Immune prognostic score predicts the risk of infection and survival outcomes in patients with relapsed multiple myeloma treated with bispecific antibodies.

The Glasgow prognostic score (GPS) and CAR-HEMATOTOX (CAR-HT) score identify multiple myeloma (MM) patients at high risk for immune-mediated toxicity and early mortality with cellular immunotherapy. However, their association with outcomes in patients receiving T-cell redirecting bispecific antibodies (bsAb) is unclear. This multi-centre retrospective study examines the association of baseline GPS and CAR-HT scores with outcomes in 126 MM patients treated with bsAb. Overall, 19% were identified as GPS high risk but did not experience increased toxicity or mortality. Conversely, high-risk CAR-HT patients had a higher incidence of infections and inferior survival, suggesting a need for aggressive infection mitigation strategies.

Persistent opioid use in patients with multiple myeloma post-ASCT.

PURPOSE: Bone pain is a common presenting symptom of multiple myeloma (MM) and is frequently treated with opioids in addition to myeloma directed therapy. With improved response and survival with modern myeloma therapy, it is important to re-examine the role of opioids in managing symptomatic myeloma. PATIENTS AND METHODS: We performed a retrospective analysis of patients with myeloma at Rutgers Cancer Institute of New Jersey (RCINJ) who received an ASCT between January 1, 2012, and December 30, 2017, and who had subsequent follow-up (a total of 138 patients). We sought information specifically from the visits after induction therapy but prior to ASCT, at 100 days and 1-year post-ASCT follow-up visits. We compared opioid users and non-users in relation to treatment response, co-morbid conditions, and symptoms. We also examined amounts, duration, and odds of continued opioid use. RESULTS: At the time of the first analysis (before transplant), 34.8% of patients were using opioids and opioid use was more frequent in younger patients and, as expected, in patients with bone lesions. At 1 year, 31.9% of patients were still using opioids and continued opioid use was not correlated with disease response. Of the patients using opioids at the time of transplant, 58% either maintained their opioid dose or increased it at 1-year post-transplant. CONCLUSIONS: This retrospective analysis shows that despite a small decrease in opioid use over time, opioid use remains frequent in MM patients and is correlated with younger age and bone involvement but not with response to therapy. Over half the patients using opioids at the time of transplant continued or increased opioid use over the following year. With increasing survival in myeloma patients, further attention is required to distinguish cancer pain from chronic pain in cancer patients.

SARS-CoV-2 nosocomial infection: Real-world results of environmental surface testing from a large tertiary cancer center.

BACKGROUND: Despite consensus guidelines, concern about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has dissuaded patients with cancer from seeking medical care. Studies have shown that contaminated surfaces may contain viable virus for up to 72 hours in laboratory settings. The purpose of this study was to investigate contamination of SARS-CoV-2 on commonly used environmental surfaces in a tertiary cancer care center. METHODS: This study evaluated the incidence of SARS-CoV-2 viral RNA in high-touch outpatient and inpatient cancer center spaces. Surfaces were tested over a 2-week period after patient or staff exposure but before scheduled disinfection services according to the World Health Organization protocols for coronavirus disease 2019 (COVID-19) surface sampling. Samples were analyzed via reverse transcriptase-polymerase chain reaction for the presence of SARS-CoV-2 RNA. RESULTS: Two hundred four environmental samples were obtained from inpatient and outpatient oncology clinics and infusion suites, and they were categorized as 1) public areas, 2) staff areas, or 3) medical equipment. One hundred thirty surfaces from 2 outpatient hematology and oncology clinics and 36 surfaces from an inpatient leukemia/lymphoma/chimeric antigen receptor T-cell unit were examined, and all 166 samples were negative for SARS-CoV-2. One of 38 samples (2.6%) from COVID-19+ inpatient units was positive. Altogether, the positive test rate for SARS-CoV-2 RNA across all surfaces was 0.5% (1 of 204). CONCLUSIONS: This prospective, systematic quality assurance investigation of real-world environmental surfaces, performed in inpatient and outpatient hematology/oncology units, revealed overall negligible detection of SARS-CoV-2 RNA when strict mitigation strategies against COVID-19 transmission were instituted. LAY SUMMARY: The potential risks of nosocomial infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have deterred patients with cancer from seeking timely care despite consensus guidelines. This study has found negligible rates of environmental contamination with SARS-CoV-2 across a multitude of commonly used surfaces in outpatient and inpatient hematology/oncology settings with adherence to strict infection control protocols.

