ABSTRACT
Little is known about the central nervous system (CNS) risk in high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS). Hence, we sought to describe the rates of baseline CNS involvement, risk of CNS recurrence after primary therapy, and management strategies in HGBL, NOS. In this multicenter retrospective study, we included 160 adults with newly diagnosed HGBL, NOS treated between 2016 and 2021 at 20 US institutions. Eleven patients (7%) had baseline CNS involvement at diagnosis (leptomeningeal=6, parenchymal=4, and both=1). Baseline CNS involvement was significantly associated only with MYC rearrangement (OR=3.5) and testicular (in men) or female pelvic (in women) involvement (OR=8.1). There was no significant difference in survival outcomes between HGBL, NOS patients with (median PFS=4 years) or without (median PFS=2.4 years) baseline CNS involvement (p=0.45). The cumulative incidence of CNS recurrence at 3 years was 11%. Patients with baseline CNS involvement were at the highest risk (48.5% versus 8% for those without baseline CNS involvement) and were excluded from the risk factors analysis for CNS recurrence. The risk for CNS recurrence was significantly associated with blood or bone marrow involvement, CD5 expression, non-GCB subtype, and DEL phenotype, however, high CNS-IPI was not. The prognosis of relapsed HGBL, NOS was poor, regardless of whether recurrence was systemic or limited to the CNS, and with currently available salvage strategies, including autologous transplantation and CAR T-cell modalities, almost all patients with CNS recurrence ultimately succumbed to their disease. These patients represent an unmet need and should be prioritized for experimental approaches.
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Small bowel diverticulosis is not a common disease entity; however, it is increasingly diagnosed and linked to various gastrointestinal complaints. Although rare, complications can occur and may sometimes require surgical or endoscopic intervention. Furthermore, suspecting and diagnosing duodenal diverticulosis (DD) can be challenging due to the variety of presenting signs and symptoms. Much of our current knowledge comes from case reports and series. This report aims to document a case of DD presenting with severe right upper quadrant pain mimicking the signs and symptoms of acute cholecystitis. It also reviews and summarizes the available literature on the clinical manifestations of DD, its diagnostic approach, treatment modalities, and possible complications encountered in the ED.
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Single molecule fluorescence in situ hybridization (smFISH) and in situ hybridization chain reaction (HCR) have become powerful tools to visualize gene expression in many different animal species. We show here that smFISH and in situ HCR can be put to effective use in the satellite nematode model organism Pristionchus pacificus . Examining the expression of a homeobox gene ( Ppa-unc-30) , we found that HCR is more sensitive than smFISH. We confirmed the robustness of HCR by visualization of the expression of several genes involved in neurotransmitter synthesis or transport ( Ppa-unc-25 /GAD, Ppa-unc-17/VAChT, Ppa-eat-4 /VGLUT). Combined with its relative cost-effectiveness compared to smFISH analysis, in situ HCR constitutes a useful addition to the toolbox for P. pacificus research .
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The spectrum of indications for primary caesarean section changes with advancing parity. As parity advances more cesarean section are done for maternal rather than fetal indications. The objective of this study was to determine the indications and complications of caesarean section in multiparous women with history of previous vaginal delivery. This cross-sectional descriptive observational study was conducted in Mymensingh Medical College Hospital from January 2019 to June 2019 among 100 purposively selected multiparous women who underwent primary caesarean section. A well-designed, semi-structured questionnaire was used to collect data by face-to-face interview, clinical examinations and laboratory investigations. Data analysis was conducted in SPSS 20.0 version. Majority (74.0%) of the women in this study were in the age group 21-30 years with mean age of 26.3±5.76 years. Majority of the patients were of second gravida (42.0%) followed by third gravida (33.0%). The highest gravida in this study was 6th. Most of the patients were of para 1(44.0%). Highest para in this study was para 5. The most common indication of caesarean section in this study was foetal distress (26.0%). The next common indications were cephalo-pelvic disproportion (22.0%), antepartum haemorrhage (13.0%), mal-presentaion or mal-position (16.0%). Other causes were PROM (8.0%), prolonged labour (6.0%), cord prolapse (2.0%), post-dated pregnancy (4.0%), severe pre-eclampsia (2.0%) and secondary subfertility (1.0%). There was no case of maternal mortality in this study but 15 mothers suffered from various post-operative complications like wound infection (4.0%), UTI (4.0%), puerperal pyrexia (3.0%), postpartum haemorrhage (3.0%) and paralytic ileus (1.0%). Among the babies delivered 97 were live births. Among the 97 live births 11(11.34%) were preterm babies. Among the babies delivered majority (85.0%) was with good APGAR score (7-10). In conclusion it can say that a multiparous women in labour requires the same attention as that of primigravida. A parous women needs good obstetric care to improve maternal and neonatal outcome and still keeping caesarean section to a lower rate.
