluronic acid (HA) bound to heavy chains (HC) of serum protein inter-alpha-inhibitor (IαI) in the extracellular matrix. The HC-HA modification is critical to neutrophil sequestration in liver sinusoids and to survival during experimental lipopolysaccharide (LPS)-induced sepsis. Therefore, the covalent HC-HA binding, which is exclusively mediated by tumor necrosis factor α (TNFα)-stimulated-gene-6 (TSG-6), may play an important role in the onset or the resolution of lung inflammation in acute lung injury (ALI) induced by respiratory infection. METHODS: Reversible ALI was induced by a single intratracheal instillation of LPS or Pseudomonas aeruginosa in mice and outcomes were studied for up to six days. We measured in the lung or the bronchoalveolar fluid HC-HA formation, HA immunostaining localization and roughness, HA fragment abundance, and markers of lung inflammation and lung injury. We also assessed TSG-6 secretion by TNFα- or LPS-stimulated human alveolar macrophages, lung fibroblast Wi38, and bronchial epithelial BEAS-2B cells. RESULTS: Extensive HC-modification of lung HA, localized predominantly in the peri-broncho-vascular extracellular matrix, was notable early during the onset of inflammation and was markedly decreased during its resolution. Whereas human alveolar macrophages secreted functional TSG-6 following both TNFα and LPS stimulation, fibroblasts and bronchial epithelial cells responded to only TNFα. Compared to wild type, TSG-6-KO mice, which lacked HC-modified HA, exhibited modest increases in inflammatory cells in the lung, but no significant differences in markers of lung inflammation or injury, including histopathological lung injury scores. CONCLUSIONS: Respiratory infection induces rapid HC modification of HA followed by fragmentation and clearance, with kinetics that parallel the onset and resolution phase of ALI, respectively. Alveolar macrophages may be an important source of pulmonary TSG-6 required for HA remodeling. The formation of HC-modified HA had a minor role in the onset, severity, or resolution of experimental reversible ALI induced by respiratory infection with gram-negative bacteria.

TGFß1 mediates alcohol-induced Nrf2 suppression in lung fibroblasts.

BACKGROUND: Chronic alcohol ingestion induces the expression of transforming growth factor beta-1(TGFß1), inhibits nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated activation of the antioxidant response element (ARE), depletes alveolar glutathione pools, and potentiates acute lung injury. In this study, we examined the mechanistic relationship between TGFß1 and Nrf2-ARE signaling in the experimental alcoholic lung. METHODS: Wild-type mice were treated ± alcohol in drinking water for 8 weeks and their lungs were assessed for Nrf2 expression. In parallel, mouse lung fibroblasts were cultured ± alcohol and treated ± sulforaphane (SFP; an activator of Nrf2), ±TGFß1, ±TGFß1 neutralizing antibody, and/or ±activin receptor-like kinase 5 inhibitors (to block TGß1 receptor signaling) and then analyzed for the expression of Nrf2, Kelch-like ECH-associated protein 1 (Keap1) and TGFß1, Nrf2-ARE activity, and the expression of the Nrf2-ARE-dependent antioxidants glutathione s-transferase theta 2 (GSTT2) and glutamate-cysteine ligase catalytic subunit (GCLC). Finally, silencing RNA (siRNA) of Nrf2 was then performed prior to alcohol exposure and subsequent analysis of TGFß1 expression. RESULTS: Alcohol treatment in vivo or in vitro decreased Nrf2 expression in murine whole lung and lung fibroblasts, respectively. In parallel, alcohol exposure in vitro decreased Keap1 gene and protein expression in lung fibroblasts. Furthermore, alcohol exposure increased TGFß1 expression but decreased Nrf2-ARE activity and expression of the ARE-dependent genes for GSTT2 and GCLC. These effects of alcohol were prevented by treatment with SFP; in contrast, Nrf2 SiRNA expression exacerbated alcohol-induced TGFß1 expression. Finally, TGFß1 treatment directly suppressed Nrf2-ARE activity whereas blocking TGFß1 signaling attenuated alcohol-induced suppression of Nrf2-ARE activity. CONCLUSIONS: Alcohol-induced oxidative stress is mediated by TGFß1, which suppresses Nrf2-ARE-dependent expression of antioxidant defenses and creates a vicious cycle that feeds back to further increase TGFß1 expression. These effects of alcohol can be mitigated by activation of Nrf2, suggesting a potential therapy in individuals at risk for lung injury due to alcohol abuse.

Efficient assessment of peripheral blood lymphocytosis in adults: developing new thresholds for blood smear review by pathologists.

BACKGROUND: Peripheral smear review is a critical, but labor intensive adjunct for evaluation of lymphocytosis. Standard practice based on consensus guidelines is to review cases with absolute lymphocyte count (ALC) >5×109/L. We hypothesize that identifying cases for review by applying appropriately adjusted ALC and age discriminators will decrease laboratory workload without compromising patient care. METHODS: 1170 complete blood counts with ALCs >5×109/L analyzed in the core laboratory during a 2-year period were included. Patients were categorized into diagnostic groups based on follow-up criteria. A total of 402 patients with new onset lymphocytosis who met criteria for reactive lymphocytosis (82%) or lymphoproliferative disorder (18%) were used to establish optimal ALC and age thresholds from receiver operating characteristic (ROC) curve analysis. RESULTS: ALC as a discriminator for neoplastic lymphocytosis had an ROC area under the curve (AUC) of 0.732. Selecting cases with ALC >10×109/L enriched the proportion of neoplastic cases in the review pool (90% specificity); however, many cases with ALC below this threshold were also neoplastic (52% sensitivity). For cases with ALC between 5 and 10×109/L, age as a discriminator had an ROC AUC of 0.886. Selecting patients >50 years old in this group for review captured the neoplastic cases while excluding the reactive cases (93% sensitivity, 62% specificity). When applied to a validation cohort, the predictive performance of the thresholds was maintained while reducing smears reviewed by 50%. CONCLUSIONS: We show that modifying the standard 5×109/L ALC smear review threshold through retrospective analysis of institutional data can reduce laboratory workload without compromising quality.

The Legionella IcmSW complex directly interacts with DotL to mediate translocation of adaptor-dependent substrates.

Legionella pneumophila is a Gram-negative bacterium that replicates within human alveolar macrophages by evasion of the host endocytic pathway through the formation of a replicative vacuole. Generation of this vacuole is dependent upon the secretion of over 275 effector proteins into the host cell via the Dot/Icm type IVB secretion system (T4SS). The type IV coupling protein (T4CP) subcomplex, consisting of DotL, DotM, DotN, IcmS and IcmW, was recently defined. DotL is proposed to be the T4CP of the L. pneumophila T4SS based on its homology to known T4CPs, which function as inner-membrane receptors for substrates. As a result, DotL is hypothesized to play an integral role(s) in the L. pneumophila T4SS for the engagement and translocation of substrates. To elucidate this role, a genetic approach was taken to screen for dotL mutants that were unable to survive inside host cells. One mutant, dotLY725Stop, did not interact with the type IV adaptor proteins IcmS/IcmW (IcmSW) leading to the identification of an IcmSW-binding domain on DotL. Interestingly, the dotLY725Stop mutant was competent for export of one class of secreted effectors, the IcmSW-independent substrates, but exhibited a specific defect in secretion of IcmSW-dependent substrates. This differential secretion illustrates that DotL requires a direct interaction with the type IV adaptor proteins for the secretion of a major class of substrates. Thus, by identifying a new target for IcmSW, we have discovered that the type IV adaptors perform an additional role in the export of substrates by the L. pneumophila Dot/Icm T4SS.