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1.
J Invertebr Pathol ; : 108166, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39004164

RESUMO

Peptidoglycan recognition proteins (PGRPs) and Toll-like receptors (TLRs) are highly conserved pattern recognition receptors (PRRs). Earthworms possess genes encoding TLRs that specifically respond to Gram-positive bacteria. In addition, several PGRPs have been recently identified, which are predicted to exhibit amidase activity but lack receptor function. In lophotrochozoans, a membrane-bound PRR responsible for detecting Gram-negative bacteria remains unidentified. This study reveals several novel transmembrane peptidoglycan recognition proteins (Ean-PGRPLs) in earthworms, whose mRNA expression increases in response to Gram-negative but not Gram-positive bacteria. This indicates that Ean-PGRPLs may serve as a PRR associated with intracellular signaling for Gram-negative bacteria.

2.
Can Urol Assoc J ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39037505

RESUMO

INTRODUCTION: Accurate diagnostic staging of upper tract urothelial cancer (UTUC) is challenging. Endoscopic staging is limited by its ability to provide adequate sampling of deeper layers of the ureter and renal pelvis. Further ability to accurately predict invasive disease would aid in better selecting the appropriate treatment for patients. We aimed to analyze the ability of preoperative cross-sectional radiologic findings to predict pathologic outcomes, including tumor grade, muscle-invasive disease, and presence of lymphovascular invasion (LVI). METHODS: All patients diagnosed with localized UTUC (cN0M0) who underwent nephroureterectomy between February 2012 and December 2018 in Manitoba, Canada, were identified. Preoperative radiologic characteristics, including the presence and severity of hydronephrosis, as well as tumor location were recorded. Patients' and pathologic characteristics were also recorded. Logistic regression analysis was used to assess the association between radiologic variables and pathologic outcomes at radical surgery. RESULTS: A total of 112 pathology reports of patients with UTUC were obtained. The median age was 70 years (range 50-87), and 58.8% of patients were men. On univariate analysis, ureteric location on computed tomography (odds ratio [OR] 2.240, 95% confidence interval [CU] 1.049- 4.783, p=0.037) and presence of hydronephrosis (OR 2.455, 95% CI 1.094-5.506, p=0.0029) were each independently associated with locally invasive disease (>pT2). No radiologic variables were found to be a predictor of adverse pathology on multivariable analysis. Only the presence of hydronephrosis was associated with high-grade disease on univariate analysis (OR 2.533, 95% CI 1.083-5.931, p=0.032). CONCLUSIONS: Our findings suggest a limited role for cross-sectional imaging in predicting the presence of high-grade disease, LVI, or locally advanced disease in UTUC.

3.
Can Urol Assoc J ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39037507

RESUMO

INTRODUCTION: Amidst substantial surgical waitlists, novel methods are needed to improve the delivery of surgical care in Canada. One strategy involves shifting select surgeries from hospitals into community ambulatory centers, which expedite procedures and allow hospitals to prioritize critical and complex patients. We sought to evaluate surgical outcomes at a novel Canadian urologic clinic and surgical center. METHODS: A retrospective study was conducted at a novel accredited surgical facility and outpatient ambulatory clinic from August 2022 to August 2023. Procedures ranged from scrotal and transurethral surgeries to inflatable penile prosthesis insertion. Traditional outpatient procedures, including vasectomy and cystoscopy, were excluded. All patients were discharged the same day and seen 4-6 weeks post-procedure. Variables of interest included surgery type, anesthesia administered, additional clinic appointments, unplanned family physician appointments, visits to the emergency department (ED), and hospital admissions. RESULTS: In a 12-month period, 519 surgeries were performed. The mean patient age was 49.6±17.3 years, with most classified as American Society of Anesthesiologists (ASA) 1-2 (88.8%). Most (95.8%, n=497) patients did not require medical care outside the clinic before scheduled followup; 2.5% (n=13) visited the ED presenting for wound concerns, postoperative pain, query infection, or catheter-related concerns. Only 1.7% (n=9) required an unscheduled appointment with their family physician, with concerns being inadequate postoperative pain management (n=4) or suspected infection (n=4). No patient required hospital admission. CONCLUSIONS: Many urologic surgeries classically performed in hospital operating rooms can be safely performed in a non-hospital, outpatient surgical facility with preservation of good outcomes. This strategy can potentially improve the efficiency of urologic healthcare delivery in select patients.