Lymphoma Occurring During Pregnancy: Current Diagnostic and Therapeutic Approaches.

PURPOSE OF REVIEW: Pregnancy-associated lymphoma (PAL) is an uncommon entity that lacks detailed prospective data. It poses significant management challenges that incorporate maternal and fetal risks associated with treatment or delayed intervention. Herein, we review the current literature for the diagnosis, management, and supportive care strategies for PAL. RECENT FINDINGS: Establishment of a multidisciplinary team, including hematology-oncology, maternal-fetal medicine, and neonatology, is critical in the management of PAL. For staging, ultrasound and MRI are preferred modalities with use of computerized tomography in select situations. Data for the safety and effectiveness of therapy for PAL is largely based on retrospective studies. The timing of lymphoma-directed antenatal systemic therapy depends on the trimester, gestational age, lymphoma subtype and aggressiveness, and patient wishes. Therapy in the first trimester is usually not advocated, while treatment in the second and third trimesters appears to result in similar outcomes for PAL compared with non-pregnant patients with lymphoma. An overarching goal in most PAL cases should be to plan for delivery at term (i.e., gestational age > 37 weeks). For supportive care, most antiemetics, including agents such as neurokinin-1 receptor antagonists, have been used safely during pregnancy. For prevention or treatment of infections, particular antibiotics (i.e., macrolides, cephalosporins, penicillins, metronidazole), antivirals (i.e., acyclovir, valacyclovir, famciclovir), and antifungals (amphotericin B) have demonstrated safety and with use of growth factors reserved for treatment of neutropenia (vs. primary prophylaxis). Therapy for PAL should be individualized with goals of care that balance maternal and fetal well-being, which should include a multidisciplinary care team and overall intent for term delivery in most cases.

Spectrin tetramer formation is not required for viable development in Drosophila.

The dominant paradigm for spectrin function is that (αß)2-spectrin tetramers or higher order oligomers form membrane-associated two-dimensional networks in association with F-actin to reinforce the plasma membrane. Tetramerization is an essential event in such structures. We characterize the tetramerization interaction between α-spectrin and ß-spectrins in Drosophila. Wild-type α-spectrin binds to both ß- and ßH-chains with high affinity, resembling other non-erythroid spectrins. However, α-spec(R22S), a tetramerization site mutant homologous to the pathological α-spec(R28S) allele in humans, eliminates detectable binding to ß-spectrin and reduces binding to ßH-spectrin ∼1000-fold. Even though spectrins are essential proteins, α-spectrin(R22S) rescues α-spectrin mutants to adulthood with only minor phenotypes indicating that tetramerization, and thus conventional network formation, is not the essential function of non-erythroid spectrin. Our data provide the first rigorous test for the general requirement for tetramer-based non-erythroid spectrin networks throughout an organism and find that they have very limited roles, in direct contrast to the current paradigm.

Protein trafficking abnormalities in Drosophila tissues with impaired activity of the ZIP7 zinc transporter Catsup.

Developmental patterning requires the precise interplay of numerous intercellular signaling pathways to ensure that cells are properly specified during tissue formation and organogenesis. The spatiotemporal function of the Notch signaling pathway is strongly influenced by the biosynthesis and intracellular trafficking of signaling components. Receptors and ligands must be trafficked to the cell surface where they interact, and their subsequent endocytic internalization and endosomal trafficking is crucial for both signal propagation and its down-modulation. In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila epithelial tissues, we recovered mutations that disrupt the Catsup gene, which encodes the Drosophila ortholog of the mammalian ZIP7 zinc transporter. Loss of Catsup function causes Notch to accumulate abnormally in the endoplasmic reticulum (ER) and Golgi compartments, resulting in impaired Notch signaling. In addition, Catsup mutant cells exhibit elevated ER stress, suggesting that impaired zinc homeostasis causes increased levels of misfolded proteins within the secretory compartment.

Therapeutic strategies for the treatment of tauopathies: Hopes and challenges.

