Correlation of PD-L1 Expression with Tumor Mutation Burden and Gene Signatures for Prognosis in Early-Stage Squamous Cell Lung Carcinoma

Objectives

Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.

Shear wave elastography of lumbar annulus fibrosus in adolescent idiopathic scoliosis before and after surgical intervention

To determine lumbar intervertebral disc properties with shear wave elastography in adolescent idiopathic scoliotic (AIS) patients before and after surgery, and compare them with asymptomatic controls. Twenty-five severe AIS patients with an indication for fusion surgery (15 ± 1.5 years old, the Cobb angle ranging between 40 and 93°) and fifty-nine asymptomatic adolescents (13 ± 2 years old) were included prospectively. Shear wave speed (SWS) was measured in the annulus fibrosus of L3-L4, L4-L5, and L5-S1 discs of each subject. In AIS patients, measurements took place before surgery, and 3 months (N = 13) or 1 year after (N = 12). No difference was observed between disc levels in any group. When pooling disc levels, SWS was significantly higher in preop AIS patients (4.0 ± 0.5 m/s) than in asymptomatic subjects (3.1 ± 0.5 m/s, p < 0.0001). SWS decreased 3 months postop (3.5 ± 0.3 m/s), and it decreased further towards normal values 1 year after (3.3 ± 0.4 m/s). SWS in preop AIS patients tended to decrease with the Cobb angle (Spearman’s rho = − 0.4, p = 0.05). Shear wave elastography measurements showed that discs in AIS patients were altered relative to asymptomatic ones, and this alteration tended to normalize 1 year post fusion surgery. Further studies should aim at determining if bracing of mild scoliosis has an effect on disc properties. • Shear wave elastography shows alteration of annulus fibrosus in adolescent idiopathic scoliosis. • Disc elastography tends to normalize 1 year after surgery.     

Effects of Cling Film Draping Material on Body Temperature of Mice During Surgery

General anesthesia induces many systemic effects, including thermoregulatory impairment and subsequent perioperative hypothermia. Due to the animals’ small size, monitoring and maintaining body temperatures in laboratory rodents during anesthesia is important for successful surgical outcomes and prompt anesthetic recovery. Draping materials have the potential to aid in thermal support during surgical anesthesia. In this study, rectal and surface (infrared) temperatures were measured in C57BL/6 mice under isoflurane anesthesia every 5 min for the duration of a 35-min sham surgery. In addition to placement on a circulating water bath, mice (n = 6/group) were draped with commercial cling film (CF; Press''n Seal, Glad, Oakland, CA), a conventional paper drape (PD), or no drape (ND) during surgery. Results demonstrated that CF-draped animals had significantly higher rectal temperatures than nondraped animals. Furthermore, surface temperatures of CF-draped mice were considerably higher than those of both paper-draped and undraped animals. The data indicate that cling film is an effective material to help minimize hypothermia in mice and potentially in other laboratory rodents requiring general anesthesia.

Surgery and anesthesia introduce many challenges, especially in veterinary medicine, due to the diversity of species. One major challenge during general anesthesia involves changes in an animal''s thermoregulatory ability.^1,14 Body temperatures in mice and rats fall significantly during anesthesia if no thermal support is provided.^29,30 Hypothermia occurs due to drug-induced alterations to the thermoregulatory center, inadequate circulation, and a loss of body heat to the environment from evaporation, radiation, conduction, and convection.⁷ Mice are particularly susceptible to hypothermia, due to their large surface area per gram of body weight, which permits significant physiologic changes in response to fluctuations in the ambient temperature.³¹ Covering the animal''s body with towels, drapes, or blankets to reduce the area exposed to the environment can minimize heat loss.^6,7,13 Placing the animal on an insulated surface can limit conductive heat loss. In larger animals, warmed fluids can be given perioperatively, heated anesthetic gasses can be administered, and heated blankets and heat packs can be applied to body surfaces to provide exogenous heat.^1,7 Safer and more practical methods for rodents are circulating water heating blankets, thermal gel packs, and warming lamps, which are commonly used for thermal support during anesthesia.^5,14 Addressing all of these factors can contribute to maintaining normothermia during anesthesia.Risk of mortality is elevated during anesthesia and in the postoperative period, including in rodents.^1,13 Hypothermia induced by anesthesia can negatively affect rodents by altering vital parameters such as heart rate and blood pressure and delaying anesthetic recovery.^3,5,12,19 These risks require careful selection of an appropriate anesthetic protocol and careful monitoring of the patient throughout anesthesia until full recovery occurs. Strict anesthetic monitoring and the use of supplemental heat devices have been shown to reduce the likelihood of complications, improve overall postoperative recovery, and reduce mortality associated with surgical procedures.^1,7,15,16 However, due to these species’ small size, monitoring equipment must be specialized and is often costly. Cost-effective and practical alternative equipment and materials would facilitate monitoring and care of rodents.Various draping options are available for rodent surgery, and their use is vital for both sterile technique and heat retention. Traditionally, paper draping material has been a popular option, because it is relatively inexpensive and can be autoclaved together with surgical instruments.^15,16 Some institutions have adopted varying methods and types of draping, including no drape and paper draping. Commercial cling film (CF) has been used as draping due to its low cost, ease of use, and sterility straight out of the box.⁹ Our study team sought to evaluate the effects of draping material on intraoperative thermoregulation in mice by measuring rectal temperature (modified rectal probe) and surface temperature (infrared device) during a 35-min laparotomy procedure, with both temperature devices chosen for affordability and availability. We hypothesized that mice draped with CF would maintain a higher intraoperative body temperature under general anesthesia than would mice with traditional paper drapes or no drape.     

Anti-Inflammatory Activity in the Low Molecular Weight Fraction of Commercial Human Serum Albumin (LMWF5A)

The innate immune system is increasingly being recognized as a critical component in osteoarthritis (OA) pathophysiology. An ex vivo immunoassay utilizing human peripheral blood mononuclear cells (PBMC) was developed in order to assess the OA anti-inflammatory properties of the low molecular weight fraction (<5 kDa) of commercial human serum albumin (LMWF5A). PBMC from various donors were pre-incubated with LMWF5A before LPS stimulation. TNFα release was measured by ELISA in supernatants after an overnight incubation. A ≥ 30% decrease in TNFα release was observed. This anti-inflammatory effect is potentially useful in assessing potency of LMWF5A for the treatment of OA.