4.
Urology ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972394

RESUMO

OBJECTIVE: To evaluate the effectiveness of Eutectic Mixture of Local Anesthetic (EMLA), a topical anesthetic cream, in office-based invasive andrological procedures such as hydrocelectomy, spermatocelectomy, and others, aimed at minimizing pain perception and enhancing the overall patient experience. METHODS: A double-blinded randomized controlled trial was conducted for patients undergoing scrotal andrology surgeries under LA. Power calculation was performed with an estimated sample size of 72. Participants were randomly assigned in a 1:1 ratio to topical EMLA + LA versus LA alone. In the post-operative recovery area, patient will be asked to complete a VAS questionnaire rating pain with LA administration and pain with procedure. Analysis comparing VAS pain scores of both groups was performed using the independent sample t-test method. RESULTS: Seventy-two patients were included in our analysis, with 36 in the control and 36 in the intervention arm. For patient pain with administration of LA, the control arm reported an average VAS pain score of 4.31, compared to 3.72 in the intervention arm (P = .319). For patient pain with procedure, patients in the control arm reported a median VAS pain score of 3.47 compared to 3.03 (P = .432) in the intervention arm. Overall, 86% (62/72) of patients reported that they would either be "very likely" (4/5) or "highly likely" (5/5) to undergo future procedures under local anesthetic. CONCLUSION: While performing scrotal surgeries under LA appears to be well tolerated and a feasible option, the application of EMLA cream does not appear to significantly alter patient-reported outcomes.

5.
Clin Nucl Med ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38861407

RESUMO

ABSTRACT: A 17-year-old boy with Von Hippel-Lindau syndrome presented with hypertension, raised plasma catecholamines, and MRI findings of a new pancreatic tail lesion and 2 stable right adrenal lesions concerning for functional neuroendocrine tumors. A 68Ga-DOTATATE PET/CT demonstrated intense tracer avidity within the pancreatic lesion with minimal uptake in the adrenal lesions. Conversely, a 123I-MIBG SPECT/CT study demonstrated high-grade tracer uptake within the adrenal lesions, with no significant uptake appreciated in the pancreatic lesion. The adrenal lesions were resected, and pathology was consistent with pheochromocytoma. Plasma catecholamines returned to within the normal range and hypertension resolved.

6.
Can Urol Assoc J ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38896478

RESUMO

INTRODUCTION: We aimed to investigate the surgical outcomes following inguinal and subinguinal urological procedures under deep intravenous sedation (DIVS) with multimodal local anesthesia (LA). METHODS: We conducted a retrospective cohort study from September 2022 to December 2023 including adult patients deemed eligible for day surgery (American Society of Anesthesiologist score 1-3) undergoing radical orchiectomy (RO), microscopic varicocelectomy (MV), or microscopic denervation of spermatic cords (MDSC). All procedures were performed at a single urologic ambulatory surgical center and outpatient clinic, and by a single surgeon (PP). Procedures were performed through a subinguinal or inguinal approach with DIVS and adjunctive multimodal LA. We evaluated intraoperative complications and relevant surgical outcomes and parameters. RESULTS: A total of 103 patients were included in the analysis with a mean age ± standard deviation of 37.3±9.6. This included 25 patients who underwent RO, 54 patients who underwent MV, and 24 patients who underwent MDSC. All procedures were completed successfully without intraoperative complications. Oncologic outcomes were preserved, fertility outcomes improved, and pain scores reduced similar to the expected rates in the literature. CONCLUSIONS: Our preliminary results demonstrate the safety, effectiveness, and feasibility of performing inguinal and subinguinal urologic procedures under DIVS with LA. These findings suggest that this technique preserves high-quality care while avoiding unnecessary risks of general or spinal anesthesia, representing an opportunity to transfer these cases outside of hospitals' operating rooms into outpatient ambulatory centers.