Subject(s)
Cesarean Section , Parity , Postoperative Complications , Tertiary Care Centers , Humans , Female , Adult , Cesarean Section/statistics & numerical data , Cesarean Section/adverse effects , Pregnancy , Cross-Sectional Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Tertiary Care Centers/statistics & numerical data , Young Adult , Fetal Distress/surgery , Fetal Distress/epidemiology , Cephalopelvic Disproportion/surgery , Cephalopelvic Disproportion/epidemiologyABSTRACT
Canada welcomes a large number of newcomers every year including international students and their families. The over 800,000 international students who arrived in Canada in 2022, are twice as likely to face difficulties in accessing healthcare services compared to those who were born in Canada. Lack of access to healthcare services may jeopardize their full participation in Canadian society. Pharmacists are highly accessible healthcare providers due to their regular contact with the public, extended working hours, and wide distribution of pharmacies. Given the expanding role of pharmacists in Canada, pharmacists can be a great resource for international newcomers to address their healthcare needs when transitioning to the Canadian healthcare system and exploring available services. In this study, we will explore how international students and their families, who make up a significant segment of newcomers to Canada each year, transition to Canada's healthcare system and identify their main challenges related to developing coping skills for managing diseases and navigating the complexities of prescription and nonprescription medication use. To do so, we will conduct virtual interviews with newcomer international students who have lived experience with transitioning to the Canadian healthcare system. This study will help understand the international student experience and identify how pharmacists can deliver a tailored package of pharmaceutical services to this population to best address their healthcare needs when transitioning to the Canadian healthcare system with the goal of reducing healthcare gaps and inequities. By exploring the healthcare challenges faced by these students, our findings will help pinpoint precise areas where pharmacists can practice to their full scope including medication management, patient education, and transitional care. Consequently, the study will offer detailed recommendations on how pharmacists can better support this population and thereby help alleviate the overall strain on the primary healthcare system.
Subject(s)
Delivery of Health Care , Pharmacists , Qualitative Research , Humans , Canada , Pharmacists/psychology , Students/psychology , Professional Role , Health Services Accessibility , Female , MaleABSTRACT
INTRODUCTION: Diabetes Mellitus is the metabolic disorder most prevalent globally, accounting for a substantial morbidity rate. The conventional drugs available for the management of diabetes are either expensive or lack the required efficacy. The purpose of this research is to isolate and characterize an active phytoconstituent from Coccinia grandis and assess its anti-diabetic properties. METHODS AND MATERIALS: Stems of Coccinia grandis are subjected to successive extraction and isolation. The isolated compound by column chromatography was characterized by FTIR (fourier-transform infrared), 1â¯H NMR (proton nuclear magnetic resonance), and Mass spectroscopy. The antidiabetic potential of the isolated compound was evaluated by in-vitro alpha-amylase inhibitory activity. Further, the compound was subjected to molecular docking studies to study its interaction with the human pancreatic alpha-amylase (Molegro Virtual Docker) as well to determine the pharmacokinetic and toxicity profile using computational techniques (OSIRIS property explorer, Swiss ADME, pkCSM, and PreADMET). RESULTS: The characterization of the compound suggests the structure to be 2,4-ditertiary butyl phenol. The in-vitro alpha-amylase inhibitory study indicated a concentration-dependent inhibition and the IC50 (median lethal dose) value of the isolated compound was found to be 64.36⯵g/ml. The docking study with the A chain of receptor 5EMY yielded a favorable docking score of -81.48 Kcal mol-1, suggesting that the compound binds to the receptor with high affinity through electrostatic, hydrophobic, and hydrogen bonds. Furthermore, the silico ADME analysis of the compound revealed improved metabolism, a skin permeability of -3.87â¯cm/s, gastrointestinal absorption of 95.48â¯%, and a total clearance of 0.984â¯logâ¯ml min-1 kg-1. In silico toxicity analysis also predicted cutaneous irritations but no carcinogenicity, mutagenicity, or hepatotoxicity. CONCLUSION: The data suggested that the isolated compound (2, 4-tertiary butyl phenol) has the potential to inhibit the alpha-amylase activity and possess optimal ADME properties as well as tolerable side effects.
