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BACKGROUND: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-LPD) is an increasingly recognized entity with heterogeneous management strategies that may include radiotherapy. OBJECTIVE: Our aim was to characterize treatment options for PCSM-LPD, with a focus on the role of radiotherapy. METHODS: This is a retrospective review of 46 patients seen in the Cutaneous Lymphoma Program at the University of Texas MD Anderson Cancer Center, with a clinicopathologic review consistent with PCSM-LPD. All patients were biopsied and underwent observation, topical/intralesional steroids, and/or radiotherapy. Patients were confirmed to have residual disease prior to radiotherapy. RESULTS: All patients achieved a complete response (CR). Sixteen patients (35%) received focal radiotherapy, with a CR in 15 (94%). The CR rate following ultra-low-dose radiotherapy (4 Gy in 1-2 fractions) was 92%. There was no grade 3 toxicity after radiotherapy. Thirty patients were managed without radiotherapy, with excision and observation or steroids. CONCLUSION: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder has excellent outcomes, and management strategies may include observation following biopsy, steroids, or radiation. Ultra-low-dose radiotherapy results in excellent outcomes with limited toxicity and is effective for persistent lesions after steroidal therapy.
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Importance: Radiation therapy to doses of 24 to 36 Gy is currently used to treat indolent B-cell lymphoma of the ocular adnexa; however, ocular adverse effects are common. Objective: To determine if a response-adapted radiation therapy strategy will result in excellent disease outcomes while reducing orbital morbidity. Design, Setting, and Participants: This single-institution, phase 2 prospective nonrandomized controlled trial of a response-adapted strategy involved 50 evaluable patients with stage I to IV indolent B-cell lymphoma of the ocular adnexa enrolled between July 2015 and January 2021. This treatment approach was also retrospectively evaluated with a separate 55-patient cohort treated between March 2013 and October 2021. All data were analyzed between November 2021 and December 2023. Interventions: Patients were treated with ultralow-dose radiation therapy to 4 Gy in 2 fractions and assessed for response at 3-month intervals. Patients with persistent orbital lymphoma were offered an additional 20 Gy in 10 fractions to complete the response-adapted treatment. Main Outcome and Measures: The primary end point was 2-year local orbital control within the irradiated field after response-adapted therapy. Secondary end points included overall survival and complete response rate. Results: The 50 prospective patients were a median (range) of 63 (29-88) years old, and 31 (62%) were female. Among the 50 patients, 32 (64%) had mucosa-associated lymphoid tissue lymphoma, 12 (24%) had follicular lymphoma, and 6 (12%) had unclassifiable low-grade B-cell lymphoma. Thirty-one patients (62%) had stage I disease, and 36 (72%) were newly diagnosed. At a median follow-up of 37.4 (95% CI, 33.7-52.5) months, the 2-year local control rate was 89.4% (95% CI, 81.0%-98.7%), and the 2-year overall survival rate was 98.0% (95% CI, 94.1%-100%); 45 patients (90.0%; 95% CI, 78.2%-96.7%) experienced a complete response to response-adapted radiation, including 44 patients with a complete response to ultralow-dose radiation and 1 patient with a complete response after an additional 20 Gy. No local recurrences were observed among patients with a complete response to response-adapted therapy. No grade 3 or higher toxic effects were observed. In a planned subset analysis of 22 patients with newly diagnosed, untreated stage I mucosa-associated lymphoid tissue lymphoma, the 2-year local control rate was 90.7% (95% CI, 79.2%-100%), and the 2-year freedom from distant relapse rate was 95.2% (95% CI, 86.6%-100%). Conclusion and Relevance: In this nonrandomized controlled trial, response-adapted ultralow-dose therapy for indolent orbital B-cell lymphoma resulted in reduced radiation exposure, negligible toxic effects, and excellent disease outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02494700.