7.
Emerg Med J ; 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38825364

RESUMO

People experiencing the highest levels of social deprivation are more likely to present to emergency care across the spectrum of disease severity, and to have worse outcomes following acute illness. Emergency medicine in the UK and Europe has lagged behind other regions in incorporating social emergency medicine into practice. There is evidence that emergency clinicians have the potential to mitigate health inequalities, through advocacy and intervention supported by high-quality research, while also acknowledging the limitations intrinsic to the environment in which they work.

8.
Res Sq ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38883739

RESUMO

Lenalidomide maintenance is associated with a significantly improved progression-free in patients with newly diagnosed multiple myeloma. Maintenance with lenalidomide is generally well tolerated; however, lenalidomide associated diarrhea is a common side effect and bile acid malabsorption has been suggested as an underlying mechanism. We conducted a single arm phase 2 trial of colesevelam, a bile acid binder, for lenalidomide-associated diarrhea in multiple myeloma. Patients were treated with colesevelam daily starting at 1250 mg (2 tablets 625 mg) for 12 weeks. The trial included 25 patients, 1 patient with grade 3 diarrhea, 14 with grade 2, and 10 with grade 1 diarrhea. All patients were on treatment with single agent lenalidomide maintenance and no patient progressed during the trial. Colesevelam treatment was highly effective for treatment of lenalidomide-associated diarrhea; 22 (88%) of the 25 patients responded where 17 patients (68%) had complete resolution of diarrhea, and 5 patients (20%) had improvement by 1 grade of diarrhea. The responses to colesevelam were seen within the first two weeks of treatment. These findings support the conclusion that lenalidomide-associated diarrhea is driven by bile acid malabsorption. Five patients reported mild gastrointestinal side effects including constipation. Importantly, the pharmacokinetics of lenalidomide were not affected by concomitant colesevelam treatment. The stool microbiome composition was not significantly different before and after colesevelam treatment. Patients reported improved diarrhea, fewer gastrointestinal symptoms, and less interference with their daily life after starting colesevelam. In summary, colesevelam was safe and highly effective for treatment of lenalidomide-associated diarrhea in multiple myeloma and does not reduce the clinical effect of lenalidomide.

9.
Epilepsia ; 65(7): 2099-2110, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38752982

RESUMO

OBJECTIVE: Seizures can be difficult to control in infants and toddlers. Seizures with periods of apnea and hypoventilation are common following severe traumatic brain injury (TBI). We previously observed that brief apnea with hypoventilation (A&H) in our severe TBI model acutely interrupted seizures. The current study is designed to determine the effect of A&H on subsequent seizures and whether A&H has potential therapeutic implications. METHODS: Piglets (1 week or 1 month old) received multifactorial injuries: cortical impact, mass effect, subdural hematoma, subarachnoid hemorrhage, and seizures induced with kainic acid. A&H (1 min apnea, 10 min hypoventilation) was induced either before or after seizure induction, or control piglets received subdural/subarachnoid hematoma and seizure without A&H. In an intensive care unit, piglets were sedated, intubated, and mechanically ventilated, and epidural electroencephalogram was recorded for an average of 18 h after seizure induction. RESULTS: In our severe TBI model, A&H after seizure reduced ipsilateral seizure burden by 80% compared to the same injuries without A&H. In the A&H before seizure induction group, more piglets had exclusively contralateral seizures, although most piglets in all groups had seizures that shifted location throughout the several hours of seizure. After 8-10 h, seizures transitioned to interictal epileptiform discharges regardless of A&H or timing of A&H. SIGNIFICANCE: Even brief A&H may alter traumatic seizures. In our preclinical model, we will address the possibility of hypercapnia with normoxia, with controlled intracranial pressure, as a therapeutic option for children with status epilepticus after hemorrhagic TBI.