Subject(s)
Molecular Docking Simulation , Phenols , alpha-Amylases , Humans , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/metabolism , Phenols/chemistry , Phenols/pharmacology , Phenols/isolation & purification , Cucurbitaceae/chemistry , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/isolation & purification , Molecular Structure , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/isolation & purificationABSTRACT
Ingestion or aspiration of dental implant screwdrivers or implant components is potentially life-threatening. There are no reports on the frequency at which dentists drop these devices within the mouth or which components are most problematic. There are few reports on what protective measures clinicians take, where risks exist, and how this problem is managed. A 9-part questionnaire was provided to dentists. Data collected included clinicians' roles, implant surgeons, restorative clinicians, or both-the frequency of dropping implant screwdrivers or components, items considered most problematic. Patient protection and management were also requested. Finally, questions related to how much of a problem clinicians considered this to be and if further solutions and a standardized management protocol should be developed. One hundred twelve dentists voluntarily completed the survey. Of the dentists, 54% restored, 37% restored and surgically placed, and 9% solely placed implants. Twenty-nine percent claimed never to drop components, with 56% dropping an instrument less than 10% of the time. Less than half would suggest patients seek medical advice if a screwdriver or component was accidentally dropped intraorally and was not recovered. Thirty percent never tied floss tethers to screwdrivers, and a similar percentage reported they only sometimes did so. Throat pack protection was reported 51% of the time. Ninety percent considered dropping components an issue, with screwdrivers most problematic. Aspiration or ingestion of implant screwdrivers and components is problematic, with dentists varying their use of protection devices. There is a need to standardize and implement patient protection procedures and management and develop methods to reduce the risk of these potentially life-threatening issues.
Subject(s)
Dental Implants , Humans , Surveys and Questionnaires , DentistsABSTRACT
Human papillomavirus (HPV)-positive oropharyngeal carcinoma is a distinct type of head and neck carcinoma with improved prognosis. p16 immunostaining is often used as a surrogate marker for HPV infection in this particular setting. The aim of this study is to estimate the prevalence of p16 staining and HPV infection in head and neck sarcomatoid carcinomas as well as head and neck sarcomas. 21 sarcomatoid carcinomas and 28 head and neck sarcomas were tested for p16 positivity using immunohistochemical staining, and for high-risk HPV infection using In situ hybridization (ISH). 24 % of sarcomatoid carcinomas and 21 % of sarcomas were positive for p16 staining. All 49 cases were negative for HPV ISH. The results confirm that p16 staining is not specific and may not be associated with HPV infection in non-oropharyngeal head and neck sites. They also indicate that non-oropharyngeal head and neck sarcomatoid carcinomas are not likely to be HPV related.
Subject(s)
Cyclin-Dependent Kinase Inhibitor p16 , Head and Neck Neoplasms , In Situ Hybridization , Papillomavirus Infections , Sarcoma , Humans , Head and Neck Neoplasms/virology , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/metabolism , Papillomavirus Infections/virology , Papillomavirus Infections/complications , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Male , Female , Middle Aged , Sarcoma/virology , Sarcoma/pathology , Sarcoma/metabolism , Aged , Immunohistochemistry/methods , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/analysis , Adult , Aged, 80 and over , Papillomaviridae/isolation & purificationABSTRACT
ABSTRACT: Bispecific antibodies (BsAb) that target CD3 and CD20 represent a new milestone in the treatment of patients with B-cell non-Hodgkin lymphoma. These drugs have demonstrated remarkable single-agent activity in patients with heavily pretreated disease, and 3 drugs have so far received regulatory approvals in various countries. However, BsAbs can potentially lead to severe toxicity associated with T-cell activation, particularly cytokine release syndrome (CRS). The anticipated widespread use of these off-the-shelf products poses challenges for implementation and highlights the need for guidance in anticipating, mitigating, and managing adverse events. In clinical trials, guidance for the evaluation and treatment of CRS and neurotoxicity associated with BsAb therapy has been modeled after algorithms originally created for chimeric antigen receptor (CAR) T-cell therapies and other immune effector therapies, yet notable differences in timing, quality, and severity exist between the toxicities of BsAbs and CAR T-cell therapies. We therefore convened an international panel of academic and community practice physicians, advanced practitioners, registered nurses, and pharmacists with experience using CD3×CD20 BsAbs in clinical trial and off-trial settings to provide comprehensive, consensus-based recommendations specific to the assessment and management of CD3×CD20 BsAb-related toxicities.