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BACKGROUND: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach. METHODS: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Patients with a complete response to 4 Gy via endoscopy and imaging at 3-4 months were observed; patients with a partial response were re-evaluated in 6-9 months. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. The primary endpoint was gastric complete response at 1 year (second evaluation timepoint) after 4 Gy treatment. All analyses were performed as intention to treat. This trial is registered at ClinicalTrials.gov (NCT03680586) and is complete and closed to enrolment. FINDINGS: Between March 27, 2019, and Oct 12, 2021, we enrolled 24 eligible patients. The median age of participants was 67 years (IQR 58-74; range 40-85); 15 (63%) were female and nine (37%) male; 18 (75%) were White, four (17%) Asian, and two (8%) Hispanic; 20 (83%) had stage I disease, one (4%) stage II, and three (13%) stage IV. Median follow-up time was 36 months (IQR 26-42). 20 patients (83%) had a complete response to 4 Gy (16 at 3-4 months, four at 9-13 months); two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months; all had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths. INTERPRETATION: Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months. This response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity. FUNDING: National Cancer Institute.
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Linfoma de Células B de la Zona Marginal , Dosificación Radioterapéutica , Neoplasias Gástricas , Humanos , Linfoma de Células B de la Zona Marginal/radioterapia , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Gástricas/radioterapia , Neoplasias Gástricas/patología , Anciano , Proyectos Piloto , Adulto , Estudios Prospectivos , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
Primary human hepatocyte (PHH) transplantation is a promising alternative to liver transplantation, whereby liver function could be restored by partial repopulation of the diseased organ with healthy cells. However, currently PHH engraftment efficiency is low and benefits are not maintained long-term. Here we refine two male mouse models of human chronic and acute liver diseases to recapitulate compromised hepatocyte proliferation observed in nearly all human liver diseases by overexpression of p21 in hepatocytes. In these clinically relevant contexts, we demonstrate that transient, yet robust expression of human hepatocyte growth factor and epidermal growth factor in the liver via nucleoside-modified mRNA in lipid nanoparticles, whose safety was validated with mRNA-based COVID-19 vaccines, drastically improves PHH engraftment, reduces disease burden, and improves overall liver function. This strategy may overcome the critical barriers to clinical translation of cell therapies with primary or stem cell-derived hepatocytes for the treatment of liver diseases.
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Factor de Crecimiento de Hepatocito , Hepatocitos , Nanopartículas , ARN Mensajero , Animales , Hepatocitos/metabolismo , Hepatocitos/trasplante , Humanos , Ratones , Masculino , ARN Mensajero/metabolismo , ARN Mensajero/genética , Nanopartículas/química , Factor de Crecimiento de Hepatocito/metabolismo , Factor de Crecimiento de Hepatocito/genética , Modelos Animales de Enfermedad , Hígado/metabolismo , Factor de Crecimiento Epidérmico/metabolismo , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , COVID-19/terapia , Hepatopatías/terapia , Hepatopatías/metabolismo , Hepatopatías/genética , Proliferación Celular , SARS-CoV-2/genética , LiposomasRESUMEN
Beginning in 2023, we observed increased Plasmodium vivax malaria cases at an institution in Los Angeles, California, USA. Most cases were among migrants from China who traveled to the United States through South and Central America. US clinicians should be aware of possible P. vivax malaria among immigrants from China.
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Emigrantes e Inmigrantes , Malaria Vivax , Plasmodium vivax , Viaje , Humanos , Malaria Vivax/epidemiología , Malaria Vivax/parasitología , China/epidemiología , Estados Unidos/epidemiología , Masculino , Adulto , Femenino , Persona de Mediana Edad , Adulto JovenRESUMEN
Though testing for infectious diseases has long been performed in traditional clincial laboratory settings, more widespread availability of waived testing is expanding accessibility of patients to rapid test results. This is being further expanded to home testing. Nevertheless, with this greater democratization and availability of clinical testing there are important limitations that need to be balanced. In this article, we review the current test landscape for infectious diseases waived testing and opportunities for assuring optimal quality testing.
