Abstract Background and Aims Truxima is a biosimilar version of rituximab. It was licensed & launched in the United Kingdom in April 2017. A biosimilar medicine is made to be highly similar in quality, safety and efficacy to existing licensed “reference” biological medicine and the cost is often significantly lower. A recent systematic review showed comparable long-term efficacy and safety of biosimilar rituximab to the originator drug in treatment of rheumatoid arthritis and non-hodgkin’s lymphoma. Fewer data are available in regards to the efficacy of biosimilar rituximab in treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A retrospective study was thus conducted in our centre to examine the efficacy of Truxima when compared to the reference rituximab (MabThera) in the treatment of patients with AAV. Method All patients with new or relapsing AAV who received first ever rituximab therapy between 1/1/2016 and 31/12/2018 were identified via hospital dispensing database. Patients were stratified into Truxima or MabThera treatment group depending on the version of rituximab administered. Primary outcomes that were assessed include: time to B cell depletion (defined as absolute B cell count (ABC) ≤10) and repletion (i.e ABC >10 and >20); time to antimyeloperoxidase(MPO)/antiproteinase 3(PR3)-ANCA negativity; Secondary outcomes assessed include: overall survival, time to major relapse (defined as relapse requiring further course of rituximab for remission induction); adverse events including episodes of neutropenia, hypogammaglobulinemia and major infusion reactions. Subgroup analysis in patients who received concomitant cyclophosphamide and rituximab or other induction therapy was performed to examine if it impacts on the treatment efficacy. Results 59 and 60 patients received Truxima and MabThera respectively for treatment of new or relapsing AAV. The baseline characteristic (age, gender, entry estimated Glomerular Filtration Rate, proportion of patients received concomitant cyclophosphamide, ANCA serology and organ involvement) of both group were comparable. All patients achieved clinical remission following induction treatment. Using Kaplan Meier analysis and log rank test, no difference was identified in time to B cell depletion or repletion (Figure 1&2), MPO/PR3-ANCA negativity (Figure 3), overall survival or major relapses requiring further rituximab as induction therapy. Treatment efficacy of Truxima and MabThera did not differ in subgroup analysis. However we observed that patients who received concurrent cyclophosphamide during induction therapy achieved MPO/PR3-ANCA negativity more rapidly compared to those who did not irrespective of the version of rituximab received. No difference in adverse events such as major infusion reactions was seen in either group upon first rituximab exposure. Two patients in each group developed reactions following repeated dosing of rituximab. Conclusion Biosimilar rituximab Truxima appears to have comparable treatment efficacy compared to the reference drug in our cohort of patients with AAV.
Purpose: To review an unusual case of rapidly progressive sclerosing mesenteritis. Methods: Review of a clinical case. Results: A 50-year-old man presented with a three day history of nausea, retching, diffuse abdominal pain and abdominal distention. He was febrile to 102.4 F with a white blood cell count of 12.8 cells / mm3 and had loose stools; Clostridium difficile toxin was positive. Initial CT scan suggested enteritis. Despite treatment with oral vancomycin and intravenous metronidazole, over the following ten days, the patient remained febrile, continued to complain of abdominal pain and distention and became tachycardic and tachypneic. Endotracheal intubation was performed for progressive respiratory failure from a possible pneumonia. The abdomen was diffusely distended and tender. Eleven days after initial presentation, a repeat CT scan of the abdomen (figure) was performed which showed a large soft tissue mass in the small bowel mesentery and mesenteric adenopathy suggestive of extensive sclerosing mesenteritis. Laboratory data was remarkable for an albumin of 1.4 grams / deciliter, C-reactive protein of 67 mg/L, and erythrocyte sediment rate of 120 mm / hour. CT-guided core needle biopsy showed adipose tissue with fat necrosis and mixed inflammatory infiltrate, consistent with a diagnosis of sclerosing mesenteritis. The patient was treated with intravenous methylprednisolone 60 mg twice daily with dramatic clinical response within 24 hours, including resolution of fevers, extubation, and improvement in abdominal pain and distention. After five days, the methylprednisolone dose was decreased to 30 mg twice daily, tamoxifen 10 mg twice daily was added and the patient was discharged in good condition. Conclusion: Conclusions: Sclerosing mesenteritis is an idiopathic disease usually affecting Caucasian males in the fifth to seventh decade of life. An association between Clostridium difficile enteritis and sclerosing mesenteritis has not been reported previously. While published cases suggest that sclerosing mesenteritis usually presents insidiously, our case demonstrates that sclerosing mesenteritis should be considered in patients with unexplained, rapidly progressive abdominal pain and distention.