Subject(s)
Antibodies, Bispecific , Humans , Antibodies, Bispecific/therapeutic use , Consensus , Immunotherapy, Adoptive/adverse effects , Lymphocyte ActivationABSTRACT
Self-care is a growing area in community pharmacy globally. In a time where people are taking control over their own health care, the question of the degree of self-care available from community pharmacies is pertinent. New Zealand is a country that has publicly funded healthcare; with over 1000 community pharmacies catering to a population of 5 million people. Despite the availability and accessibility of community pharmacies, much remains unknown about how self-care is offered in community pharmacies and the extent to which it is provided. In addition to this lack of clarity, is the current period of reorganisation occurring in the New Zealand healthcare system. The current changes involve dis-establishing district health boards (DHBs) and unifying the New Zealand health system into one streamlined system. It leads us to question whether this move will change funding allocations and health priorities as well as how they affect service provision in community pharmacy. While research has shown that New Zealand is paving the way in medicines reclassification making medicines more accessible, other research shows a fragmentation exists in services provided by community pharmacies in the area of self-care. This article will highlight what is currently known about self-care in New Zealand, the gaps that exist and the current challenges in this area.
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ABSTRACT: CD30-positive primary cutaneous lymphoproliferative disorders (CD30 + PCLPD) are a heterogeneous group of cutaneous T-cell lymphoma (CTCL) that includes lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma. They exist as a clinical and pathological spectrum, which display significant overlap and variability. The diagnosis is made based on correlation between clinical and histopathologic findings. LyP with 6p25.3 rearrangement subtype represents <5% of LyP cases and is defined by DUSP22-IRF4 rearrangement on 6p25.3 locus. The reported cases express the alpha/beta T-cell receptor and follow an indolent clinical behavior typical of LyP. The same rearrangement is detected in 28% of anaplastic large cell lymphoma. We hereby present an extraordinary case of CD30 + PCLPD with DUSP22-IRF4 rearrangement and novel expression of gamma/delta T-cell immunophenotype in a young patient. Although the gamma/delta T-cell immunophenotype has been described in many other T-cell lymphomas, this is the first reported association with CD30 + PCLPD with DUSP22-IRF4 rearrangement.
Subject(s)
Lymphoma, T-Cell, Cutaneous , Lymphomatoid Papulosis , Humans , Female , Adult , Ki-1 Antigen , Lymphoma, T-Cell, Cutaneous/diagnosis , Lymphoma, T-Cell, Cutaneous/genetics , Gene Rearrangement , Lymphomatoid Papulosis/diagnosis , Lymphomatoid Papulosis/genetics , Intraepithelial LymphocytesABSTRACT
Background: Evidence exists of pharmacists providing free or partially subsidised clinical services in order to meet patient healthcare needs. Little is known about how patients perceive the quality and importance of such unfunded services to their healthcare. Objectives: To explore pharmacy user perspectives about unfunded services such as their valuation, why they chose to access these services from the pharmacy as well as their willingness to pay should pharmacies need to start charging for the provision of such services owing to budgetary constraints. Methods: This study was nested in a larger nationwide study where 51 pharmacies were recruited across fourteen locations across New Zealand . Semi-structured interviews were conducted with patients who had accessed unfunded services in community pharmacies. Patients were followed up to identify their percieved health outcomes resulting from accessing the unfunded service. Results: A total of 253 patient interviews were conducted on-site across 51 pharmacies in New Zealand. Two main themes were identified pertaining to (1) patient-provider relationship and (2) Willingness to pay. A total of fifteen different considerations were found to influence pharmacy users' decisions to access health services from the pharmacy. It was found that 62.8% of patients were willing to pay for unfunded services and the majority paying NZD$10. Conclusion: Patients positively rate these services and largely deem them important for their healthcare. Willingness to pay for services were also variable between patients and were dependant on the type of service accessed.