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Enfermedades Transmisibles , Laboratorios Clínicos , Humanos , Técnicas de Laboratorio Clínico , Enfermedades Transmisibles/diagnóstico , LaboratoriosRESUMEN
Primary human hepatocyte (PHH) transplantation is a promising alternative to liver transplantation, whereby liver function could be restored by partial repopulation of the diseased organ with healthy cells. However, currently PHH engraftment efficiency is low and benefits are not maintained long-term. Here we refine two mouse models of human chronic and acute liver diseases to recapitulate compromised hepatocyte proliferation observed in nearly all human liver diseases by overexpression of p21 in hepatocytes. In these clinically relevant contexts, we demonstrate that transient, yet robust expression of human hepatocyte growth factor and epidermal growth factor in the liver via nucleoside-modified mRNA in lipid nanoparticles, whose safety was validated with mRNA-based COVID-19 vaccines, drastically improves PHH engraftment, reduces disease burden, and improves overall liver function. This novel strategy may overcome the critical barriers to clinical translation of cell therapies with primary or stem cell-derived hepatocytes for the treatment of liver diseases.
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PURPOSE: Radiation therapy (RT) is the standard treatment for solitary plasmacytoma (SP); however, the optimal management of RT-refractory SPs is unknown. We examined outcomes after early systemic therapy, surgical resection, or observation for patients with RT-refractory disease and assessed the potential impact of treatment selection on disease outcomes. METHODS AND MATERIALS: We retrospectively reviewed patients with SP treated with definitive radiation and evaluated at a single institution with persistent disease on imaging or biopsy. Descriptive statistics were used to characterize patient and disease characteristics and treatment outcomes. RESULTS: Of 102 total SP patients, 17 (17%) were RT-refractory. The median RT dose was 45 Gy, and median follow-up was 71 months from end of RT. Fifteen patients had additional treatment for refractory disease at a median time of 9.5 months after RT, with the following subsequent interventions: surgical resection (n = 4), additional RT (n = 2), systemic therapy without evidence of multiple myeloma (MM; n = 4), systemic therapy for progression to MM (n = 5), and observation (n = 2). Of 4 patients treated with surgical resection, 3 progressed to MM 22 to 43 months after diagnosis. Of 2 patients treated with additional RT, neither responded, and both had pathologic confirmation of residual disease after the second course. Four patients treated with systemic therapy without MM all had complete responses on positron emission tomography and no subsequent MM progression. Eight patients were initially observed after RT for ≥12 months (n = 8) or ≥24 months (n = 6). Of the 2 patients in continued observation, both had stable/unchanged avidity after radiation treatment for 12 and 22 months and ultimately had a slow decrease of disease avidity over multiple years. CONCLUSIONS: Patients with RT-refractory SPs can achieve good local control with alternative therapies, such as surgery or systemic therapy, if needed. Additional RT does not seem to be effective. Given the known high rates of progression from SP to MM, close observation of asymptomatic persistent disease until disease progression is likely sufficient in most cases.
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Neoplasias Óseas , Mieloma Múltiple , Plasmacitoma , Humanos , Plasmacitoma/patología , Estudios Retrospectivos , Mieloma Múltiple/diagnóstico , Resultado del Tratamiento , Neoplasias Óseas/radioterapia , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: Individuals with cystic fibrosis (CF) often have psychological difficulties on top of their medically complex care, such as anxiety, depression, and medical mistrust. These have been shown to be associated with worse adherence, pulmonary function test results, and other health outcomes. In this pilot trial, we implemented a journaling program based on narrative therapy methodology to improve mental and physical health outcomes for individuals with CF. METHODS: Eight adolescents aged 12-17 with a confirmed diagnosis of CF followed in a single center CF clinic were emailed weekly journaling prompts that explored topics like treatment adherence, feeling different with CF, anxiety, depression, and interpersonal relationships. Subjects completed surveys about their experience with the writing assignment and measures of wellness including the Pediatric Symptom Checklist (PSC-17) and baseline health data was collected from the electronic medical records. RESULTS: The average score for the PSC-17 decreased by 5.5 points, and fell to less than 28 (mean 23.5, SD 12.2), which is the cutoff for screening positive for behavioral or emotional problems. Participants reported the study was enjoyable and had improvement in feelings of anxiety/depression. 100% of participants responded "Strongly Agree" to the statement "I recommend other people with CF to write about the topics from this study." CONCLUSIONS: The journaling intervention for individuals with CF was feasible and well received. Initial results show improvement in PSC-17 and other well-being measures. Further studies are needed to evaluate the impact of journaling on mental health and disease outcomes.
