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PURPOSE: To investigate the effect of patient and tumor-specific characteristics on the size of immediate phase lung microwave ablation (MWA) zone and establish a prediction model. METHODS AND MATERIALS: This IRB-approved, HIPAA compliant cohort included 164 lesions from 99 patients who underwent CT-guided lung MWA and the two-dimensional elliptical ground-glass opacity ablation zone was measured. Duration, maximum temperature, tumor depth, presence of emphysema, history of ipsilateral lung ablation, surgery, and radiation were recorded. K-fold cross validation with k=5 and Least Absolute Shrinkage and Selection Operator were used to build prediction models for the major and minor axes, and area of the ablation zone. RESULTS: The median of immediate phase ablation duration was 2 minutes (IQR: 1.5 - 4.25) with 65W of power for all ablations. The mean major, minor axes, and area of ablation zone were 3.1±0.6cm, 2.0±0.5cm, and 5.1±2.1cm2. The major axis, minor axis, and area of immediate phase ablation zone dimensions were significantly associated with duration (p<0.001, p<0.001, p<0.001), maximum temperature (p<0.001, p<0.001, p<0.001), tumor depth (p=0.387, p<0.001, p<0.001), history of ipsilateral lung ablation (p=0.008, p=0.286, p=0.076), and lung radiation (p=0.001, p=0.042, p=0.015). The prediction model showed R2 values for major and minor axes and area of the ablation zone to be 0.50, 0.45, and 0.53, respectively. CONCLUSION: Duration, maximum temperature, tumor depth, history of ipsilateral lung ablation, surgery, and radiation were significantly associated with the ablation zone dimensions and size and can be used to build the prediction model to approximate the immediate phase lung MWA zone.
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Monoclonal gammopathy (MG) is a frequently detected clonal B-cell or plasma-cell disorder. Importantly, every multiple myeloma (MM) case is preceded by MG. Although clinical algorithms now allow earlier treatment of patients with biomarkers of malignancy before MM-induced tissue damage (CRAB) occurs, most patients are still diagnosed late. It is important to revisit how MG should be managed in clinical practice and whether screening is required. As the prevalence of MG and other medical co-morbidities both rise with increasing age, the degree of contribution of MG to disease states other than malignant progression is often unclear. This can lead to monitoring lapses and under recognition of the organ dysfunction that can occur with monoclonal gammopathy of clinical significance (MGCS). Therefore, models of progression to MM and/or MGCS require further refinement. While MG is currently detected incidentally, a case for screening has been made with ongoing studies in this area. Screening has the potential benefit of earlier detection and prevention of both MGCS and delayed MM presentations, but important drawbacks include the psychosocial impact on individuals and resource burden on healthcare services. MG terminology should transition alongside our increasing understanding of the condition and genomic characterization that have already begun to revise the MG nomenclature. The biology of MG has been poorly understood and is often inferred from the biology of MM, which is unhelpful. We review the literature and case for MG screening in this paper. In particular, we highlight areas that require focus to establish screening for MG.