A group of neurodegenerative diseases referred to as tauopathies are characterized by the presence of brain cells harboring inclusions of pathological species of the tau protein. These disorders include Alzheimer's disease and frontotemporal lobar degeneration due to tau pathology, including progressive supranuclear palsy, corticobasal degeneration, and Pick's disease. Tau is normally a microtubule (MT)-associated protein that appears to play an important role in ensuring proper axonal transport, but in tauopathies tau becomes hyperphosphorylated and disengages from MTs, with consequent misfolding and deposition into inclusions that mainly affect neurons but also glia. A body of experimental evidence suggests that the development of tau inclusions leads to the neurodegeneration observed in tauopathies, and there is a growing interest in developing tau-directed therapeutic agents. The following review provides a summary of strategies under investigation for the potential treatment of tauopathies, highlighting both the promises and challenges associated with these various therapeutic approaches.

Volvulus of the entire small bowel with normal bowel fixation simulating malrotation and midgut volvulus.

BACKGROUND: Midgut volvulus is a complication of malrotation of bowel and mesenteric malfixation. In contrast, primary volvulus of the small bowel is a distinctly different and rare entity characterized by torsion of the entire small bowel with normal mesenteric fixation. OBJECTIVE: To present the clinical and imaging findings in four infants with primary small bowel volvulus and normal bowel fixation in order to improve awareness of this entity among clinicians and radiologists and to discuss the potential etiologies of this entity to distinguish it from other causes of small bowel volvulus. MATERIALS AND METHODS: A retrospective review of imaging studies (two ultrasounds and four upper gastrointestinal series) in four infants (three full-term and one premature) from three institutions with surgically proven volvulus of the entire small bowel and normal bowel fixation were reviewed by three board-certified pediatric radiologists and correlated with clinical and surgical reports when available. RESULTS: The infants presented during the first week to 6 months of life and were acutely ill. The upper gastrointestinal series showed complete duodenal obstruction with beaking in one and partial duodenal obstruction in three. All studies were interpreted as highly suspicious for malrotation and midgut volvulus. Emergent laparotomy demonstrated primary small bowel volvulus with normal mesenteric fixation in all infants. The base of the small bowel mesentery was described by the operating surgeon as smaller than normal in one infant (case 3). There was no mesenteric defect or other abnormality predisposing to volvulus in the other three. In both infants who had abdominal US, a retroperitoneal position of the third portion of the duodenum was demonstrated. All infants survived. One infant required resection of the necrotic small bowel and currently has short gut syndrome, one has malabsorption and two were lost to follow-up. CONCLUSION: Primary small bowel volvulus with normal fixation is indistinguishable from malrotation with midgut volvulus in the acutely ill infant or child. Radiographic diagnosis can be difficult in patients with intermittent or incomplete small bowel volvulus without malrotation. In these patients, neither an upper gastrointestinal series demonstrating a normal position of the duodenojejunal junction nor the sonographic demonstration of a retromesenteric third portion of the duodenum excludes the diagnosis. In young infants, the clinical and imaging findings may mimic necrotizing enterocolitis. Sonography may be useful to evaluate the bowel for signs of bowel wall compromise or a whirlpool sign.

Linvoseltamab for Treatment of Relapsed/Refractory Multiple Myeloma.

PURPOSE: We present a phase I/II first-in-human trial evaluating the safety and efficacy of 50 mg and 200 mg doses of linvoseltamab, a B-cell maturation antigen × CD3 bispecific antibody in relapsed/refractory multiple myeloma (RRMM). METHODS: Phase II eligible patients had RRMM that either progressed on/after ≥three lines of therapy including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 antibody or was triple-class (PI/IMiD/anti-CD38) refractory. Phase II treatment was once a week through week 14 and then once every 2 weeks. Phase II 200 mg patients who achieved a ≥very good partial response by week 24 received linvoseltamab once every 4 weeks. The primary end point in phase II was overall response rate (ORR). RESULTS: Among the 117 patients treated with 200 mg, the median age was 70 years, 39% had high-risk cytogenetics, and 28% had penta-refractory disease. At a median follow-up of 14.3 months, the ORR was 71%, with 50% achieving ≥complete response (CR). In 104 patients treated with 50 mg at a median follow-up of 7.4 months, the ORR was 48%, with 21% achieving ≥CR. The median duration of response (DOR) for 200 mg patients (n = 83) was 29.4 months (95% CI, 19.2 to not evaluable). Among 200 mg patients, the most common adverse events included cytokine release syndrome (35.0% Gr1, 10.3% Gr2, 0.9% Gr3), neutropenia (0.9% Gr2, 18.8% Gr3, 23.1% Gr4), and anemia (3.4% Gr1, 4.3% Gr2, 30.8% Gr3). Immune effector cell-associated neurotoxicity syndrome occurred in 7.7% of patients (2.6% each Gr1, Gr2, Gr3). Infections were reported in 74.4% of patients (33.3% Gr3, 2.6% Gr4); infection frequency and severity declined over time. CONCLUSION: Linvoseltamab 200 mg induced deep and durable responses, with a median DOR of 29.4 months, in patients with RRMM with an acceptable safety profile.