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Fibrosis Quística , Humanos , Adolescente , Niño , Confianza , Depresión/etiología , Ansiedad/etiología , Salud Mental , Calidad de VidaRESUMEN
Classic Hodgkin lymphoma (HL) is rare disease, with an incidence of approximately 85,000 patients globally per year and a predilection for adolescents and young adults (ages 15-39). Since the introduction of combination chemotherapy in the 1960's and radiation dating back to the early 1900's, therapeutic options and by extension, clinical outcomes have improved dramatically with 5-year overall survival (OS) approaching 90% today. [1](#ref-0001) Advances in understanding HL biology have additionally facilitated development of targeted agents and immunotherapy which have further improved short and long-term outcomes. Despite continued improvements in up-front and salvage therapy, long-term survivors of HL experience several treatment-associated late toxicities, thus, along with efforts to improve therapeutic efficacy, efforts to reduce late effects remain a high-priority in the field.
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The liver is known for its remarkable regenerative ability through proliferation of hepatocytes. Yet, during chronic injury or severe hepatocyte death, proliferation of hepatocytes is exhausted. To overcome this hurdle, we propose vascular-endothelial-growth-factor A (VEGFA) as a therapeutic means to accelerate biliary epithelial-cell (BEC)-to-hepatocyte conversion. Investigation in zebrafish establishes that blocking VEGF receptors abrogates BEC-driven liver repair, while VEGFA overexpression promotes it. Delivery of VEGFA via nonintegrative and safe nucleoside-modified mRNA encapsulated into lipid nanoparticles (mRNA-LNPs) in acutely or chronically injured mouse livers induces robust BEC-to-hepatocyte conversion and elimination of steatosis and fibrosis. In human and murine diseased livers, we further identified VEGFA-receptor KDR-expressing BECs associated with KDR-expressing cell-derived hepatocytes. This work defines KDR-expressing cells, most likely being BECs, as facultative progenitors. This study reveals unexpected therapeutic benefits of VEGFA delivered via nucleoside-modified mRNA-LNP, whose safety is widely validated with COVID-19 vaccines, for harnessing BEC-driven repair to potentially treat liver diseases.
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Hepatopatías , Pez Cebra , Animales , Ratones , Humanos , ARN Mensajero/genética , Vacunas contra la COVID-19 , Nucleósidos , Hepatocitos , Hígado , Células Epiteliales , Hepatopatías/patología , Fibrosis , Regeneración Hepática , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
The bioMérieux BIOFIRE Joint Infection (JI) Panel is a multiplex in vitro diagnostic test for the simultaneous and rapid (~1 h) detection of 39 potential pathogens and antimicrobial resistance (AMR) genes directly from synovial fluid (SF) samples. Thirty-one species or groups of microorganisms are included in the kit, as well as several AMR genes. This study, performed to evaluate the BIOFIRE JI Panel for regulatory clearance, provides data from a multicenter evaluation of 1,544 prospectively collected residual SF samples with performance compared to standard-of-care (SOC) culture for organisms or polymerase chain reaction (PCR) and sequencing for AMR genes. The BIOFIRE JI Panel demonstrated a sensitivity of 90.9% or greater for all but six organisms and a positive percent agreement (PPA) of 100% for all AMR genes. The BIOFIRE JI Panel demonstrated a specificity of 98.5% or greater for detection of all organisms and a negative percent agreement (NPA) of 95.7% or greater for all AMR genes. The BIOFIRE JI Panel provides an improvement over SOC culture, with a substantially shorter time to result for both organisms and AMR genes with excellent sensitivity/PPA and specificity/NPA, and is anticipated to provide timely and actionable diagnostic information for joint infections in a variety of clinical scenarios.
