Actinomycosis Confined to the Nasal Septum.

Actinomycosis is common in the head and neck region but rarely occurs in the nasal septum. A 75-year-old male patient with an edentulous maxilla, hypertension, and diabetes developed actinomycosis confined to the nasal septum and showed mucosal necrosis and septal bony sequestration. The patient underwent surgery and medication therapy; this case was reported using endoscopic photographs and radiographs and a literature review was conducted to provide further context and understanding of the condition of the patient.

PRMT5 inhibition drives therapeutic vulnerability to combination treatment with BCL-2 inhibition in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an incurable B-cell malignancy that comprises up to 6% of non-Hodgkin lymphomas diagnosed annually and is associated with a poor prognosis. The average overall survival of patients with MCL is 5 years, and for most patients who progress on targeted agents, survival remains at a dismal 3 to 8 months. There is a major unmet need to identify new therapeutic approaches that are well tolerated to improve treatment outcomes and quality of life. The protein arginine methyltransferase 5 (PRMT5) enzyme is overexpressed in MCL and promotes growth and survival. Inhibition of PRMT5 drives antitumor activity in MCL cell lines and preclinical murine models. PRMT5 inhibition reduced the activity of prosurvival AKT signaling, which led to the nuclear translocation of FOXO1 and modulation of its transcriptional activity. Chromatin immunoprecipitation and sequencing identified multiple proapoptotic BCL-2 family members as FOXO1-bound genomic loci. We identified BAX as a direct transcriptional target of FOXO1 and demonstrated its critical role in the synergy observed between the selective PRMT5 inhibitor, PRT382, and the BCL-2 inhibitor, venetoclax. Single-agent and combination treatments were performed in 9 MCL lines. Loewe synergy scores showed significant levels of synergy in most MCL lines tested. Preclinical, in vivo evaluation of this strategy in multiple MCL models showed therapeutic synergy with combination venetoclax/PRT382 treatment with an increased survival advantage in 2 patient-derived xenograft models (P ≤ .0001, P ≤ .0001). Our results provide mechanistic rationale for the combination of PRMT5 inhibition and venetoclax to treat patients with MCL.

PRMT5 supports multiple oncogenic pathways in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an incurable B-cell malignancy with an overall poor prognosis, particularly for patients that progress on targeted therapies. Novel, more durable treatment options are needed for patients with MCL. Protein arginine methyltransferase 5 (PRMT5) is overexpressed in MCL and plays an important oncogenic role in this disease via epigenetic and posttranslational modification of cell cycle regulators, DNA repair genes, components of prosurvival pathways, and RNA splicing regulators. The mechanism of targeting PRMT5 in MCL remains incompletely characterized. Here, we report on the antitumor activity of PRMT5 inhibition in MCL using integrated transcriptomics of in vitro and in vivo models of MCL. Treatment with a selective small-molecule inhibitor of PRMT5, PRT-382, led to growth arrest and cell death and provided a therapeutic benefit in xenografts derived from patients with MCL. Transcriptional reprograming upon PRMT5 inhibition led to restored regulatory activity of the cell cycle (p-RB/E2F), apoptotic cell death (p53-dependent/p53-independent), and activation of negative regulators of B-cell receptor-PI3K/AKT signaling (PHLDA3, PTPROt, and PIK3IP1). We propose pharmacologic inhibition of PRMT5 for patients with relapsed/refractory MCL and identify MTAP/CDKN2A deletion and wild-type TP53 as biomarkers that predict a favorable response. Selective targeting of PRMT5 has significant activity in preclinical models of MCL and warrants further investigation in clinical trials.

CdGAP promotes prostate cancer metastasis by regulating epithelial-to-mesenchymal transition, cell cycle progression, and apoptosis.

