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4.
J Surg Oncol ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39315466

RESUMEN

BACKGROUND: Lymphatic drainage from the arm may be altered after axillary lymph node dissection (ALND). Understanding these alterations is important as they may change standard surgical and radiation treatment in recurrent breast cancer or upper extremity skin cancers, including melanoma. METHODS: Utilizing a single-institution planar and single photon emission computed tomography/computed tomography lymphoscintigraphy database, we identified patients with a diagnosis of upper extremity cutaneous melanoma from 2008 to 2023 who previously underwent ALND for cancer treatment and did not develop upper extremity cancer-related lymphedema. ALND patients were matched to control patients presenting with cutaneous melanomas at the same anatomic sites. Sentinel lymph nodes (SLNs) were compared between both groups. RESULTS: Of 3628 upper extremity melanoma cutaneous patients, 934 met inclusion criteria, including 22 ALND and 912 control patients. Level I axillary SLN drainage was observed in 98% of controls and 27% of ALND patients (p < 0.001). Level II axillary SLN drainage was observed in 3% of controls and 27% of ALND patients (p < 0.001). Level III axillary SLN drainage was observed in 1% of controls and 32% of ALND patients (p < 0.001). Epitrochlear SLN drainage was observed in 9% of controls and 32% of ALND patients, respectively (p < 0.046). Brachial SLN drainage was observed in 4% of controls and 23% of ALND patients (p < 0.001). CONCLUSIONS: Distinct changes in functional lymphatic drainage were seen between the arms of patients who previously underwent ALND versus control patients. Levels II and III axillary, epitrochlear, and brachial nodes are possible sites of metastatic disease that should be considered in patients with a prior ALND.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39277550

RESUMEN

PURPOSE: Sentinel node biopsy (SNB) is a common staging tool for breast cancer. Initially, peritumoral (PT) injections were used, however subareolar (SA) injections were later introduced to simplify the technique. Controversy remains regarding whether PT and SA injections map the same sentinel lymph nodes (SLNs). This study aimed to determine whether the regional location of breast SLNs differs when using PT versus SA injections using a large dataset from a single institution. METHODS: A total of 1035 patients who underwent breast SNB (PT injections: n = 858 and SA injections: n = 177) with lymphoscintigraphy and SPECT/CT were included. The identified SLN locations using SA injections were compared with those using PT injections. Differences in drainage proportions and odds ratios (ORs) for each clockface breast region and the whole breast were calculated using a two-proportion z-test and Fisher's Exact Test. RESULTS: A higher proportion of internal mammary SLNs were identified using PT injections for the whole breast (0.30 versus 0.09) and for all breast regions, with all regions showing statistical significance except the upper outer quadrant. Similarly, ORs showed identification of internal mammary SLNs was significantly higher when using PT injections (4.35, 95% CI 2.53 to 7.95). There were no significant differences in identifying axillary SLNs between injection sites. CONCLUSION: This is the largest cohort study to compare the regional location of breast SLNs identified using PT injections versus SA injections. Discordance was shown in the SLNs identified between injection techniques, with PT injections more frequently identifying internal mammary SLNs.

6.
Science ; 385(6709): eadp2065, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39116219

RESUMEN

Hematopoietic stem cells (HSCs) are routinely mobilized from the bone marrow (BM) to the blood circulation for clinical transplantation. However, the precise mechanisms by which individual stem cells exit the marrow are not understood. This study identified cell-extrinsic and molecular determinants of a mobilizable pool of blood-forming stem cells. We found that a subset of HSCs displays macrophage-associated markers on their cell surface. Although fully functional, these HSCs are selectively niche-retained as opposed to stem cells lacking macrophage markers, which exit the BM upon forced mobilization. Macrophage markers on HSCs could be acquired through direct transfer by trogocytosis, regulated by receptor tyrosine-protein kinase C-Kit (CD117), from BM-resident macrophages in mouse and human settings. Our study provides proof of concept that adult stem cells utilize trogocytosis to rapidly establish and activate function-modulating molecular mechanisms.


Asunto(s)
Movilización de Célula Madre Hematopoyética , Células Madre Hematopoyéticas , Proteínas Proto-Oncogénicas c-kit , Trogocitosis , Animales , Humanos , Ratones , Células Madre Adultas/fisiología , Movilización de Célula Madre Hematopoyética/métodos , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/fisiología , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-kit/metabolismo , Proteínas Proto-Oncogénicas c-kit/genética , Nicho de Células Madre , Lectina 1 Similar a Ig de Unión al Ácido Siálico/metabolismo , Antígenos de Diferenciación
7.
J Surg Oncol ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138920