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ABSTRACT: Spindle cell lipoma (SCL) is a benign subcutaneous lipomatous neoplasm with a heterogeneous histologic appearance that varies greatly depending on the amount of fat, collagen, and myxoid stroma, which define the multiple subtypes of SCL, such as fat poor SCL, pseudoangiomatous SCL, and dendritic fibromyxolipoma. Cutaneous lymphoid hyperplasia is a spectrum of benign conditions characterized by reactive B-cell and T-cell cutaneous lymphocytic infiltrates. Cutaneous B-cell lymphoid hyperplasia is a heterogeneous group of non-neoplastic conditions that can be observed as reactive phenomena to infections, medications, allergens, or neoplasms and must be distinguished from cutaneous B-cell lymphomas. Here, we report a novel case of spindle cell lipoma, associated with B-cell primary lymphoid follicular hyperplasia, mixed within the tumor in a peculiar pattern, while discussing potential diagnostic pitfalls with low-grade B-cell lymphomas. This is the first report of such association in the literature.
Subject(s)
Lipoma , Lymphoma, B-Cell , Neoplasms, Connective Tissue , Skin Neoplasms , Humans , Hyperplasia , Lipoma/diagnosis , Lipoma/pathology , Skin Neoplasms/diagnosisABSTRACT
OBJECTIVES: An error in the diagnosis of an oral or maxillofacial lesion could potentially be detrimental to a patient's prognosis and management. Major discrepancies between the initial and subsequent diagnoses of head and neck pathologies range from 7 to 53%. This study determined the rate of discrepancies found in the diagnoses of oral and maxillofacial lesions after a second opinion in Saudi Arabia. METHODS: A retrospective single-center study was conducted by oral and maxillofacial pathology consultants to review all cases referred for a second opinion to the oral and maxillofacial pathology laboratory between January 2015 and December 2020. If the second-opinion diagnosis matched the original diagnosis, this was described as "agreement." If the second-opinion diagnosis did not match the original diagnosis but would not change the management or prognosis of a patient, this was classified as a "minor disagreement." If the second-opinion diagnosis resulted in the changing of a patient's management or prognosis, this was categorized as a "major disagreement." Chi-square test and Fisher's exact test were used to compare data between original and second-opinion diagnoses. A p-value of less than 0.05 was considered significant. RESULTS: Of 138 cases, 59 (43%) had an initial diagnosis and a second-opinion diagnosis that were in major disagreement. The most common tumor for which there was a major disagreement was squamous cell carcinoma. No single factor influenced the occurrence of major disagreements. CONCLUSIONS: Our evaluation reiterates the importance of obtaining a second opinion from a specialist in oral and maxillofacial pathology to improve the diagnostic accuracy for lesions. A formal system for this step, in addition to the obtaining of adequate clinical and radiographic information about a patient, is mandatory for the review of difficult cases.
Subject(s)
Carcinoma, Squamous Cell , Referral and Consultation , Humans , Retrospective Studies , Diagnostic Errors , PrognosisABSTRACT
OBJECTIVES: To examine the levels and socio-demographic differentials of: (a) reported COVID-like symptoms; and (b) seroprevalence data matched with COVID-like symptoms. METHODS: Survey data of reported COVID-like symptoms and seroprevalence were assessed by Roche Elecsys® Anti-SARS-CoV-2 immunoassay. Survey data of 10,050 individuals for COVID-like symptoms and seroprevalence data of 3205 individuals matched with COVID-like symptoms were analyzed using bivariate and multivariate logistic analysis. RESULTS: The odds of COVID-like symptoms were significantly higher for Chattogram city, for non-slum, people having longer years of schooling, working class, income-affected households, while for households with higher income had lower odd. The odds of matched seroprevalence and COVID-like symptoms were higher for non-slum, people having longer years of schooling, and for working class. Out of the seropositive cases, 37.77% were symptomatic-seropositive, and 62.23% were asymptomatic, while out of seronegative cases, 68.96% had no COVID-like symptoms. CONCLUSIONS: Collecting community-based seroprevalence data is important to assess the extent of exposure and to initiate mitigation and awareness programs to reduce COVID-19 burden.
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In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase >3 × upper limit of normal, and a dual-expressor immunophenotype. Age >60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS.