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Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Paraproteinemias , Humanos , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Gamopatia Monoclonal de Significância Indeterminada/genética , Mieloma Múltiplo/patologia , Linfócitos B/patologia , Progressão da DoençaRESUMO
INTRODUCTION: Envarsus XR® (LCPT), a once daily dosage formulation of tacrolimus, is an FDA-approved medication in adult renal transplant recipients (RTRs). There are limited data on its pharmacokinetics (PK) in adolescent RTRs. We report here the PK profile of LCPT in adolescent RTRs. METHODS: The dose of LCPT was determined using a dose conversion ratio targeting 0.7 relative to the total daily immediate-release tacrolimus (IR-Tac) dose. On day 7 after converting to LCPT, patients had an abbreviated PK assessment with sampling at: 0 h (pre-dose), 8-, and 12-h post-dose. The PK data analysis was performed using Bayesian estimators. Our results were compared to those of published adult PK data for LCPT and pediatric PK data for IR-Tac and extended release tacrolimus (ER-Tac) formulation (Advagraf). RESULTS: PK data from three adolescent patients on LCPT were evaluated. The mean (±SD) area under the time-concentration curve (AUC) was 240 (±20.22) h*ng/mL. The mean Tmax was 9.01 ± 2.12 h, and the % fluctuation was 77.71 ± 3.96%. The AUC, Tmax , and % fluctuation were similar to reported results in adult patients taking LCPT. The AUC was higher and the Tmax was longer than what has been reported in pediatric patients taking IR-Tac and ER-Tac. In addition, the LCPT group showed a lower % fluctuation than patients receiving ER-Tac. CONCLUSION: The PK evaluation of LCPT in adolescent RTRs showed similar results to adults. Adolescents taking LCPT had a higher AUC, a more attenuated Tmax , and a lower fluctuation than that seen with ER-Tac in pediatrics.
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Transplante de Rim , Tacrolimo , Adulto , Humanos , Adolescente , Criança , Imunossupressores/efeitos adversos , Projetos Piloto , Transplante de Rim/métodos , Teorema de Bayes , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/tratamento farmacológico , Esquema de Medicação , Preparações de Ação RetardadaRESUMO
BACKGROUND: Angiotensin II type-1 receptor antibody (AT1R-Ab) has been associated with vascular injury and kidney dysfunction in pediatric kidney transplant recipients. The role of AT1R-Ab in the development of chronic kidney disease in pediatric liver and intestinal transplant recipients has not been explored. METHODS: Twenty-five pediatric intestinal transplant recipients and 79 pediatric liver transplant recipients had AT1R-Ab levels measured at varying time points in the post-transplant period. Estimated glomerular filtration rate (eGFR) was determined using creatinine based CKiD U25 equation and measured at time of AT1R-Ab measurement, at 1 year post-AT1R-Ab measurement, at 5 years post-AT1R-Ab measurement, and at the most recent routine clinic visit. The prevalence of hypertension and antihypertensive medication use were also evaluated. RESULTS: Younger age at time of AT1R-Ab measurement was associated with AT1R-Ab positivity in liver transplant recipients. There was no association between AT1R-Ab status and change in eGFR, prevalence of hypertension, or use of antihypertensive medications at the described time points. CONCLUSIONS: AT1R-Ab positivity was not associated with a decline in eGFR or hypertension in pediatric liver and intestinal transplant recipients. Further studies are needed using other markers of kidney function, such as cystatin C, to validate this finding. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Hipertensão , Transplante de Rim , Humanos , Criança , Transplante de Rim/efeitos adversos , Receptor Tipo 1 de Angiotensina , Anti-Hipertensivos , Transplantados , Rejeição de Enxerto , Anticorpos , Fígado , RimRESUMO
INTRODUCTION: Recognition of stroke by Emergency Medical Services (EMS) is critical to initiate rapid emergency department treatment. Most prehospital stroke screening tools rely heavily on presentation with the classic symptoms of facial droop, speech changes, unilateral weakness. However, women may be less likely to present with classic symptoms and may also have different distributions of stroke by anatomical location. This study seeks to determine the association between biological sex, presentation with classic symptoms, and the location of the infarcted tissue. METHODS: This is a retrospective cohort study. Data from electronic health records were extracted for patients with acute ischemic stroke who presented via EMS to a single Comprehensive Stroke Center between January 1, 2018 and December 31, 2020. We used descriptive statistics characterize the cohort. Multivariable logistic regression identified factors associated with classic symptom presentation (facial droop, speech changes, and/or unilateral weakness). Biological sex, location of the infarct, stroke etiology, age and the interaction between sex and infarct