High mortality of prostate cancer patients is primarily due to metastasis. Understanding the mechanisms controlling metastatic processes remains essential to develop novel therapies designed to prevent the progression from localized disease to metastasis. CdGAP plays important roles in the control of cell adhesion, migration, and proliferation, which are central to cancer progression. Here we show that elevated CdGAP expression is associated with early biochemical recurrence and bone metastasis in prostate cancer patients. Knockdown of CdGAP in metastatic castration-resistant prostate cancer (CRPC) PC-3 and 22Rv1 cells reduces cell motility, invasion, and proliferation while inducing apoptosis in CdGAP-depleted PC-3 cells. Conversely, overexpression of CdGAP in DU-145, 22Rv1, and LNCaP cells increases cell migration and invasion. Using global gene expression approaches, we found that CdGAP regulates the expression of genes involved in epithelial-to-mesenchymal transition, apoptosis and cell cycle progression. Subcutaneous injection of CdGAP-depleted PC-3 cells into mice shows a delayed tumor initiation and attenuated tumor growth. Orthotopic injection of CdGAP-depleted PC-3 cells reduces distant metastasic burden. Collectively, these findings support a pro-oncogenic role of CdGAP in prostate tumorigenesis and unveil CdGAP as a potential biomarker and target for prostate cancer treatments.

Postoperative Urinary Retention Following General Anesthesia for Endoscopic Nasal Surgery in Men Aged Older Than 60 Years: A Retrospective Study.

OBJECTIVES: Postoperative urinary retention (POUR) is influenced by many factors, and its reported incidence rate varies widely. This study aimed to investigate the occurrence and risk factors for urinary retention following general anesthesia for endoscopic nasal surgery in male patients aged >60 years. METHODS: A retrospective review of medical records between January 2015 and December 2019 identified 253 patients for inclusion in our study. Age, body mass index (BMI), a history of diabetes/hypertension, American Society of Anesthesiologists (ASA) classification, and urologic history were included as patient-related factors. Urologic history was subdivided into 3 groups according to history of benign prostate hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and current medication. The following was analyzed as perioperative variables for POUR development: duration of anesthesia and surgery; amount of fluid administered; rate of fluid administration; intraoperative requirement for fentanyl, ephedrine, and dexamethasone; postoperative pain; and analgesic use. Preoperatively measured prostate size and uroflowmetry parameters of patients on medication for symptoms were compared according to the incidence of urinary retention. RESULTS: Thirty-seven (15.7%) patients developed POUR. Age (71.4 vs 69.6 years), BMI (23.9 vs 24.9 kg/m2), a history of diabetes/hypertension, ASA classification, and perioperative variables were not significantly different between patients with and without POUR. Only urologic history was identified as a factor affecting the occurrence of POUR (P = .03). The incidence rate among patients without urologic issues was 5.9%, whereas that among patients with BPH/LUTS history was 19.8%. Among patients taking medication for symptoms, the maximal and average velocity of urine flow were significantly lower in patients with POUR. CONCLUSIONS: General anesthesia for endoscopic nasal surgery may be a potent trigger for urinary retention in male patients aged >60 years. The patient's urological history and urinary conditions appear to affect the occurrence of POUR.

Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of blood cancers arising in lymphoid tissues that commonly effects both humans and dogs. Protein arginine methyltransferase 5 (PRMT5), an enzyme that catalyzes the symmetric di-methylation of arginine residues, is frequently overexpressed and dysregulated in both human solid and hematologic malignancies. In human lymphoma, PRMT5 is a known driver of malignant transformation and oncogenesis, however, the expression and role of PRMT5 in canine lymphoma has not been explored. To explore canine lymphoma as a useful comparison to human lymphoma while validating PRMT5 as a rational therapeutic target in both, we characterized expression patterns of PRMT5 in canine lymphoma tissue microarrays, primary lymphoid biopsies, and canine lymphoma-derived cell lines. The inhibition of PRMT5 led to growth suppression and induction of apoptosis, while selectively decreasing global marks of symmetric dimethylarginine (SDMA) and histone H4 arginine 3 symmetric dimethylation. We performed ATAC-sequencing and gene expression microarrays with pathway enrichment analysis to characterize genome-wide changes in chromatin accessibility and whole-transcriptome changes in canine lymphoma cells lines upon PRMT5 inhibition. This work validates PRMT5 as a promising therapeutic target for canine lymphoma and supports the continued use of the spontaneously occurring canine lymphoma model for the preclinical development of PRMT5 inhibitors for the treatment of human NHL.

Intraglandular Ordinary Lipoma of the Submandibular Gland.