Assuntos
Apneia , Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , Hipoventilação , Convulsões , Animais , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/fisiopatologia , Suínos , Convulsões/etiologia , Convulsões/fisiopatologia , Hipoventilação/terapia , Hipoventilação/fisiopatologia , Hipoventilação/etiologia , Apneia/fisiopatologia , Eletroencefalografia , Fatores de Tempo , Ácido Caínico , Masculino
10.
J Foot Ankle Surg ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38789076

RESUMO

Ankle osteoarthritis (OA) is a debilitating condition that arises as a result of trauma or injury to the ankle and often progresses to chronic pain and loss of function that may require surgical intervention. Total ankle arthroplasty (TAA) has emerged as a means of operative treatment for end-stage ankle OA. Increased hospital length of stay (LOS) is a common adverse postoperative outcome that increases both the complications and cost of care associated with arthroplasty procedures. The purpose of this study was to employ four machine learning (ML) algorithms to predict LOS in patients undergoing TAA using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. The ACS-NSQIP database was queried to identify adult patients undergoing elective TAA from 2008 to 2018. Four supervised ML classification algorithms were utilized and tasked with predicting increased hospital length of stay (LOS). Among these variables, female sex, ASA Class III, preoperative sodium, preoperative hematocrit, diabetes, preoperative creatinine, other arthritis, BMI, preoperative WBC, and Hispanic ethnicity carried the highest importance across predictions generated by 4 independent ML algorithms. Predictions generated by these algorithms were made with an average AUC of 0.7257, as well as an average accuracy of 73.98% and an average sensitivity and specificity of 48.47% and 79.38%, respectively. These findings may be useful for guiding decision-making within the perioperative period and may serve to identify patients at increased risk for a prolonged LOS.

11.
Urology ; 189: 1-8, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38777190

RESUMO

OBJECTIVE: To perform a systematic review of the characteristics and outcomes of conscious sedation and local anesthesia for various urologic procedures. Urologic care has much to gain from the routine integration of ambulatory surgery via loco-sedative anesthetic techniques for both surgeon and patient. METHODS: A comprehensive systematic literature search was conducted on PubMed, and Scopus databases following PRISMA criteria from June to August 2021. Articles were included if they were English, prospective, randomized, or nonrandomized controlled trials that used local anesthetic or conscious sedation for urologic interventions in adult patients. Additionally, included studies provided primary data on the use loco-sedative anesthesia and the efficacy and complications. All studies included were further reviewed to assess the biases and conflicts of interests. RESULTS: Thirty-two studies with 6897 patients were included in the review. Mean patient age was 46.4years. The most common anesthetic and analgesic relief was the use of local anesthetic with 1% lidocaine. The majority used lidocaine as an injection, whereas the second most common route of administration was a topical cream. However, there was significant heterogeneity in the type of local or conscious sedation method and whether a combination was used. 44.4% of the studies used the visual analog scale as their primary endpoint. All the studies reported an 83%-100% successful procedure rate without note of significant sedation-related complications. CONCLUSION: Given the high efficacy rates, loco-sedative anesthesia is a promising technique for urologic interventions and should be further investigated to determine whether it may become be the standard of care.


Assuntos
Anestesia Local , Anestésicos Locais , Sedação Consciente , Procedimentos Cirúrgicos Urológicos , Humanos , Anestesia Local/métodos , Procedimentos Cirúrgicos Urológicos/métodos , Sedação Consciente/métodos , Anestésicos Locais/administração & dosagem , Lidocaína/administração & dosagem
12.
Blood Cancer J ; 14(1): 88, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821925

RESUMO

B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25-0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31-3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05-3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21-0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17-0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients.