location were assessed as covariates. RESULTS: There were 364 (58.6%) males and 257 (41.1%) females with an acute ischemic stroke included in this study. EMS documented one or more classic symptoms in 125 (72.3%) males and 161 (67.9%) females. There were no baseline differences in infarct location or presentation with classic symptoms as documented by EMS comparing males and females. Multivariate logistic regression found no association between biological sex and presentation with classic symptoms (Odds Ratio 1.08; 95% CI 0.58 to 1.55) after controlling for age, stroke location, etiology of stroke or the interaction between sex and infarct location. Presence of an anterior circulation infarct compared to posterior circulation infarct was positively associated with a classic presentation to EMS (Odds Ratio 3.41; 95% CI 2.15 to 5.41). CONCLUSIONS: This study found no difference in the frequency of patient presentation with classic stroke symptoms based on biological sex alone, nor a significant different in distribution of infarcts between males and females. Infarct location (i.e., involving the anterior circulation) was associated with a classic presentation. This suggests that the likelihood of presenting with classic stroke symptoms is not influenced by sex, but rather the location of the infarct.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Isquemia Encefálica/terapia , Estudos Retrospectivos , Caracteres Sexuais , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , InfartoRESUMO
OBJECTIVE: To report current diagnostic protocols, practices, and barriers related to imaging of alveolar clefting among American Cleft Palate-Craniofacial Association (ACPA)-approved cleft/craniofacial teams. METHODS: An electronic survey was sent to 162 ACPA-approved teams in the United States. Key items were team location, venue of orthodontic treatment, imaging modality(s) and access, barriers to imaging, billing, imaging protocols including team members involved in decisions pre- and post-alveolar bone grafting (ABG), and craniofacial fellowship status of team orthodontist(s). RESULTS: A total of 66 responses were received (40.7%). Responding teams were university-based (47%), hospital-based (42.4%), and independent clinics (10.6%). Orthodontic treatment for most patients was in private practice (53%). On-site 2-dimensional (2D) and 3-dimensional (3D) dental imaging capabilities were reported by 42% of teams; 29% have no on-site imaging. One or more barrier(s) to acquiring imaging were reported by 67%, with insurance challenges reported by 47%. Most teams bill medical payors for cleft-related dental imaging (58%). Pre- and post-ABG imaging was most frequently 3D (35% and 36%, respectively). Surgeons and orthodontists commonly evaluate ABG timing and outcome together (53%-65%). Periapical radiographs were included significantly more often in cleft imaging protocols by orthodontists with versus without fellowship training (P = .011, P = .04). CONCLUSIONS: Barriers to acquiring imaging are frequent. 3D is the most common imaging pre- and post-ABG. Our study endorses multi-level advocacy for improved medical insurance coverage of diagnostic cleft-related dental imaging to decrease barriers to providing timely care.
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Enxerto de Osso Alveolar , Fenda Labial , Fissura Palatina , Humanos , Estados Unidos , Fenda Labial/diagnóstico por imagem , Fenda Labial/cirurgia , Fissura Palatina/diagnóstico por imagem , Fissura Palatina/cirurgia , Enxerto de Osso Alveolar/métodos , Ortodontistas , Inquéritos e QuestionáriosRESUMO
Allogeneic haematopoietic stem cell transplant (HSCT) recipients remain at high risk of adverse outcomes from coronavirus disease 2019 (COVID-19) and emerging variants. The optimal prophylactic vaccine strategy for this cohort is not defined. T cell-mediated immunity is a critical component of graft-versus-tumour effect and in determining vaccine immunogenicity. Using validated anti-spike (S) immunoglobulin G (IgG) and S-specific interferon-gamma enzyme-linked immunospot (IFNγ-ELIspot) assays we analysed response to a two-dose vaccination schedule (either BNT162b2 or ChAdOx1) in 33 HSCT recipients at ≤2 years from transplant, alongside vaccine-matched healthy controls (HCs). After two vaccines, infection-naïve HSCT recipients had a significantly lower rate of seroconversion compared to infection-naïve HCs (25/32 HSCT vs. 39/39 HCs no responders) and had lower S-specific T-cell responses. The HSCT recipients who received BNT162b2 had a higher rate of seroconversion compared to ChAdOx1 (89% vs. 74%) and significantly higher anti-S IgG titres (p = 0.022). S-specific T-cell responses were seen after one vaccine in HCs and HSCT recipients. However, two vaccines enhanced S-specific T-cell responses in HCs but not in the majority of HSCT recipients. These data demonstrate limited immunogenicity of two-dose vaccination strategies in HSCT recipients, bolstering evidence of the need for additional boosters and/or alternative prophylactic measures in this group.