Annexin B9 binds to ß(H)-spectrin and is required for multivesicular body function in Drosophila.

The role of the cytoskeleton in protein trafficking is still being defined. Here, we describe a relationship between the small Ca(2+)-dependent membrane-binding protein Annexin B9 (AnxB9), apical ß(Heavy)-spectrin (ß(H)) and the multivesicular body (MVB) in Drosophila. AnxB9 binds to a subset of ß(H) spliceoforms, and loss of AnxB9 results in an increase in basolateral ß(H) and its appearance on cytoplasmic vesicles that overlap with the MVB markers Hrs, Vps16 and EPS15. Similar colocalizations are seen when ß(H)-positive endosomes are generated either by upregulation of ß(H) in pak mutants or through the expression of the dominant-negative version of ß(H). In common with other mutations disrupting the MVB, we also show that there is an accumulation of ubiquitylated proteins and elevated EGFR signaling in the absence of AnxB9 or ß(H). Loss of AnxB9 or ß(H) function also causes the redistribution of the DE-Cadherin (encoded by shotgun) to endosomal vesicles, suggesting a rationale for the previously documented destabilization of the zonula adherens in karst (which encodes ß(H)) mutants. Reduction of AnxB9 results in degradation of the apical-lateral boundary and the appearance of the basolateral proteins Coracle and Dlg on internal vesicles adjacent to ß(H). These results indicate that AnxB9 and ß(H) are intimately involved in endosomal trafficking to the MVB and play a role in maintaining high-fidelity segregation of the apical and lateral domains.

Serum Immunoglobulin Levels as Potential Biomarkers of COVID-19 Pneumonia.

OBJECTIVE: Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) has been known to cause immune dysregulation. However, the association between specific immunoglobulins and clinical characteristics in COVID-19 remains poorly understood. This study investigated the relationship between immunoglobulins and clinical outcomes in adults hospitalized with COVID-19 pneumonia. METHODS: A retrospective chart analysis was performed (N=569, December 2020-April 2021). Information on demographics, clinical factors, and total serum immunoglobulin (IgG, IgA, IgM, and IgE) levels were collected (N=60). Clinical outcomes of interest included: symptom duration, comorbidities (Charlson 10-year-estimated-survival (C10YES) and comorbidity index (CCI), vital derangements upon presentation (NEWS-2-score), length of stay (LOS), and mortality. Spearman correlation, chi-square tests and linear regression were conducted. RESULTS: Serum IgM levels were positive predictors of C10YES (ß=0.104, p=0.023) and negative predictors of CCI (ß=-0.007, p=0.047). There was an association between higher serum IgG levels and longer LoS (ß=7.455, p=0.047). We found no significant associations between immunoglobulins and preadmission symptom duration, medication use, or mortality. CONCLUSIONS: Total IgM was associated with increased survival and decreased comorbidity, and total IgG was associated with length of hospitalization. IgM may predict the body's initial ability to produce humoral immune responses, and IgG may function as a possible signature of chronic antigenic responses and inflammation, associated with comorbidities that increase COVID-19 hospitalization. Evaluating total IgM and IgG as prognostic biomarkers in COVID-19 pneumonia patients may contribute to improved management and clinical outcomes.

Challenges and Opportunities in Antimicrobial Stewardship among Hematopoietic Stem Cell Transplant and Oncology Patients.