Lipomas are the most common soft tissue lesions occurring in the salivary glands but have a very low incidence. Lipomas commonly occur in the parotid gland, and lipomas in the submandibular gland (SMG) are rare. Until recently, ordinary lipomas of the parotid gland and some variants of lipomas of the SMG have been reported. However, few reports of ordinary lipomas occurring within the SMG exist in the literature. We report an extremely rare case of ordinary lipoma within the right SMG of a 65-year-old man. The tumor measured a 2.0 × 1.8 × 2.7 cm, was a well-capsulated homogenous yellow mass, which was composed of mature adipose tissue. A partially mixed area with salivary gland tissue was observed. There has not been much research on lipomatous tumors from the SMG because of their rareness. Most lipomatous tumors in the parotid gland are known as ordinary lipomas, but more research is needed to determine whether they can be applied to the SMG. Thus, this report will be instrumental in the understanding of lipomatous tumors of the SMG.

Transducin ß-like protein 1 controls multiple oncogenic networks in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common Non-Hodgkin's lymphoma and is characterized by a remarkable heterogeneity with diverse variants that can be identified histologically and molecularly. Large-scale gene expression profiling studies have identified the germinal center B-cell (GCB-) and activated B-cell (ABC-) subtypes. Standard chemo-immunotherapy remains standard front line therapy, curing approximately two thirds of patients. Patients with refractory disease or those who relapse after salvage treatment have an overall poor prognosis highlighting the need for novel therapeutic strategies. Transducin ß-like protein 1 (TBL1) is an exchange adaptor protein encoded by the TBL1X gene and known to function as a master regulator of the Wnt signalling pathway by binding to ß-CATENIN and promoting its downstream transcriptional program. Here, we show that, unlike normal B-cells, DLBCL cells express abundant levels of TBL1 and its overexpression correlates with poor clinical outcome regardless of DLBCL molecular subtype. Genetic deletion of TBL1 and pharmacological approach using tegavivint, a first-in-class small molecule targeting TBL1 (Iterion Therapeutics), promotes DLBCL cell death in vitro and in vivo. Through an integrated genomic, biochemical, and pharmacologic analyses, we characterized a novel, ß-CATENIN independent, post-transcriptional oncogenic function of TBL1 in DLBCL where TBL1 modulates the stability of key oncogenic proteins such as PLK1, MYC, and the autophagy regulatory protein BECLIN-1 through its interaction with a SKP1-CUL1-F-box (SCF) protein supercomplex. Collectively, our data provide the rationale for targeting TBL1 as a novel therapeutic strategy in DLBCL.

Postoperative expressive aphasia associated with intravenous midazolam administration: a 5-year retrospective case-control study.

OBJECTIVES: This study aimed to investigate the epidemiology of intravenous midazolam-induced postoperative expressive aphasia (EA). METHODS: The incidence rate, risk ratio, and contributing factors to intravenous midazolam-induced postoperative EA were analyzed retrospectively in 6756 orthopedic patients. A telephone interview was conducted with patients with EA after surgery. RESULTS: Patients were allocated to either the midazolam group (n = 6178) or no-midazolam group (n = 578). Twelve patients developed EA in the midazolam group, with an incidence of 0.19%, and no patient developed EA in the no-midazolam group. The mean age of EA patients was 70 years, and 92% were women. Among them, 75% received general anesthesia, and the mean dose of midazolam was 1.8 mg. EA was reversed in nine of 12 (75%) patients within 4 minutes of flumazenil administration, and >60 minutes were required to reverse EA in the other three patients (25%). CONCLUSION: Intravenous midazolam administration for preoperative sedation caused transient EA in 0.19% of patients, especially elderly women who received general anesthesia, and EA could be reversed by flumazenil.

Eagle syndrome after a fracture of complete ossified stylohyoid ligament from indirect trauma treated using local steroid injection: A case report.

RATIONALE: Stylohyoid complex syndrome is characterized by various cervicopharyngeal symptoms related to the ossification and abnormality of the styloid process, stylohyoid ligament, and the lesser horn of the hyoid bone. Eagle syndrome is the most well-known of the spectra of these diseases. Although surgical treatment is considered effective, conservative treatment may be beneficial if symptoms arise because of inflammation of the soft tissues attached to the styloid process or hyoid bone. PATIENT CONCERNS: A 68-year-old man presented with pain in the right side of the neck and odynophagia after trauma on his philtrum. He was diagnosed with Eagle syndrome elicited by a fracture from indirect trauma. Despite analgesic medication and physiotherapy, the pain had somewhat relieved but persisted for 1 year. DIAGNOSIS: Computed tomography revealed complete ossification of the bilateral stylohyoid complex. A fracture was observed in the ampulla on the right side of the neck. One year later, the fracture resolved by complete union. INTERVENTIONS: Ultrasonography was performed and abnormal ossification was observed on the right side of the neck. Five milligrams of dexamethasone at a concentration of 1 kg/m was slowly injected into the tender point under ultrasonographic guidance. OUTCOMES: The patient reported immediate reduction of pain and was satisfied with the resolution. No recurrence was observed during a 6-month follow-up period. LESSONS: Although traumatic fracture of the ossified ligament elicited the syndrome, the results were satisfactory because the origin of the patient's pain was presumed to arise from inflammatory conditions. This case demonstrates that treatment with local steroid injection may be appropriate for patients who present with pain originating from muscles and ligaments.