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Antiinfecciosos , Artritis Infecciosa , Humanos , Saccharomyces cerevisiae/genética , Líquido Sinovial/microbiología , Reacción en Cadena de la Polimerasa Multiplex , Bacterias/genética , Artritis Infecciosa/diagnósticoRESUMEN
Primary treatment of multiple myeloma (MM) often involves systemic induction therapy (SIT) followed by autologous stem cell transplantation (ASCT). Radiation therapy (RT) is sometimes used for palliation; however, many practitioners avoid RT out of concern that future peripheral blood progenitor cell (PBPC) collection required for ASCT may be compromised. In this study, we retrospectively examined the possible effect of RT on PBPC collection. We reviewed the charts of 732 patients with MM treated with RT at our institution from 1999 to 2017, including patients who received RT prior to PBPC collection for planned ASCT. RT plans (both MM and non-MM RT) were reviewed to estimate the percentage of bone marrow (BM) treated using published estimates of skeletal BM distribution. Statistics were performed using Pearson correlation and the t-test. The 732 MM patients included 485 planned for ASCT; of these, 223 received RT prior to PBPC collection and were included in the final cohort. The median age at PBPC collection was 59 years (range, 33 to 80 years). For SIT, patients received combination regimens including the following agents: bortezomib (142 patients; 64%), lenalidomide (111 patients; 50%), and alkylators (46 patients; 21%). Nine patients (4%) received dexamethasone alone. The median cumulative %BM treated per patient was 6.7 (range .0 to 47.4). The median RT dose was 24 Gy (range, 10.0 to 75.6 Gy). Mobilization was performed using granulocyte-colony stimulating factor (G-CSF) alone (189 patients; 85%), G-CSF with plerixafor (15 patients; 7%), or chemotherapy (19 patients; 9%). A median of 7.8 × 106 CD34+/kg PBPCs (range, .5 to 54.8× 106 CD34+/kg) were collected in a median of 3 (range, 1 to 9) apheresis procedures. One hundred ninety-six patients (99%) collected ≥2.0 × 106 CD34+/kg PBPCs, and 166 (83%) collected >5.0 × 106 CD34+/kg PBPCs. The number of PBPCs collected was not associated with %BM treated (P = .15) or RT dose (P = .56). The number of apheresis procedures performed was not associated with %BM treated (P = .54) or RT dose (P = .85). The amount of PBPCs collected did not differ significantly between patients receiving RT to the pelvis/sacrum (P = .20) and those receiving RT to the spine (P = .13). The time to platelet engraftment was longer for patients with higher %BM treated (P = .02). Eleven patients did not undergo a confirmed ASCT, owing to patient preference (3 patients), trial therapy (1 patient), comorbidities (1 patient), election for hospice (1 patient), inadequate collection (4 patients), or inadequate follow-up (1 patient). In our study cohort, RT prior to ASCT did not impair successful ASCT. RT must be carefully planned and delivered to ensure safe incorporation into pre-ASCT treatment regimens.
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Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Mieloma Múltiple , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Mieloma Múltiple/radioterapia , Movilización de Célula Madre Hematopoyética , Estudios Retrospectivos , Trasplante Autólogo , Antígenos CD34 , Factor Estimulante de Colonias de Granulocitos/uso terapéuticoRESUMEN
The use of clinical molecular diagnostic methods for detecting microbial pathogens continues to expand and, in some cases, supplant conventional identification methods in various scenarios. Analytical and clinical benefits of multiplex molecular panels for the detection of respiratory pathogens have been demonstrated in various studies. The use of these panels in managing different patient populations has been incorporated into clinical guidance documents. The Association for Molecular Pathology's Infectious Diseases Multiplex Working Group conducted a review of the current benefits and challenges to using multiplex PCR for the detection of pathogens from gastrointestinal tract, central nervous system, lower respiratory tract, and joint specimens. The Working Group also discusses future directions and novel approaches to detection of pathogens in alternate specimen types, and outlines challenges associated with implementation of these multiplex PCR panels.