Antimicrobial stewardship programs play a critical role in optimizing the use of antimicrobials against pathogens in the era of growing multi-drug resistance. However, implementation of antimicrobial stewardship programs among the hematopoietic stem cell transplant and oncology populations has posed challenges due to multiple risk factors in the host populations and the infections that affect them. The consideration of underlying immunosuppression and a higher risk for poor outcomes have shaped therapeutic decisions for these patients. In this multidisciplinary perspective piece, we provide a summary of the current landscape of antimicrobial stewardship, unique challenges, and opportunities for unmet needs in these patient populations.

Understanding of molecular basis of histological graded horn cancer by transcriptome profiling.

Horn cancer is most devastating and prominent cancer in Indian zebu cattle that affects socio-economic condition of small-scale farmers who depends on their cattle for farm work. Development in the field for genomics through next generation sequencing and bioinformatics advancement have helped to identify genes which have a role in horn cancer development. Histopathological examination of cancerous tissues of horn revealed myxomatous changes, well, moderate and poorly differentiated squamous cell carcinoma. Differential gene expression analysis showed 40, 11, 66 and 29 upregulated genes and 10, 14, 08 and 07 down-regulated genes in myxomatous, well, moderate and poorly differentiated squamous cell carcinoma as compared to normal. Significant differentially expressed genes are related to cell development, cell proliferation, cell-cell communication, cell signaling and angiogenesis which are linked to Akt pathway, mTOR pathway and Wnt pathway. Activity of these genes and related pathways have already been established about their role in development of cancer. Among the candidate genes; keratin family, keratin family related gene, chemokine signaling and cytokines signaling associated genes could be a prominent target for the development of stage specific prognosis marker after further detailed study at large sample population level. CSTA, PTN, SPP1 genes have upregulation in all stages of cancer and they have enrolled as biomarkers for horn cancer.

Profiling of Antimicrobial Resistance Genes and Integron from Escherichia coli Isolates Using Whole Genome Sequencing.

This study is designed to investigate Escherichia coli for the antibiotic resistance genes (ARGs) and integrons from healthy as well as diarrhoeic/diseased animals/birds' faecal samples. A total of eight samples were selected for the study; from each animal, two samples were taken, one from healthy animals/birds and one from diarrhoeic/diseased animals/birds. Antibiotic sensitivity testing (AST) and whole genome sequencing (WGS) was performed for selected isolates. The E. coli isolates showed resistance to moxifloxacin, followed by erythromycin, ciprofloxacin, pefloxacin, tetracycline, levofloxacin, ampicillin, amoxicillin, and sulfadiazine (4/8, 50.00% each). The E. coli isolates were 100% sensitive to amikacin, followed by chloramphenicol, cefixime, cefoperazone, and cephalothin. A total of 47 ARGs from 12 different antibiotic classes were detected among the eight isolates by WGS. The different classes of antibiotics included aminoglycoside, sulphonamide, tetracycline, trimethoprim, quinolone, fosfomycin, phenicol, macrolide, colistin, fosmidomycin, and multidrug efflux. The class 1 integrons were detected in 6/8 (75.00%) isolates with 14 different gene cassettes.

COVID-19 Vaccine Responses in Patients With Plasma Cell Dyscrasias After Complete Vaccination.

INTRODUCTION: Due to functional hypogammaglobulinemia, patients with multiple myeloma are at increased risk for infection and generally have poorer responses to vaccines. In this study, we examined antibody responses after complete COVID-19 vaccination in patients with plasma cell dyscrasias, most of whom were receiving treatment. PATIENTS AND METHODS: Real world study of consecutive patients with multiple myeloma and other plasma cell dyscrasias (PCD) were evaluated after complete vaccination with either the 2-shot mRNA vaccines from BioNTech and Moderna or the 1-shot adenoviral vector vaccine from Johnson & Johnson (J&J). Patients received vaccines 1-4 months before antibody testing without controlling for the type of vaccine or the timing of drug therapy. Patients with a clinical history or antibody evidence of prior infection were excluded. Antinucleocapsid and quantitative anti-spike antibody levels were measured with the Roche Elecys assay. RESULTS: Ninety-five percent of patients had detectable antibody responses. Multivariate analysis showed that higher age, ongoing anti-CD38 monoclonal antibody therapy and the J&J vaccine negatively affected quantitative response. A small number of ineffectively vaccinated patients receiving IVIG subsequently had detectable nucleocapsid and spike antibodies confirming the presence of the latter in currently administered IVIG. CONCLUSIONS: Nearly all PCD had detectable anti-spike antibodies after vaccination but age, anti-CD38 monoclonal antibody therapy, and the single-shot J&J vaccine negatively affected responses. In patients who received the J&J vaccine, second doses or heterologous mRNA vaccines should be tested. Quantitative antibody testing might make future management more rational, particularly in patients with poor responses.