Introduction: Transplantation-mediated alloimmune thrombocytopenia (TMAT) is a rare form of passenger lymphocyte syndrome in which lymphocytes from the donor organ produce antibodies against recipient platelets resulting in thrombocytopenia. We describe a novel treatment of TMAT with efgartigimod, a human IgG1 Fc antibody fragment, in a patient with severe, refractory thrombocytopenia following liver transplantation. Case Description/Methods: A 70-year-old man with cirrhosis secondary to non-alcoholic steatohepatitis complicated by hepatocellular carcinoma underwent deceased donor orthotopic liver transplantation. He required emergent retransplantation on post-operative day 7 for acute hepatic artery thrombosis. Seven days after retransplantation, the patient developed severe thrombocytopenia with platelets <1 × 109/L. He responded poorly to platelet transfusion, and two days later developed severe intra-abdominal bleeding requiring exploratory laparotomy. No active bleeding was found, and splenectomy was performed. Testing for heparin induced thrombocytopenia was negative, and the working diagnoses were post transfusion purpura and idiopathic thrombocytopenic purpura. Over the next 8 weeks, the patient had persistent, severe thrombocytopenia despite platelet transfusions and treatment with intravenous immunoglobulin, plasmapheresis, rituximab, romiplostim, and eltrombopag. Notably, two patients who received lung and kidney transplants from the same donor also developed severe thrombocytopenia. Ultimately, testing revealed the presence of serum antibodies to human platelet antigen (HPA) 1a. Genetic testing revealed the genotypes HPA 1a/1b and HPA 1b/1b in the patient and donor respectively, consistent with a mismatch and TMAT. The patient received weekly efgartigimod for 4 doses, and after his third infusion developed sustained improvement in platelets to >100 × 109/L without need for transfusion. Discussion: TMAT is a rare disorder after solid organ transplantation that can lead to severe thrombocytopenia with life threatening bleeding and even death. Although TMAT generally resolves a few months after transplantation as donor lymphocytes are cleared from the circulation, initial management is challenging. Efgartigimod is a novel treatment approved by the food and drug administration for myasthenia gravis that leads to degradation of IgG by binding to the neonatal Fc receptor and should be considered for severe TMAT.
Photoreceptors are coupled via gap junctions in many mammalian species. Cone-to-cone coupling is thought to improve sensitivity and signal-to-noise ratio, while rod-to-cone coupling provides an alternative rod pathway active under twilight or mesopic conditions (Smith et al., 1986; DeVries et al., 2002; Hornstein et al., 2005). Gap junctions are composed of connexins, and connexin36 (Cx36), the dominant neuronal connexin, is expressed in the outer plexiform layer. Primate (Macaca mulatta) cone pedicles, labeled with an antibody against cone arrestin (7G6) were connected by a network of fine processes called telodendria and, in double-labeled material, Cx36 plaques were located precisely at telodendrial contacts between cones, suggesting strongly they are Cx36 gap junctions. Each red/green cone made nonselective connections with neighboring red/green cones. In contrast, blue cone pedicles were smaller with relatively few short telodendria and they made only rare or equivocal Cx36 contacts with adjacent cones. There were also many smaller Cx36 plaques around the periphery of every cone pedicle and along a series of very fine telodendria that were too short to reach adjacent members of the cone pedicle mosaic. These small Cx36 plaques were closely aligned with nearly every rod spherule and may identify sites of rod-to-cone coupling, even though the identity of the rod connexin has not been established. We conclude that the matrix of cone telodendria is the substrate for photoreceptor coupling. Red/green cones were coupled indiscriminately but blue cones were rarely connected with other cones. All cone types, including blue cones, made gap junctions with surrounding rod spherules.