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Enfermedades Transmisibles , Patología Molecular , Humanos , Estados Unidos , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena de la Polimerasa Multiplex/métodos , Enfermedades Transmisibles/diagnósticoRESUMEN
In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and standard dose AVD IV on days 1 and 15 of each 28-day cycle for up to 6 cycles. At the time of treatment, the median patient age was 37 years, and a high-risk International Prognostic Score was observed in 46% of patients. Overall, 91% of patients received 6 cycles of AVD; 55% of patients did not receive the intended cumulative dose of BV (CDB); 28% of patients received two-thirds or less than the planned CDB. At a median follow-up time of 27.4 months (95% confidence interval [CI], 24.8-29), the median progression-free survival (PFS) was not reached, and the 12-month PFS was 90.3% (95% CI, 85.9-95.0). The impact of CDB on PFS was not significant (P = .15), nor was high CDB significantly associated with increased adverse events. In real-world experience, A + AVD is a highly effective treatment for patients with advanced-stage cHL, including for patients with prominent dose reductions of BV.
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Enfermedad de Hodgkin , Humanos , Adulto , Enfermedad de Hodgkin/terapia , Brentuximab Vedotina/uso terapéutico , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/efectos adversosRESUMEN
BACKGROUND AND OBJECTIVES: Current viral bronchiolitis guidelines exclude infants with congenital heart disease (CHD). Variations in the use of common therapeutics in this population and their associations with clinical outcomes are unknown. Our objective was to evaluate variations in (1) the use of ß-2-agonists and hypertonic saline across hospitals among infants with CHD hospitalized with bronchiolitis, and (2) hospital-level associations between medication use and outcomes. METHODS: We performed a multicenter retrospective cohort study using administrative data from 52 hospitals in the Pediatric Health Information System. We included infants ≤12 months old hospitalized from January 1, 2015 to June 30, 2019 for bronchiolitis with a secondary diagnosis of CHD. Primary exposures were the hospital-level proportion of days that patients received ß-2-agonists or hypertonic saline. Linear regression models assessed the association between the primary exposure and length of stay, 7-day readmission, mechanical ventilation use, and ICU utilization, adjusting for patient covariates and accounting for clustering by center. RESULTS: We identified 6846 index hospitalizations for bronchiolitis in infants with CHD. Overall, 43% received a ß-2-agonist, and 23% received hypertonic saline. The proportion of days with the use of ß-2-agonists (3.6% to 57.4%) and hypertonic saline (0.0% to 65.8%) varied widely across hospitals in our adjusted model. For both exposures, adjusted models revealed no association between days of use and patient outcomes. CONCLUSIONS: For children with CHD hospitalized with bronchiolitis, hospital-level use of ß-2-agonists and hypertonic saline varied widely, and their use was not associated with clinical outcomes.