Subject(s)
Lymphoma, Large B-Cell, Diffuse , Humans , Middle Aged , Rituximab/therapeutic use , Retrospective Studies , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Prednisone/therapeutic use , Vincristine/therapeutic use , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-myc/genetics , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Etoposide , Lactate DehydrogenasesABSTRACT
Mantle cell lymphoma (MCL) is a rare, incurable hematological malignancy with a heterogeneous presentation and clinical course. A wide variety of chemotherapy-based regimens are currently used in patients who are untreated. Over the last several years, several targeted or small-molecule therapies have shown efficacy in the relapsed/refractory setting and have since been explored in the frontline setting. Lenalidomide plus rituximab was explored in a phase 2 study of 38 patients with MCL who were untreated and ineligible to receive transplantation, in which the combination produced durable remissions. We looked to build upon this regimen by adding venetoclax to the combination. We conducted a multicenter, open-label, nonrandomized, single-arm study to evaluate this combination. We enrolled 28 unselected patients with untreated disease irrespective of age, fitness, or risk factors. Lenalidomide was dosed at 20 mg daily from days 1 to 21 of each 28-day cycle. The dose of venetoclax was determined using the time-to-event continual reassessment method. Rituximab was dosed at 375 mg/m2 weekly, starting on cycle 1, day 1 until cycle 2, day 1. No dose-limiting toxicities were noted. All patients were treated with venetoclax at the maximum tolerated dose of 400 mg daily. The most common adverse events were neutropenia and thrombocytopenia. The overall and complete response rates were 96% and 86%, respectively. In total, 86% of patients achieved minimal residual disease undetectability via next-generation sequencing. The median overall and progression-free survivals were not reached. The combination of lenalidomide, rituximab, and venetoclax is a safe and effective regimen in patients with untreated MCL. This trial was registered at www.clinicaltrials.gov as #NCT03523975.
Subject(s)
Lymphoma, Mantle-Cell , Humans , Adult , Rituximab/adverse effects , Lenalidomide/therapeutic use , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Mantle-Cell/pathology , Bridged Bicyclo Compounds, Heterocyclic/adverse effectsABSTRACT
The interleukin-4 (IL-4) cytokine plays a critical role in modulating immune homeostasis. Although there is great interest in harnessing this cytokine as a therapeutic in natural or engineered formats, the clinical potential of native IL-4 is limited by its instability and pleiotropic actions. Here, we design IL-4 cytokine mimetics (denoted Neo-4) based on a de novo engineered IL-2 mimetic scaffold and demonstrate that these cytokines can recapitulate physiological functions of IL-4 in cellular and animal models. In contrast with natural IL-4, Neo-4 is hyperstable and signals exclusively through the type I IL-4 receptor complex, providing previously inaccessible insights into differential IL-4 signaling through type I versus type II receptors. Because of their hyperstability, our computationally designed mimetics can directly incorporate into sophisticated biomaterials that require heat processing, such as three-dimensional-printed scaffolds. Neo-4 should be broadly useful for interrogating IL-4 biology, and the design workflow will inform targeted cytokine therapeutic development.
Subject(s)
Cytokines , Interleukin-4 , Animals , Signal TransductionABSTRACT
ABSTRACT: Lichen planus pemphigoides (LPPemph), apart from bullous pemphigoid, is a rare bullous dermatosis that can be induced by programmed cell death protein-1 (PD-1)/PD ligand 1 (PD-L1) inhibitors. The primary location of PD-1/PD-L1 inhibitor-induced LPPemph has previously only been reported at the nonfollicular dermal-epidermal junction. We present a case of nivolumab-induced LPPemph with an intense perifollicular lichenoid reaction, prominent multifocal perifollicular clefting, which in addition, was also accompanied by linear IgG and C3 immunofluorescence deposits along the dermal-epidermal junction as well as demonstrating a perifollicular pattern. Intriguingly, the serological study of BP180 and BP230 antibodies was negative, suggesting the presence of additional novel antibodies, which primarily favor hair follicles and may contribute to the pathogenesis. Therefore, we consider this entity a novel variant of PD-1/PD-L1 inhibitor-induced bullous dermatosis. To the best of our knowledge, this is the first report that highlights perifollicular bullae accompanied by immunofluorescence findings in a PD-1/PD-L1 inhibitor-induced lesion. We propose a new immunotherapy associated entity, lichen planopilaris pemphigoides, and emphasize the significance of perifollicular changes in the pathogenesis.