Assuntos
Antígeno de Maturação de Linfócitos B , Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Antígeno de Maturação de Linfócitos B/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Imunoterapia Adotiva/efeitos adversos , Adulto , Infecções/etiologia , Infecções/epidemiologia , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/efeitos adversos , Idoso de 80 Anos ou mais , Incidência , Imunoconjugados/uso terapêutico , Imunoconjugados/efeitos adversos
13.
Bull Environ Contam Toxicol ; 112(5): 74, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733375

RESUMO

Polycyclic aromatic hydrocarbons (PAHs), dust, and wax were measured in pine needles, and PAHs were also measured in surface soil. Pearson correlation analysis was performed between the analytical values. The main compounds responsible for the increase in total PAHs were non-carcinogenic phenanthrene and fluoranthene. Therefore, the % content of carcinogenic PAHs decreased with a slope = -0.037 (r = 0.47, p < 0.01), as the total PAH concentration in pine needles increased. Correlations between individual PAHs in pine needles and surface soil were very high when only low-number ring PAHs (2R- and 3R-PAHs) were statistically analyzed and significant when only high-number ring PAHs were statistically analyzed. Low-number ring PAH mainly moves in the gas phase and diffuses into the wax layer, so it was found to be statistically significant with the wax content of pine needles. High-number ring PAHs showed a high correlation with the amount of dust in pine needles because they mainly attached to dust particles and accumulated on the surface of pine needles. The ratios of fluoranthene/pyrene and methylphenanthrene/phenanthrene for predicting the origin of atmospheric PAHs have also been proven valid for pine needles.


Assuntos
Monitoramento Ambiental , Pinus , Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/análise , Pinus/química , República da Coreia , Folhas de Planta/química , Fenantrenos/análise , Poluentes do Solo/análise , Poluentes Atmosféricos/análise
14.
Blood ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728378

RESUMO

B-cell maturation antigen (BCMA)-targeting therapeutics have dramatically improved outcomes in relapsed/refractory multiple myeloma (RRMM). However, whether the mechanisms of resistance between these therapies are shared and how the identification of such mechanisms before therapy initiation could refine clinical decision-making remains undefined. We analyzed outcomes for 72 RRMM patients treated with teclistamab, a CD3 x BCMA bispecific antibody (BsAb), 42% (30/72) of whom had prior BCMA-directed therapy exposure. Malignant plasma cell BCMA expression was present in all BCMA therapy-naïve patients. Prior therapy-mediated loss of plasma cell BCMA expression before teclistamab treatment, measured by immunohistochemistry, was observed in 3 patients, none of whom responded to teclistamab, and one of whom also did not respond to ciltacabtagene autoleucel. Whole exome sequencing of tumor DNA from one patient revealed biallelic loss of TNFRSF17 following treatment with belantamab mafodotin. Low-to-undetectable peripheral blood soluble BCMA levels correlated with the absence of BCMA expression by bone marrow plasma cells. Thus, although rare, loss of BCMA expression following TNFRSF17 gene deletions can occur following any BCMA-directed therapy and prevents response to subsequent anti-BCMA-directed treatments, underscoring the importance of verifying the presence of a target antigen.

15.
Blood Cancer J ; 14(1): 84, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802346

RESUMO

Despite being the mainstay of management for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), there is limited data regarding the impact of tocilizumab (TCZ) and corticosteroids (CCS) on chimeric antigen receptor (CAR) T-cell efficacy in multiple myeloma (MM). The present study aims to evaluate the prognostic impact of these immunosuppressants in recipients of BCMA- or GPRC5D-directed CAR T cells for relapsed/refractory MM. Our retrospective cohort involved patients treated with commercial or investigational autologous CAR T-cell products at a single institution from March 2017-March 2023. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), complete response rate (CRR), and overall survival (OS). In total, 101 patients (91% treated with anti-BCMA CAR T cells and 9% treated with anti-GPRC5D CAR T cells) were analyzed. Within 30 days post-infusion, 34% received CCS and 49% received TCZ for CRS/ICANS management. At a median follow-up of 27.4 months, no significant difference in PFS was observed between CCS and non-CCS groups (log-rank p = 0.35) or between TCZ and non-TCZ groups (log-rank p = 0.69). ORR, CRR, and OS were also comparable between evaluated groups. In our multivariable model, administering CCS with/without TCZ for CRS/ICANS management did not independently influence PFS (HR, 0.74; 95% CI, 0.36-1.51). These findings suggest that, among patients with relapsed/refractory MM, the timely and appropriate use of CCS or TCZ for mitigating immune-mediated toxicities does not appear to impact the antitumor activity and long-term outcomes of CAR T-cell therapy.