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Bronquiolitis , Cardiopatías Congénitas , Humanos , Lactante , Niño , Broncodilatadores/uso terapéutico , Nebulizadores y Vaporizadores , Estudios Retrospectivos , Tiempo de Internación , Resultado del Tratamiento , Bronquiolitis/tratamiento farmacológico , Solución Salina Hipertónica/uso terapéutico , Cardiopatías Congénitas/complicacionesRESUMEN
Purpose: Purpose: Radiation therapy (RT) and the antibody-drug conjugate brentuximab vedotin (BV) are standard-of-care treatment options for patients with certain B and T-cell lymphomas; however, there are limited data exploring the safety of concurrent BV and RT (BVRT). Methods and Materials: We performed a single institutional retrospective review of 44 patients who received BVRT. Results: Twenty percent of patients (9/44) developed new grade 2 or higher (G2+) hematologic toxicity (HT) after BVRT, which was associated with radiation dose (median dose of 35 Gy in those with new G2+ HT compared with 15 Gy in those without; P < .001). Acute G2+ elevation in aspartate transaminase or alanine transaminase level was associated with administration of concurrent chemotherapy with BVRT (57% vs 21%; P = .047) but was not associated with any RT factors. Local control (LC) was achieved in 24 of 42 patients (57%) with available follow-up. Ten patients (23%) proceeded to stem cell transplant or cellular therapy after BVRT at a median of 48 days (interquartile range, 27-188 days). At last follow-up, 10 patients (23%) remained without evidence of disease. Conclusions: Our analysis demonstrates that the combination of BV and RT is well tolerated, though care should be taken during RT planning to reduce the risk of HT. This combination can be considered for patients in need of both local and systemic disease control.
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BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare inflammatory syndrome associated with SARS-CoV-2 infection. Children are increasingly admitted for MIS-C evaluation, but instead found to have alternative diagnoses. METHODS: Retrospective study of all pediatric patients <21 years of age hospitalized between August 1, 2020, and July 31, 2021, with clinical concern for MIS-C at the time of presentation were identified through use of an institutional computerized MIS-C order entry set. Final diagnoses were then collected through primary review of the medical record from the time of initial presentation through 1-month postdischarge. RESULTS: Of 359 cases identified through the MIS-C order entry set, 126 (35.1%) met criteria for MIS-C, 28 had Kawasaki Disease (KD) (7.8%), and 11 cases met criteria for both MIS-C and KD (3.1%), leaving 194 (54.0%) patients ruled out and categorized as "MIS-C mimickers." Infectious diagnoses were the most common MIS-C mimickers (78.9%). Of the infectious etiologies, bacterial (51.0%) and viral (52.3%) etiologies were seen with similar frequency. CONCLUSIONS: We describe MIS-C mimickers spanning multiple subspecialties, with infectious etiologies predominating, which can aid clinicians in the consideration of diagnostic testing, with the goal of achieving timely and accurate diagnoses.
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COVID-19 , Síndrome Mucocutáneo Linfonodular , Niño , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Estudios Retrospectivos , Cuidados Posteriores , Alta del Paciente , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome Mucocutáneo Linfonodular/diagnósticoRESUMEN
INTRODUCTION: Bacteria are the most common pathogens implicated in ascending infections in patients with cervical insufficiency. However, Candida albicans is a rare and serious cause of intra-amniotic infection that should be considered on the differential diagnosis. Upon diagnosis following cerclage placement, patients are generally advised to undergo immediate cerclage removal and discontinuation of the pregnancy due to the high risk of maternal and fetal morbidity. However, some patients decline and instead elect to continue the pregnancy with or without treatment. Limited data exist to guide management of these high-risk patients. CASE PRESENTATION: We describe a case of previable intra-amniotic C. albicans infection diagnosed following physical examination-indicated cerclage placement. The patient declined pregnancy termination and subsequently underwent systemic antifungal therapy as well as serial intra-amniotic fluconazole instillations. Fetal blood sampling confirmed transplacental transfer of maternal systemic antifungal therapy. The fetus delivered preterm and without evidence of fungemia, despite persistently positive amniotic fluid cultures. CONCLUSION: In a well-counseled patient with culture-proven intra-amniotic C. albicans infection declining termination of pregnancy, multimodal antifungal therapy in the form of systemic and intra-amniotic fluconazole administration may prevent subsequent fetal or neonatal fungemia and improve postnatal outcomes. KEY POINTS: · Candida is an uncommon cause of intra-amniotic infection in the setting of cervical insufficiency.. · Multimodal antifungal therapy may prevent fetal fungemia related to intra-amniotic Candida infection.. · Fetal blood sampling confirmed transplacental passage of fluconazole after maternal administration..