Improved outcomes using laparoscopy for emergency colectomy after mitigating bias by negative control exposure analysis.

BACKGROUND: Laparoscopy is superior to open surgery for elective colectomy, but its role in emergency colectomy remains unclear. Previous studies were small and limited by confounding because surgeons may have selected lower-risk patients for laparoscopy. We therefore studied the effect of attempting laparoscopy for emergency colectomies while adjusting for confounding using multiple techniques in a large, nationwide registry. METHODS: Using National Surgical Quality Improvement Program data, we identified emergency colectomy cases from 2014 to 2018. We first compared outcomes between patients who underwent laparoscopic versus open surgery, while adjusting for baseline variables using both propensity scores and regression. Next, we performed a negative control exposure analysis. By assuming that the group that converted to open did not benefit from the attempt at laparoscopy, we used the observed benefit to bound the effect of unmeasured confounding. RESULTS: Of 21,453 patients meeting criteria, 3,867 underwent laparoscopy, of which 1,375 converted to open. In both inverse probability of treatment weighting and regression analyses, attempting laparoscopy was associated with improved 30-day mortality, overall morbidity, anastomotic leak, surgical site infection, postoperative septic shock, and length of hospital stay compared with open surgery. These effects were consistent with the lower bounds computed from the converted group. CONCLUSION: Laparoscopic surgery for colorectal emergencies appears to improve outcomes compared with open surgery. The benefit is observed even after adjusting for both measured and unmeasured confounding using multiple statistical approaches, thus suggesting a benefit not attributable to patient selection.

Learning through a Pandemic: The Current State of Knowledge on COVID-19 and Cancer.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has left patients with current or past history of cancer facing disparate consequences at every stage of the cancer trajectory. This comprehensive review offers a landscape analysis of the current state of the literature on COVID-19 and cancer, including the immune response to COVID-19, risk factors for severe disease, and impact of anticancer therapies. We also review the latest data on treatment of COVID-19 and vaccination safety and efficacy in patients with cancer, as well as the impact of the pandemic on cancer care, including the urgent need for rapid evidence generation and real-world study designs. SIGNIFICANCE: Patients with cancer have faced severe consequences at every stage of the cancer journey due to the COVID-19 pandemic. This comprehensive review offers a landscape analysis of the current state of the field regarding COVID-19 and cancer. We cover the immune response, risk factors for severe disease, and implications for vaccination in patients with cancer, as well as the impact of the COVID-19 pandemic on cancer care delivery. Overall, this review provides an in-depth summary of the key issues facing patients with cancer during this unprecedented health crisis.

Immunotherapies Old and New: Hematopoietic Stem Cell Transplant, Chimeric Antigen Receptor T Cells, and Bispecific Antibodies for the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma.

PURPOSE OF REVIEW: Diffuse large B cell lymphoma (DLBCL) is curable in a majority of patients; however, a significant portion of patients develop relapsed or refractory disease. High-dose chemotherapy followed by autologous stem cell transplant is the standard approach in appropriately selected patients. Many patients are not candidates for transplant and many who do receive autologous transplant relapse. Therapies which harness T cells including chimeric antigen receptor T cells (CAR-T) and bispecific antibodies are active in this chemotherapy-resistant population. We review the role of autologous and allogeneic stem cell transplant, CAR-T therapy, and bispecific antibodies in the treatment of relapsed or refractory DLBCL. RECENT FINDINGS: Phase I studies of bispecific antibodies directed against CD20 × CD3 have shown activity in heavily pre-treated DLBCL including in patients who have progressed following autologous transplant and/or CAR-T therapy. Two CAR-T products have received regulatory approval in relapsed or refractory DLBCL, with other products in clinical trials. CAR-T treatment has resulted in durable remissions and trials are ongoing to determine if CAR-T should replace autologous transplant as second-line therapy for DLBCL. The development of multiple T cell-directed therapies for DLBCL offers new treatment options for chemotherapy-resistant disease. We discuss our approach to relapsed or refractory DLBCL patients and the open question of optimal sequencing of autologous transplant (a current standard treatment), CAR-T therapy (FDA approved), and bispecific antibodies (in clinical trials).