RESUMEN

BACKGROUND: Variations of hand and forearm lymphatic drainage to upper-arm lymphatic pathways may impact the route of melanoma metastasis. This study compared rates of lymphatic drainage to epitrochlear nodes between anatomic divisions of the hand and forearm to determine whether the anatomic distribution of hand and forearm melanomas affects the likelihood of drainage to epitrochlear lymph nodes. METHODS: Using a single-institution lymphoscintigraphy database, we identified all patients with cutaneous melanoma on the hand and forearm. A body-map two-dimensional coordinate system was used to classify cutaneous melanoma sites between radial-ulnar and dorsal-volar divisions. Sentinel lymph nodes (SLNs) visualized on lymphoscintigraphy were recorded. Proportions of patients with epitrochlear SLNs were compared between anatomic divisions using χ2 analysis. RESULTS: Of 3628 upper extremity cutaneous melanoma patients who underwent lymphatic mapping with lymphoscintigraphy, 1400 met inclusion criteria. Twenty-one percent of patients demonstrated epitrochlear SLNs. Epitrochlear SLNs were observed in 27% of dorsal forearm melanomas and 15% of volar forearm melanomas (p < 0.001). Epitrochlear SLNs were observed in 31% of ulnar forearm melanomas and 17% of radial forearm melanomas (p < 0.001). CONCLUSIONS: Higher proportions of dorsal and ulnar forearm melanomas have epitrochlear SLNs. Metastasis to epitrochlear SLNs may be more likely from melanomas in these respective forearm regions.

8.
Urology ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39208947

RESUMEN

OBJECTIVE: To prospectively assess surgical outcomes, complications, and patient-reported tolerability of invasive scrotal surgeries under local anesthesia (LA) alone, without sedation, compared to tolerability of penile procedures commonly performed in this manner. METHODS: Adult patients undergoing penile and scrotal surgeries under LA only were enrolled from August 2022 to June 2023 (NCT05617261). Demographics, surgeon-perceived and patient-reported pain, and surgical variables were collected. Tolerability to the procedures and future anesthetic choice for a repeat procedure was assessed on follow-up. Complication data were collected, including recurrence, infection, excessive pain, and emergency room and family physician visits. RESULTS: Hundred and seven patients were enrolled with a mean age ± SD of 42.2 ± 16.4 years. There was a 100% procedural success rate and no cases of perioperative complications or escalation of anesthetic. Around 92.4% (n = 97) of patients indicated they would opt for LA only for a hypothetical repeat procedure. Of the minority opting for general anesthetic, most indicated discomfort or preferring an element of amnesia. No differences between intraoperative pain or tolerability scores of invasive scrotal procedures compared to penile procedures were observed. On univariate analysis, longer procedure duration (P = .003), cannabis use (P = .01), and higher intra-operative pain (P = .005) was associated with lower tolerability. CONCLUSION: LA alone in an office-based setting is promising for scrotal surgeries. It offers similarly high patient tolerability compared to procedures that are routinely performed under LA, with the preservation of outcomes. Adopting this method has the potential for substantial cost savings, reduced wait times, enhanced accessibility, and improved surgical efficiency.

9.
Urology ; 192: 6-11, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38972394

RESUMEN

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.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios , Anestesia Local , Anestésicos Locales , Combinación Lidocaína y Prilocaína , Dolor Postoperatorio , Humanos , Masculino , Anestésicos Locales/administración & dosificación , Método Doble Ciego , Anestesia Local/métodos , Procedimientos Quirúrgicos Ambulatorios/métodos , Combinación Lidocaína y Prilocaína/administración & dosificación , Persona de Mediana Edad , Adulto , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/etiología , Dolor Postoperatorio/tratamiento farmacológico , Dimensión del Dolor , Procedimientos Quirúrgicos Urológicos Masculinos/métodos , Lidocaína/administración & dosificación , Prilocaína/administración & dosificación , Resultado del Tratamiento , Escroto/cirugía
10.
Cancer Imaging ; 24(1): 97, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080795

RESUMEN

BACKGROUND: The identification and assessment of sentinel lymph nodes (SLNs) in breast cancer is important for optimised patient management. The aim of this study was to develop an interactive 3D breast SLN atlas and to perform statistical analyses of lymphatic drainage patterns and tumour prevalence. METHODS: A total of 861 early-stage breast cancer patients who underwent preoperative lymphoscintigraphy and SPECT/CT were included. Lymphatic drainage and tumour prevalence statistics were computed using Bayesian inference, non-parametric bootstrapping, and regression techniques. Image registration of SPECT/CT to a reference patient CT was carried out on 350 patients, and SLN positions transformed relative to the reference CT. The reference CT was segmented to visualise bones and muscles, and SLN distributions compared with the European Society for Therapeutic Radiology and Oncology (ESTRO) clinical target volumes (CTVs). The SLN atlas and statistical analyses were integrated into a graphical user interface (GUI). RESULTS: Direct lymphatic drainage to the axilla level I (anterior) node field was most common (77.2%), followed by the internal mammary node field (30.4%). Tumour prevalence was highest in the upper outer breast quadrant (22.9%) followed by the retroareolar region (12.8%). The 3D atlas had 765 SLNs from 335 patients, with 33.3-66.7% of axillary SLNs and 25.4% of internal mammary SLNs covered by ESTRO CTVs. CONCLUSION: The interactive 3D atlas effectively displays breast SLN distribution and statistics for a large patient cohort. The atlas is freely available to download and is a valuable educational resource that could be used in future to guide treatment.