Assuntos
Corticosteroides , Anticorpos Monoclonais Humanizados , Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Estudos Retrospectivos , Prognóstico , Corticosteroides/uso terapêutico , Adulto , Receptores de Antígenos Quiméricos/uso terapêutico , Idoso de 80 Anos ou mais
16.
Blood Adv ; 8(12): 3246-3253, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38621239

RESUMO

ABSTRACT: Outcomes for patients with relapsed/refractory multiple myeloma (R/RMM) have dramatically improved after the development and now growing utilization of B-cell maturation antigen-targeted chimeric antigen receptor (CAR) T-cell therapy and bispecific antibody (BsAb) therapy. However, health care utilization as a quality-of-life metric in these growing populations has not been thoroughly evaluated. We performed a retrospective cohort study evaluating the frequency and cause of unscheduled health care interactions (UHIs) among patients with R/RMM responding to B-cell maturation antigen-targeted BsAb and CAR T-cell therapies (N = 46). This included the analysis of remote UHIs including calls to physicians' offices and messages sent through an online patient portal. Our results showed that nearly all patients with R/RMM (89%) receiving these therapies required a UHI during the first 125 days of treatment, with a mean of 3.7 UHIs per patient. Patients with R/RMM responding to BsAbs were significantly more likely to remotely contact their physicians' offices (1.8-fold increase; P = .038) or visit an urgent care center (more than threefold increase; P = .012) than patients with R/RMM responding to CAR T-cell therapies. This was largely due to increased reports of mild upper respiratory tract infections in BsAb patients. Our results underscore the need to develop preemptive management strategies for commonly reported symptoms that patients with R/RMM experience while receiving CAR T-cell or BsAb therapies. This preemptive management may significantly reduce unnecessary health care utilization in this vulnerable patient population.


Assuntos
Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Masculino , Imunoterapia Adotiva/métodos , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Idoso , Anticorpos Biespecíficos/uso terapêutico , Adulto , Receptores de Antígenos Quiméricos/uso terapêutico , Qualidade de Vida
17.
Vet Res ; 55(1): 51, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622639

RESUMO

Lyophilized Streptococcus spp. isolates (n = 50) from animal samples submitted to the diagnostic laboratory at the University of Connecticut in the 1940s were revivified to investigate the genetic characteristics using whole-genome sequencing (WGS). The Streptococcus spp. isolates were identified as follows; S. agalactiae (n = 14), S. dysgalactiae subsp. dysgalactiae (n = 10), S. dysgalactiae subsp. equisimils (n = 5), S. uberis (n = 8), S. pyogenes (n = 7), S. equi subsp. zooepidemicus (n = 4), S. oralis (n = 1), and S. pseudoporcinus (n = 1). We identified sequence types (ST) of S. agalactiae, S. dysgalactiae, S. uberis, S. pyogenes, and S. equi subsp. zooepidemicus and reported ten novel sequence types of those species. WGS analysis revealed that none of Streptococcus spp. carried antibiotic resistance genes. However, tetracycline resistance was observed in four out of 15 S. dysgalactiae isolates and in one out of four S. equi subsp. zooepidemicus isolate. This data highlights that antimicrobial resistance is pre-existed in nature before the use of antibiotics. The draft genome sequences of isolates from this study and 426 complete genome sequences of Streptococcus spp. downloaded from BV-BRC and NCBI GenBank database were analyzed for virulence gene profiles and phylogenetic relationships. Different Streptococcus species demonstrated distinct virulence gene profiles, with no time-related variations observed. Phylogenetic analysis revealed high genetic diversity of Streptococcus spp. isolates from the 1940s, and no clear spatio-temporal clustering patterns were observed among Streptococcus spp. analyzed in this study. This study provides an invaluable resource for studying the evolutionary aspects of antibiotic resistance acquisition and virulence in Streptococcus spp.