ObjectiveTo report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes.MethodsWe conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models.ResultsA total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19–directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care.ConclusionMayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic.
e24104 Background: There is a high rate of anemia present in cancer patients and anemia is also a common referral to a hematologist. Symptomatic anemia can significantly impair an individual’s functional status so identifying its cause is essential for improving quality of life. Correction of nutritional deficiencies, like iron, B12, and folate deficiency can improve hemoglobin counts, prevent recurrent PRBC transfusions, and can often resolve the anemia. In a busy academic hematology oncology practice, we hypothesize that it is easy to overlook performing a basic nutritional evaluation especially in the setting of other causes for anemia such as chemotherapy, hemolysis, blood loss, chronic kidney disease, and other disorders. We aim to evaluate the frequency of anemia workup in the hematology and oncology division at our academic institution. Methods: We conducted a retrospective study of all hematology oncology patients seen in our clinic who received a blood transfusion in 2021. All patients were 18 years old or order and received at least one-unit PRBC transfusion as an outpatient. One “transfusion event” was defined as any number of PRBC transfusions on a single day and any subsequent transfusions within a 90-day periods. A single patient, therefore, can have multiple distinct transfusion events. We analyzed whether patients received a “basic” anemia evaluation, defined as checking ferritin, iron saturation, B12, and folate levels within 3 months before or after the first transfusion, and whether a discrepancy in practice patterns exists between different hematology oncology subspecialties. Results: At the interim analysis, we identified 368 transfusion events for 275 patients. Those events were ordered by providers (physician, nurse practitioner, or physician assistant) in the following subspecialties: oncology (n = 20), malignant hematology (n = 18), classical hematology (n = 3), and fellow-in-training (n = 5). A basic anemia workup was missing in 58% (84 of 146), 27% (49 of 183), 23% (8 of 35), 40% (2 of 5) in the above groups respectively. For patients with macrocytic anemia defined as mean corpuscular volume (MCV) > 100 fL, 48% (38 of 79) did not have B12 or folate levels checked within 3 months before or after a transfusion event. For patients with MCV < 80 fL, 47% (14 of 30) did not have ferritin or iron saturation checked within 3 months before or after a transfusion event. Conclusions: We observed a high percentage of cancer and non-malignant hematology patients who did not receive a basic anemia evaluation within three months before or three months after a blood transfusion. A higher percentage of patients with solid tumors patients who required PRBC transfusions did not receive a basic anemia evaluation in a timely manner. Our study identified an area of quality improvement and need for intervention that can easily be overlooked in a busy academic hematology oncology practice.
Gap junctions are abundant in the mammalian retina and many neuronal types form neural networks. Several different neuronal connexins have now been identified in the mammalian retina. Cx36 supports coupling in the AII amacrine cell network and is essential for processing rod signals. Cx36 is probably also responsible for photoreceptor coupling. Horizontal cells appear to be extensively coupled by either Cx50 or Cx57. These results indicate that multiple neuronal connexins are expressed in the mammalian retina and that different cell types express different connexins.
Abstract Background Platelet transfusion carries risk of transfusion‐transmitted infection (TTI). Pathogen reduction of platelet components (PRPC) is designed to reduce TTI. Pulmonary adverse events (AEs), including transfusion‐related acute lung injury and acute respiratory distress syndrome (ARDS) occur with platelet transfusion. Study design An open label, sequential cohort study of transfusion‐dependent hematology‐oncology patients was conducted to compare pulmonary safety of PRPC with conventional PC (CPC). The primary outcome was the incidence of treatment‐emergent assisted mechanical ventilation (TEAMV) by non‐inferiority. Secondary outcomes included: time to TEAMV, ARDS, pulmonary AEs, peri‐transfusion AE, hemorrhagic AE, transfusion reactions (TRs), PC and red blood cell (RBC) use, and mortality. Results By modified intent‐to‐treat (mITT), 1068 patients received 5277 PRPC and 1223 patients received 5487 CPC. The cohorts had similar demographics, primary disease, and primary therapy. PRPC were non‐inferior to CPC for TEAMV (treatment difference −1.7%, 95% CI: (−3.3% to −0.1%); odds ratio = 0.53, 95% CI: (0.30, 0.94). The cumulative incidence of TEAMV for PRPC (2.9%) was significantly less than CPC (4.6%, p = .039). The incidence of ARDS was less, but not significantly different, for PRPC (1.0% vs. 1.8%, p = .151; odds ratio = 0.57, 95% CI: (0.27, 1.18). AE, pulmonary AE, and mortality were not different between cohorts. TRs were similar for PRPC and CPC (8.3% vs. 9.7%, p = .256); and allergic TR were significantly less with PRPC ( p = .006). PC and RBC use were not increased with PRPC. Discussion PRPC demonstrated reduced TEAMV with no excess treatment‐related pulmonary morbidity.