Protein arginine methyltransferase 5 represses tumor suppressor miRNAs that down-regulate CYCLIN D1 and c-MYC expression in aggressive B-cell lymphoma.

Protein arginine methyltransferase-5 (PRMT5) is overexpressed in aggressive B-cell non-Hodgkin's lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma, and supports constitutive expression of CYCLIN D1 and c-MYC. Here, we combined ChIP analysis with next-generation sequencing to identify microRNA (miRNA) genes that are targeted by PRMT5 in aggressive lymphoma cell lines. We identified enrichment of histone 3 dimethylation at Arg-8 (H3(Me2)R8) in the promoter regions of miR33b, miR96, and miR503. PRMT5 knockdown de-repressed transcription of all three miRNAs, accompanied by loss of recruitment of epigenetic repressor complexes containing PRMT5 and either histone deacetylase 2 (HDAC2) or HDAC3, enhanced binding of co-activator complexes containing p300 or CREB-binding protein (CBP), and increased acetylation of specific histones, including H2BK12, H3K9, H3K14, and H4K8 at the miRNA promoters. Re-expression of individual miRNAs in B-cell lymphoma cells down-regulated expression of PRMT5, CYCLIN D1, and c-MYC, which are all predicted targets of these miRNAs, and reduced lymphoma cell survival. Luciferase reporter assays with WT and mutant 3'UTRs of CYCLIN D1 and c-MYC mRNAs revealed that binding sites for miR33b, miR96, and miR503 are critical for translational regulation of the transcripts of these two genes. Our findings link altered PRMT5 expression to transcriptional silencing of tumor-suppressing miRNAs in lymphoma cells and reinforce PRMT5's relevance for promoting lymphoma cell growth and survival.

The erector spinae plane block for effective analgesia after lung lobectomy: Three cases report.

RATIONALE: The thoracic epidural block and thoracic paravertebral block are widely used techniques for multimodal analgesia after thoracic surgery. However, they have several adverse effects, and are not technically easy. Recently, the erector spinae plane block (ESPB), an injected local anesthetic deep to the erector spinae muscle, is a relatively simple and safe technique. PATIENT CONCERNS: Three patients were scheduled for video assisted thoracoscopic lobectomy with mediastinal lymph node dissection. All the patients denied any past medical history to be noted. DIAGNOSES: They were diagnosed with primary adenocarcinoma requiring lobectomy of lung. INTERVENTIONS: The continuous ESPB was performed at the level of the T5 transverse process. The patient was received the multimodal analgesia consisted of oral celecoxib 200 mg twice daily, intravenous patient-controlled analgesia (Fentanyl 700 mcg, ketorolac 180 mg, total volume 100 ml), and local anesthetic (0.375% ropivacaine 30 ml with epinephrine 1:200000) injection via indwelling catheter every 12 hours for 5 days. Additionally, we injected a mixture of ropivacaine and contrast through the indwelling catheter for verifying effect of ESPB and performed Computed tomography 30 minutes later. OUTCOMES: The pain score was maintained below 3 points for postoperative 5 days, and no additional rescue analgesics were administered during this period. In the computed tomography, the contrast spread laterally from T2-T12 deep to the erector spinae muscle. On coronal view, the contrast spread to the costotransverse ligament connecting the rib and the transverse process. In the 3D reconstruction, the contrast spread from T6-T10 to the costotransverse foramen. LESSONS: Our contrast imaging data provides valuable information about mechanism of ESPB from a living patient, and our report shows that ESPB can be a good option as a multimodal analgesia after lung lobectomy.