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Vacinas contra COVID-19 , COVID-19 , Transplante de Células-Tronco Hematopoéticas , Fatores Etários , Anticorpos Antivirais/imunologia , Vacina BNT162/imunologia , Vacina BNT162/uso terapêutico , Transplante de Medula Óssea/efeitos adversos , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/farmacologia , Vacinas contra COVID-19/uso terapêutico , ChAdOx1 nCoV-19/imunologia , ChAdOx1 nCoV-19/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/imunologia , Imunidade Humoral/efeitos dos fármacos , Imunidade Humoral/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Soroconversão , Transplante Homólogo/efeitos adversos , Vacinação/efeitos adversosRESUMO
OBJECTIVES: Soluble receptor for advanced glycation end products is a known plasma marker of alveolar epithelial injury. However, RAGE is also expressed on cell types beyond the lung, and its activation leads to up-regulation of pro-inflammatory mediators. We sought to examine the relationship between plasma soluble receptor for advanced glycation end products and primary pulmonary dysfunction, extrapulmonary organ dysfunction, and mortality in pediatric acute respiratory distress syndrome patients at two early time points following acute respiratory distress syndrome diagnosis and compare these results to plasma surfactant protein-D, a marker of pure alveolar epithelial injury. DESIGN: Prospective observational study. SETTING: Five academic PICUs. PATIENTS: Two hundred fifty-eight pediatric patients 30 days to 18 years old meeting Berlin Criteria for acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma was collected for soluble receptor for advanced glycation end products and surfactant protein-D measurements within 24 hours (day 1) and 48 to 72 hours (day 3) after acute respiratory distress syndrome diagnosis. Similar to surfactant protein-D, plasma soluble receptor for advanced glycation end products was associated with a higher oxygenation index (p < 0.01) and worse lung injury score (p < 0.001) at the time of acute respiratory distress syndrome diagnosis. However, unlike surfactant protein-D, plasma soluble receptor for advanced glycation end products was associated with worse extrapulmonary Pediatric Logistic Organ Dysfunction score during ICU stay (day 3; p < 0.01) and positively correlated with plasma levels of interleukin-6 (p < 0.01), tumor necrosis factor-α (p < 0.01), and angiopoietin-2 (p < 0.01). Among children with indirect lung injury, plasma soluble receptor for advanced glycation end products was associated with mortality independent of age, sex, race, cancer/bone marrow transplant, and Pediatric Risk of Mortality score (day 3; odds ratio, 3.14; 95% CI, 1.46-6.75; p < 0.01). CONCLUSIONS: Unlike surfactant protein-D, which is primarily localized to the alveolar epithelium plasma soluble receptor for advanced glycation end products is systemically expressed and correlates with markers of inflammation, extrapulmonary multiple organ dysfunction, and death in pediatric acute respiratory distress syndrome with indirect lung injury. This suggests that unlike surfactant protein-D, soluble receptor for advanced glycation end products is a multifaceted marker of alveolar injury and increased inflammation and that receptor for advanced glycation end products activation may contribute to the pathogenesis of multiple organ failure among children with indirect acute respiratory distress syndrome.