Emerging Needs and Viability of Telepsychiatry During and Post COVID-19 Era: A Literature Review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in nationwide stay-at-home orders in an effort to slow the spread severely impacting the healthcare sector. Telepsychiatry provides a platform bridging the gap through advanced technologies connecting mental health providers and patients who need their services, overcoming previous barriers of great distances, lack of transportation, and even time constraints. The most obvious benefit is increased accessibility to mental healthcare, especially in underserved and remote areas where there is no easy access for in-person care. It is important to note that benefits are not limited to patients, but also allow clinicians greater flexibility in scheduling and reduced practice overhead costs, both of which aid with physician burnout and burden. Telepsychiatry during COVID-19 provides its own unique advantages over in-person visits. The risk of exposure to healthcare workers and patients receiving care is reduced, allowing immunocompromised patients to receive much-needed psychiatric care. Without the need to meet in person, self-isolating psychiatrists can still provide care, decreasing strain on their co-workers. Although telepsychiatry is relatively new, it has already exhibited considerable success in its effectiveness at treating psychiatric conditions and widespread corollary benefits. Telepsychiatric consults may be carried out synchronously and asynchronously, each having benefits and setbacks. Different mobile application interventions have been explored, which are available for the purpose of both monitoring/assessing patients and/or providing treatment. The scope of conditions these applications address is broad, from anxiety disorders to schizophrenia to depression. As promising and beneficial telepsychiatry may seem, it is necessary to recognize that building the program can be challenging. It involves adapting to new methods in medicine. We highlighted barriers to general telepsychiatry, the most prominent being technological literacy of both physician and patient, and possible negative effects of eliminating the in-person patient-doctor interaction.

Towards a membrane proteome in Drosophila: a method for the isolation of plasma membrane.

BACKGROUND: The plasma membrane (PM) is a compartment of significant interest because cell surface proteins influence the way in which a cell interacts with its neighbours and its extracellular environment. However, PM is hard to isolate because of its low abundance. Aqueous two-phase affinity purification (2PAP), based on PEG/Dextran two-phase fractionation and lectin affinity for PM-derived microsomes, is an emerging method for the isolation of high purity plasma membranes from several vertebrate sources. In contrast, PM isolation techniques in important invertebrate genetic model systems, such as Drosophila melanogaster, have relied upon enrichment by density gradient centrifugation. To facilitate genetic investigation of activities contributing to the content of the PM sub-proteome, we sought to adapt 2PAP to this invertebrate model to provide a robust PM isolation technique for Drosophila. RESULTS: We show that 2PAP alone does not completely remove contaminating endoplasmic reticulum and mitochondrial membrane. However, a novel combination of density gradient centrifugation plus 2PAP results in a robust PM preparation. To demonstrate the utility of this technique we isolated PM from fly heads and successfully identified 432 proteins using MudPIT, of which 37% are integral membrane proteins from all compartments. Of the 432 proteins, 22% have been previously assigned to the PM compartment, and a further 34% are currently unassigned to any compartment and represent candidates for assignment to the PM. The remainder have previous assignments to other compartments. CONCLUSION: A combination of density gradient centrifugation and 2PAP results in a robust, high purity PM preparation from Drosophila, something neither technique can achieve on its own. This novel preparation should lay the groundwork for the proteomic investigation of the PM in different genetic backgrounds in Drosophila. Our results also identify two key steps in this procedure: The optimization of membrane partitioning in the PEG/Dextran mixture, and careful choice of the correct lectin for the affinity purification step in light of variations in bulk membrane lipid composition and glycosylation patterns respectively. This points the way for further adaptations into other systems.