Multimodal analgesia with multiple intermittent doses of erector spinae plane block through a catheter after total mastectomy: a retrospective observational study.

BACKGROUND: Although case reports have suggested that the erector spinae plane block (ESPB) may help analgesia for patients after breast surgery, no study to date has assessed its effectiveness. This retrospective observational study analyzed the analgesic effects of the ESPB after total mastectomy. METHODS: Forty-eight patients were divided into an ESPB group (n = 20) and a control group (n = 28). Twenty patients in the control group were selected by their propensity score matching the twenty patients in the ESPB group. Patients in the ESPB group were injected with 30 mL 0.375% ropivacaine, followed by catheter insertion for further injections of local anesthetics every 12 hours. Primarily, total fentanyl consumption was compared between the two groups during the first 24 hours postoperatively. Secondary outcomes included pain intensity levels (visual analogue scale) and incidence of postoperative nausea and vomiting (PONV). RESULTS: Median cumulative fentanyl consumption during the first 24 hours was significantly lower in the ESPB (33.0µg; interquartile range [IQR], 27.0-69.5µg) than in the control group (92.8µg; IQR, 40.0-155.0µg) (P = 0.004). Pain level in the early postoperative stage (<3 hr) and incidence of PONV (0% vs. 55%) were also significantly lower in the ESPB group compared to the control (P = 0.001). CONCLUSIONS: Intermittent ESPB after total mastectomy reduces fentanyl consumption and early postoperative pain. ESPB is a good option for multimodal analgesia after breast surgery.

Extended Stability of Reconstituted and Diluted SB3 (Trastuzumab Biosimilar) Assessed by Physicochemical and Biological Properties.

INTRODUCTION: Stability information for the trastuzumab biosimilar SB3 is limited to 48 h at 2-8 °C for the reconstituted solution and 24 h at up to 30 °C for diluted solutions. Extended physicochemical stability and biological activity were assessed to evaluate the advanced preparation of reconstituted and diluted SB3. METHODS: Under controlled and aseptic conditions, the stability of reconstituted and diluted SB3 was evaluated using several assessments and according to the UK's National Health Service guidance. Reconstituted SB3 was stored at 25 ± 2 °C with 60 ± 5% relative humidity for 3 days, and subsequently diluted SB3 (0.32-4 mg/mL) was stored in an infusion bag in the absence of light at 25 ± 2 °C with 60 ± 5% relative humidity for 28 days and 5 ± 3 °C for 28 days, respectively. Physicochemical stability (appearance, pH, protein concentration, size exclusion high-performance liquid chromatography, non-reducing capillary electrophoresis-sodium dodecyl sulfate, imaged capillary isoelectric focusing), biological activity (competitive inhibition binding assay to human epidermal growth factor receptor 2 by fluorescence resonance energy transfer, anti-proliferation assay), and properties with a potential safety impact (subvisible particulates, submicronic aggregation by dynamic light scattering) were determined. RESULTS: No physicochemical instability signs or biological activity changes were observed for either reconstituted or diluted SB3 up to 28 days; all stability acceptance criteria were met. No major change was noted in the proportion of molecular weight variants (high molecular weight impurity, total purity) or relative percentages of acidic, main, and basic charge isoforms of the protein. No increases in particulates or aggregates in terms of a potential safety impact were noted. CONCLUSION: The physicochemical stability and biological activity of reconstituted and diluted SB3 are maintained for extended time periods beyond those denoted in the product labeling, which allows for advanced SB3 preparation and may reduce drug wastage and preparation time. FUNDING: Samsung Bioepis Co., Ltd.

Erector spinae plane block for multimodal analgesia after wide midline laparotomy: A case report.