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Lesão Pulmonar , Síndrome do Desconforto Respiratório , Adolescente , Biomarcadores , Criança , Pré-Escolar , Epitélio , Produtos Finais de Glicação Avançada , Humanos , Lactente , Recém-Nascido , Inflamação , Pulmão , Proteína D Associada a Surfactante Pulmonar , Receptor para Produtos Finais de Glicação Avançada , TensoativosRESUMO
BACKGROUND: Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes. METHODS: This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS). RESULTS: For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND. CONCLUSION: This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.
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Melanoma , Neoplasias Cutâneas , Humanos , Excisão de Linfonodo/métodos , Melanoma/patologia , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/patologiaRESUMO
B-cell prolymphocytic leukaemia (B-PLL) is an aggressive B-cell lymphoproliferative disease with few clinically proven targeted treatments. Due to the rarity of the condition, there is a paucity of clinical trial data and none that involve targeted inhibitors. We present a unique case of relapsed refractory B-PLL treated to a sustained minimal residual disease-negative remission with venetoclax monotherapy, to add to the current evidence base and rationale for future studies using BCL-2 inhibitors in B-PLL.
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Leucemia Linfocítica Crônica de Células B , Leucemia Prolinfocítica Tipo Células B , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Prolinfocítica Tipo Células B/diagnóstico , Leucemia Prolinfocítica Tipo Células B/tratamento farmacológico , Leucemia Prolinfocítica Tipo Células B/etiologia , Neoplasia Residual , Proteínas Proto-Oncogênicas c-bcl-2/genética , Sulfonamidas , Proteína Supressora de Tumor p53RESUMO
BACKGROUND: Treatment options for antibody-mediated rejection (AMR) are limited. Recent studies have shown that inhibition of interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R) signaling can reduce inflammation and slow AMR progression. METHODS: We report our experience using monthly tocilizumab (anti-IL6R) in 25 pediatric renal transplant recipients with AMR, refractory to IVIg/Rituximab. From January 2013 to June 2019, a median (IQR) of 12 (6.019.0) doses of tocilizumab were given per patient. Serial assessments of renal function, biopsy findings, and HLA DSA (by immunodominant HLA DSA [iDSA] and relative intensity score [RIS]) were performed. RESULTS: Median (IQR) time from transplant to AMR was 41.4 (24.367.7) months, and time from AMR to first tocilizumab was 10.6 (8.317.6) months. At median (IQR) follow up of 15.8 (8.435.7) months post-tocilizumab initiation, renal function was stable except for 1 allograft loss. There was no significant decrease in iDSA or RIS. Follow up biopsies showed reduction in peritubular capillaritis (p = .015) and C4d scoring (p = .009). The most frequent adverse events were cytopenias. CONCLUSIONS: Tocilizumab in pediatric patients with refractory AMR was well tolerated and appeared to stabilize renal function. The utility of tocilizumab in the treatment of AMR in this population should be further explored.