Asunto(s)
Neoplasias de la Mama , Imagenología Tridimensional , Ganglio Linfático Centinela , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Ganglio Linfático Centinela/diagnóstico por imagen , Ganglio Linfático Centinela/patología , Persona de Mediana Edad , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , Imagenología Tridimensional/métodos , Anciano , Adulto , Linfocintigrafia/métodos , Biopsia del Ganglio Linfático Centinela/métodos , Anciano de 80 o más Años , Metástasis Linfática/diagnóstico por imagen
11.
Can Urol Assoc J ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39037505

RESUMEN

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.

12.
Can Urol Assoc J ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39037507

RESUMEN

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.

13.
Res Sq ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38883739

RESUMEN

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.

14.
Can Urol Assoc J ; 18(10): 335-340, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38896478

RESUMEN

INTRODUCTION: We aimed to investigate the surgical outcomes following inguinal and subinguinal urologic 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 the spermatic cord (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 similarly 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 the unnecessary risks of general or spinal anesthesia, representing an opportunity to transfer these cases outside of hospitals' operating rooms into outpatient ambulatory centers.

15.
Clin Nucl Med ; 49(9): e451-e452, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38861407

RESUMEN

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 68 Ga-DOTATATE PET/CT demonstrated intense tracer avidity within the pancreatic lesion with minimal uptake in the adrenal lesions. Conversely, a 123 I-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.


Asunto(s)
3-Yodobencilguanidina , Neoplasias de las Glándulas Suprarrenales , Compuestos Organometálicos , Feocromocitoma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Enfermedad de von Hippel-Lindau , Humanos , Feocromocitoma/diagnóstico por imagen , Adolescente , Masculino , Enfermedad de von Hippel-Lindau/diagnóstico por imagen , Enfermedad de von Hippel-Lindau/complicaciones , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen
16.
Bull Environ Contam Toxicol ; 112(5): 74, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38733375

RESUMEN

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.


Asunto(s)
Monitoreo del Ambiente , Pinus , Hidrocarburos Policíclicos Aromáticos , Hidrocarburos Policíclicos Aromáticos/análisis , Pinus/química , República de Corea , Hojas de la Planta/química , Fenantrenos/análisis , Contaminantes del Suelo/análisis , Contaminantes Atmosféricos/análisis
17.
Blood Cancer J ; 14(1): 84, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802346

RESUMEN

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.


Asunto(s)
Corticoesteroides , Anticuerpos Monoclonales Humanizados , Inmunoterapia Adoptiva , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anciano , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Estudios Retrospectivos , Pronóstico , Corticoesteroides/uso terapéutico , Adulto , Receptores Quiméricos de Antígenos/uso terapéutico , Anciano de 80 o más Años
18.
Blood Cancer J ; 14(1): 88, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38821925

RESUMEN

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.


Asunto(s)
Antígeno de Maduración de Linfocitos B , Inmunoterapia Adoptiva , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Antígeno de Maduración de Linfocitos B/inmunología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Inmunoterapia Adoptiva/efectos adversos , Adulto , Infecciones/etiología , Infecciones/epidemiología , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/efectos adversos , Anciano de 80 o más Años , Incidencia , Inmunoconjugados/uso terapéutico , Inmunoconjugados/efectos adversos
19.
Urology ; 189: 1-8, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38777190

RESUMEN

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.


Asunto(s)
Anestesia Local , Anestésicos Locales , Sedación Consciente , Procedimientos Quirúrgicos Urológicos , Humanos , Anestesia Local/métodos , Procedimientos Quirúrgicos Urológicos/métodos , Sedación Consciente/métodos , Anestésicos Locales/administración & dosificación , Lidocaína/administración & dosificación
20.
Blood ; 144(4): 402-407, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38728378

RESUMEN

ABSTRACT: 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 × BCMA bispecific antibody, 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 1 of whom also did not respond to ciltacabtagene autoleucel. Whole exome sequencing of tumor DNA from 1 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.


Asunto(s)
Antígeno de Maduración de Linfocitos B , Resistencia a Antineoplásicos , Mieloma Múltiple , Humanos , Mieloma Múltiple/inmunología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , Antígeno de Maduración de Linfocitos B/genética , Antígeno de Maduración de Linfocitos B/inmunología , Masculino , Femenino , Persona de Mediana Edad , Anticuerpos Biespecíficos/uso terapéutico , Anciano , Anticuerpos Monoclonales Humanizados
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