RATIONALE: The most commonly used regional techniques for analgesia following laparotomy thoracic epidural analgesia and paravertebral blocks are technically difficult to perform and carry a risk of severe complications. Recently, the erector spinae plane block (ESPB) has been reported to effectively treat neuropathic pain. The ultrasound-guided ESPB is an easily performed fascial plane block that can provide sensory blockade from T2-4 to T12-L1. Moreover, the ESPB reportedly blocks both the ventral rami of spinal nerves and the rami communicants, which contain sympathetic nerve fibres, through spread into the thoracic paravertebral space. PATIENT CONCERNS: We report the case of a 35-year-old female patient who underwent excision of a larger ovarian mass via laparotomy with a wide, midline incision from the xiphoid process to the pubic tubercle. DIAGNOSES: They were diagnosed with mucinous cystadenoma originated from the right ovary and fallopian tube, and a right oophorectomy and salpingectomy were performed. INTERVENTIONS: The ESPB was performed for postoperative pain control at the level of the T8 transverse process. Postoperative multimodal analgesia was provided according to the acute pain service protocol of our hospital. The patient was prescribed oral acetaminophen 175 mg every 6 hours and intravenous patient-controlled analgesia (PCA) with fentanyl 7 µg/mL. A 1:1 mixture of 0.75% ropivacaine (20 mL) and saline (20 mL) with epinephrine (1: 200,000) was manually injected through the indwelling catheter every 8 hours (20 mL per side). OUTCOMES: The first demand dose of fentanyl was administered at 9 hours and 39 minutes after the surgery. There were no reported resting pain scores >4, nor were any rescue analgesics needed during the first 5 postoperative days. LESSONS: The ESPB provided highly effective analgesia as a part of multimodal analgesia after laparotomy with a wide midline incision.

Protein arginine methyltransferase 5 (PRMT5) promotes survival of lymphoma cells via activation of WNT/ß-catenin and AKT/GSK3ß proliferative signaling.

Epigenetic regulation by the type II protein arginine methyltransferase, PRMT5, plays an essential role in the control of cancer cell proliferation and tumorigenesis. In this report, we investigate the relationship between PRMT5 and WNT/ß-CATENIN as well as AKT/GSK3ß proliferative signaling in three different types of non-Hodgkin's lymphoma cell lines, clinical samples, and mouse primary lymphoma cells. We show that PRMT5 stimulates WNT/ß-CATENIN signaling through direct epigenetic silencing of pathway antagonists, AXIN2 and WIF1, and indirect activation of AKT/GSK3ß signaling. PRMT5 inhibition with either shRNA-mediated knockdown or a specific small molecule PRMT5 inhibitor, CMP-5, not only leads to derepression of WNT antagonists and decreased levels of active phospho-AKT (Thr-450 and Ser-473) and inactive phospho-GSK3ß (Ser-9) but also results in decreased transcription of WNT/ß-CATENIN target genes, CYCLIN D1, c-MYC, and SURVIVIN, and enhanced lymphoma cell death. Furthermore, PRMT5 inhibition leads to reduced recruitment of co-activators CBP, p300, and MLL1, as well as enhanced recruitment of co-repressors HDAC2 and LSD1 to the WNT/ß-CATENIN target gene promoters. These results indicate that PRMT5 governs expression of prosurvival genes by promoting WNT/ß-CATENIN and AKT/GSK3ß proliferative signaling and that its inhibition induces lymphoma cell death, which warrants further clinical evaluation.

Evaluation of the physicochemical and biological stability of reconstituted and diluted SB2 (infliximab).

OBJECTIVES: To evaluate the critical quality attributes that might affect the stability of an infliximab biosimilar (SB2, Flixabi) when reconstituted or diluted and stored under refrigeration and at room temperature. METHODS: We largely adhered to the UK's National Health Service guidance requirements for the design of a robust stability study and for robust testing methods. Protocol components included evaluation of visual appearance, chemical stability, physical stability, pH, particle sizes and biological activity. The stability of reconstituted SB2 was assessed for 60 days at 5°C and for 7 days at 25°C. Stability of diluted SB2 at concentrations that ranged from 240 mg/250 mL (3 mg/kg; 80 kg patient) to 400 mg/250 mL (5 mg/kg; 80 kg patient) was assessed for 7 days at both temperatures. Dilutions were made in polyethylene bags containing 0.9% NaCl. Forced degradation studies were conducted with SB2 and its reference product (USA-sourced and European Union-sourced Remicade). Stress conditions of heat or light occurred before product reconstitution. RESULTS: In a laboratory environment under aseptic conditions, stability acceptance criteria with regard to physicochemical and biological properties were met for all reconstituted and diluted SB2 samples for all time periods and temperatures assessed. After either heat or light stress, similar stability and biological activity were noted for SB2 and both reference products. CONCLUSIONS: When prepared under aseptic conditions in accordance with the product's Summary of Product Characteristics, exposed for prolonged periods at 5°C and 25°C and assessed with the described methods, SB2 appears to remain a stable monoclonal antibody maintaining its expected biological function.