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Isoanticorpos , Transplante de Rim , Anticorpos Monoclonais Humanizados , Biópsia , Criança , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Antígenos HLA , Humanos , Rim/patologia , Rim/fisiologia , Transplante de Rim/efeitos adversosRESUMO
BACKGROUND: Understanding the long-term sequelae of severe COVID-19 remains limited, particularly in the United States. OBJECTIVE: To examine long-term outcomes of patients who required intensive care unit (ICU) admission for severe COVID-19. DESIGN, PATIENTS, AND MAIN MEASURES: This is a prospective cohort study of patients who had severe COVID-19 requiring an ICU admission in a two-hospital academic health system in Southern California. Patients discharged alive between 3/21/2020 and 12/31/2020 were surveyed approximately 6 months after discharge to assess health-related quality of life using Patient-Reported Outcomes Measurement Information System (PROMIS®)-29 v2.1, post-traumatic stress disorder (PTSD) and loneliness scales. A preference-based health utility score (PROPr) was estimated using 7 PROMIS domain scores. Patients were also asked their attitude about receiving aggressive ICU care. KEY RESULTS: Of 275 patients admitted to the ICU for severe COVID-19, 205 (74.5%) were discharged alive and 132 (64%, median age 59, 46% female) completed surveys a median of 182 days post-discharge. Anxiety, depression, fatigue, sleep disturbance, ability to participate in social activities, pain interference, and cognitive function were not significantly different from the U.S. general population, but physical function (44.2, SD 11.0) was worse. PROPr mean score of 0.46 (SD 0.30, range -0.02 to 0.96 [<0 is worse than dead and 1 represents perfect health]) was slightly lower than the U.S. general population, with an even distribution across the continuum. Poor PROPr was associated with chronic medical conditions and receipt of life-sustaining treatments, but not demographics or social vulnerability. PTSD was suspected in 20% and loneliness in 29% of patients. Ninety-eight percent of patients were glad they received life-saving treatment. CONCLUSION: Most patients who survive severe COVID-19 achieve positive outcomes, with health scores similar to the general population at 6 months post-discharge. However, there is marked heterogeneity in outcomes with a substantial minority reporting severely compromised health.
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COVID-19 , Qualidade de Vida , Assistência ao Convalescente , COVID-19/terapia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Estudos ProspectivosRESUMO
OBJECTIVE: There are limited data on the efficacy and tolerability of VCD chemotherapy in transplant-non-eligible (TNE) newly diagnosed myeloma (NDMM) patients. In this retrospective study, we set out to evaluate this triplet combination in this setting across Thames Valley Cancer Network (UK). METHODS: The primary end point was overall response rate (ORR). Secondary outcomes included event-free survival (EFS), overall survival (OS) and adverse events (AEs). RESULTS: In a total cohort of 158 patients, ORR for total cohort was 72.1%. Median EFS was 10.5 months, and for subgroups by age (<75:11.7 vs ≥75:10.3 months, P = .124), by Charlson Co-morbidity Index (CCI) (<5:11.1 vs ≥5:8.2 months, P = .345). The 4-month landmark analysis showed the following median EFS results: by cumulative bortezomib dose (≥26 mg/m2 : 9.0 months vs <26 mg/m2 : 6.4, P = .13), by cumulative cyclophosphamide dose (≥7000 mg: 9.2 vs <7000 mg: 7.0 months, P = .02) and by cumulative dexamethasone dose (>600 mg: 7.8 vs ≤600 mg: 8.3 months, P = .665). Median OS was 46.9 months. The incidence rate of AE was as follows: any grade (76.8%), ≥G3 (27.1%), ≥G3 haematological AEs (7.9%), any grade infections (31.1%) and ≥G3 infections (11.9%). CONCLUSION: This study demonstrated a good ORR achieved from fixed duration VCD, which was reasonably well tolerated. This was followed by modest median EFS. We envisage that the latter may be improved in this patient group with the use of a higher cumulative bortezomib dose (≥26 mg/m2 ) which showed a trend for improved EFS although without statistical significance (P = .13), and with the use of a higher cumulative cyclophosphamide doses (≥7000 mg, P = .02), subject to tolerability and close monitoring.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Tomada de Decisão Clínica , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Gerenciamento Clínico , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Prognóstico , Teniposídeo/efeitos adversos , Teniposídeo/uso terapêutico , Resultado do Tratamento , Reino Unido/epidemiologiaRESUMO
IgM paraprotein-associated peripheral neuropathy (PN) in patients without overt evidence of lymphoma is a recognised clinical entity of unknown aetiology. Interrogating the bone marrow B-cell or plasma cell clones underlying paraproteinemic neuropathies may improve our understanding of both pathogenesis and treatment options. This retrospective observational analysis of IgM paraprotein-associated PN identified five patients with small pathological MYD88 L265P and CD20-positive B-cell clones in their bone marrow using multi-parametric flow cytometry, who have shown durable neurological response to rituximab. We posit that multi-parametric flow cytometry may be instrumental in identifying the cellular source of the paraprotein in IgM paraprotein-associated PN, and thus directing appropriate immunomodulatory therapy. Further understanding of these small pathological B-cell clones may also provide additional insight into mechanisms of monoclonal gammopathy of clinical significance overall.