Assuntos
Antibacterianos , Infecções Estreptocócicas , Animais , Antibacterianos/farmacologia , Virulência/genética , Infecções Estreptocócicas/veterinária , Filogenia , Streptococcus/genética
18.
Blood Adv ; 8(12): 3038-3044, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38598713

RESUMO

ABSTRACT: Teclistamab (Tec) is a first-in-class BCMA × CD3 bispecific T-cell engager antibody approved for treating multiple myeloma progressing after at least 4 lines of therapy. The objective of this study was to evaluate the rate of cytokine release syndrome (CRS) in patients who were treated with commercial Tec and had prior exposure to other T-cell redirection therapies. A retrospective chart review was performed to identify patients who completed the Tec step-up dosing phase between November 2022 and November 2023. Patients were divided into 2 cohorts based on prior exposure to T-cell redirection therapy (cohort 1: T-cell redirection therapy experienced; cohort 2: T-cell redirection therapy naïve). The primary objective was to compare the differences in the rates of CRS between the 2 cohorts. Univariate and multivariate logistic regression analyses were performed to assess the association between CRS rates with Tec and prior treatment with T-cell redirection therapy. A total of 72 patients were included in the analysis (27 in cohort 1 and 45 in cohort 2). The CRS rates were significantly lower in cohort 1 (37%, n = 10) compared with cohort 2 (80%, n = 36; P = .0004). Based on multivariate logistic regression analysis, patients without prior exposure to T-cell redirection therapy (cohort 2) had about a fourfold increase in the incidence of CRS (95% confidence interval, 1.40-14.90; P = .0002) with Tec. In our study, prior exposure to T-cell redirection therapy reduced the risk of CRS with Tec during the step-up dosing phase. This observation will allow for the optimization of CRS prophylactic strategies for Tec.


Assuntos
Síndrome da Liberação de Citocina , Mieloma Múltiplo , Linfócitos T , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Síndrome da Liberação de Citocina/etiologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Estudos Retrospectivos , Idoso , Anticorpos Biespecíficos/uso terapêutico , Antígeno de Maturação de Linfócitos B/antagonistas & inibidores
19.
Environ Pollut ; 350: 124001, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38642793

RESUMO

In the southeast and east coasts of the Republic of Korea, it is essential to monitor mercury accumulation in coastal organisms in view of the higher mercury distribution in sediments and human samples. However, mercury pollution monitoring in organisms, especially higher trophic-level organisms that can exhibit high mercury accumulation, is limited. Here, we examined the applicability of the eggs of the black-tailed gull (Larus crassirostris), which belongs to a high trophic level, for mercury monitoring in coastal areas. Breeding sites were selected in West, Southeast, and East Seas with different mercury concentrations in other matrices (sediment and biological samples of residents). The 5-year mean total mercury concentration in eggs collected during the breeding seasons from 2016 to 2020 was lower in Baengnyeongdo (705 ± 81 ng/g dry weight (dry), West Sea) than in Hongdo (1,207 ± 214 ng/g dry, Southeast Sea) and Ulleungdo (1,095 ± 95 ng/g dry, East Sea). The different patterns of mercury concentration in gull eggs among the breeding sites was consistent with those in the other matrices among the coastal areas. These results support the applicability of the black-tailed gull egg as an indicator for establishing a monitoring framework in the coastal areas of the Republic of Korea.


Assuntos
Charadriiformes , Monitoramento Ambiental , Mercúrio , Óvulo , Mercúrio/análise , República da Coreia , Charadriiformes/metabolismo , Monitoramento Ambiental/métodos , Animais , Óvulo/química , Poluentes Químicos da Água/análise , Poluentes Ambientais/análise
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