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Antígenos CD20/sangue , Linfócitos B/metabolismo , Imunoglobulina M/sangue , Paraproteinemias , Paraproteínas/metabolismo , Doenças do Sistema Nervoso Periférico , Rituximab/administração & dosagem , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Paraproteinemias/sangue , Paraproteinemias/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/sangue , Doenças do Sistema Nervoso Periférico/tratamento farmacológicoRESUMO
OBJECTIVES: We sought to characterise the outcomes of patients with haematological malignancy and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hospital in our regional network of 7 hospitals. METHODS: Consecutive hospitalised patients with haematological malignancy and SARS-CoV-2 infection were identified from 01/03/2020 to 06/05/2020. Outcomes were categorised as death, resolved or ongoing. The primary outcome was preliminary case fatality rate (pCFR), defined as the number of cases resulting in death as a proportion of all diagnosed cases. Analysis was primarily descriptive. RESULTS: 66 Patients were included, overall pCFR was 51.5%. Patients ≥ 70 years accounted for the majority of hospitalised cases (42, 63%) and fatalities (25, 74%). Mortality was similar between females (52%) and males (51%). Immunosuppressive or cytotoxic treatment within 3 months of the diagnosis of SARS-CoV-2 infection was associated with a significantly higher pCFR of 70%, compared with 28% in those not on active treatment (P = .0013, 2 proportions z test). CONCLUSIONS: Mortality rates in patients with haematological malignancy and SARS-CoV-2 infection in hospital are high supporting measures to minimise the risk of infection in this population.
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COVID-19/complicações , Neoplasias Hematológicas/complicações , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , COVID-19/mortalidade , COVID-19/prevenção & controle , Citotoxinas/efeitos adversos , Feminino , Neoplasias Hematológicas/terapia , Hospitalização , Humanos , Terapia de Imunossupressão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , SARS-CoV-2 , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: To evaluate the risk factors for mortality in pediatric extracorporeal membrane oxygenation patients. DESIGN: Retrospective, single-center study. SETTING: PICU and Pediatric cardiothoracic ICU in an urban, quaternary care center. PATIENTS: All neonatal and pediatric patients requiring extracorporeal membrane oxygenation at our institution between January 2014 and December 2018, who underwent a standardized continuous electroencephalogram neuromonitoring protocol during most of the duration of extracorporeal membrane oxygenation support. We excluded patients who had extracorporeal membrane oxygenation initiated at another institution. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sixty-six children required extracorporeal membrane oxygenation support during this period. Four patients were excluded, three due to lack of electroencephalogram data, one with extracorporeal membrane oxygenation initiated at other institution. In the remaining 62, 11 patients (17%) had seizures, of which 5 (45%) had status epilepticus. Eight of 11 patients (72%) had exclusively electrographic seizures. A total of 33 patients (53.2%) died, of which 22 died during extracorporeal membrane oxygenation course, and one died 3 years after hospital discharge. Mean survival from extracorporeal membrane oxygenation initiation was 766.9 days (standard deviation, 691.7; median, 546.5; interquartile range 1-3, 97.7-1255.0). In multivariate analysis, increased risk of mortality was associated with the use of extracorporeal cardiopulmonary resuscitation (hazard ratio, 4.33; 95% CI, 1.75-10.72; p = 0.002), imaging findings of cerebral edema (hazard ratio, 14.31; 95% CI, 5.18-39.54; p < 0.001), high lactate level (> 100 mg/dL within 2 hr preextracorporeal membrane oxygenation) (hazard ratio, 1.22; 95% CI, 1.03-1.44; p = 0.022), and prolonged deep hypothermic circulatory arrest (hazard ratio, 3.43; 95% CI, 1.65-7.13; p < 0.001). Presence of seizures was associated with imaging findings of cerebral edema (hazard ratio, 4.16; 95% CI, 1.04-16.58; p = 0.04). CONCLUSIONS: Seizures are common in children requiring extracorporeal membrane oxygenation support, with a high rate of electrographic seizures and status epilepticus, as in prior studies. Presence of cerebral edema is both risk factor for mortality and seizures. Other risk factors for mortality include extracorporeal cardiopulmonary resuscitation, high lactate levels, and prolonged deep hypothermic circulatory arrest.
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Oxigenação por Membrana Extracorpórea , Criança , Oxigenação por Membrana Extracorpórea/efeitos adversos , Mortalidade Hospitalar , Humanos , Lactente , Prevalência , Estudos Retrospectivos , Fatores de Risco , Convulsões/diagnóstico , Convulsões/epidemiologiaAssuntos
Vacinas contra COVID-19 , COVID-19 , Mieloma Múltiplo , SARS-CoV-2 , Vacinação , Humanos , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , SARS-CoV-2/imunologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos LongitudinaisRESUMO
Idiopathic pulmonary fibrosis is the commonest interstitial lung disease. Radiologists play an essential role in making an accurate diagnosis, and this is necessary given its prognostic implications and potential use of antifibrotic therapies. This review highlights the radiologic features and imaging classification of fibrosis with reference to recently updated international guidelines and emphasizing the importance of the multidisciplinary team in idiopathic pulmonary fibrosis diagnosis and, in particular, when pathological sampling is required.
Assuntos
Fibrose Pulmonar Idiopática/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Guias de Prática Clínica como Assunto , Prognóstico , Interpretação de Imagem Radiográfica Assistida por Computador , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Distal renal tubular acidosis (dRTA) is associated with renal stone disease, and it often needs to be considered and excluded in some recurrent calcium kidney stone formers (KSFs). However, a diagnosis of dRTA, especially when 'incomplete', can be missed and needs to be confirmed by a urinary acidification (UA) test. The gold standard reference test is still the short ammonium chloride (NH4Cl) test, but it is limited by gastrointestinal side effects and occasionally failure to ingest sufficient NH4Cl. For this reason, the furosemide plus fludrocortisone (F+F) test has been proposed as an easier and better-tolerated screening test. The aim of the present study was to assess the usefulness of the F+F test as a clinical screening tool for dRTA in a renal stone clinic. METHODS: We studied 124 patients retrospectively in whom incomplete dRTA was suspected: 71 had kidney stones only, 9 had nephrocalcinosis only and 44 had both. A total of 158 UA tests were performed: 124 F+F and 34 NH4Cl; both tests were completed in 34 patients. RESULTS: The mean age was 45.4 ± 15 years, and 49% of patients were male. The prevalence of complete and incomplete dRTAs was 7 and 13.7%, respectively. Of the 34 patients tested using both tests, 17 (50%) were abnormal and 4 (12%) were normal. Thirteen (39%) patients were abnormal by F+F, but normal by NH4Cl [sensitivity 100% (95% CI 80-100), specificity 24% (95% CI 7-50), positive predictive value 57% (95% CI 37-75), negative predictive value 100% (95% CI 40-100)]. CONCLUSIONS: The F+F test is characterized by an excellent sensitivity and negative predictive value, and the diagnosis of incomplete dRTA can be excluded reliably in a patient who acidifies their urine normally with this test. However, its lack of specificity is a drawback, and if there is any doubt, an abnormal F+F test may need to be confirmed by a follow-up NH4Cl test. Ideally, a prospective blinded study in unselected KSFs is needed to accurately assess the reliability of the F+F test in diagnosing, rather than excluding, dRTA.