RESUMEN
Intrahepatic cholangiocarcinoma (iCCA) has previously been considered a contraindication to liver transplantation (LT). However, recent series showed favorable outcomes for LT after neoadjuvant therapy. Our center developed a protocol for neoadjuvant therapy and LT for patients with locally advanced, unresectable iCCA in 2010. Patients undergoing LT were required to demonstrate disease stability for 6 months on neoadjuvant therapy with no extrahepatic disease. During the study period, 32 patients were listed for LT and 18 patients underwent LT. For transplanted patients, the median number of iCCA tumors was 2, and the median cumulative tumor diameter was 10.4 cm. Patients receiving LT had an overall survival at 1-, 3-, and 5-years of 100%, 71%, and 57%. Recurrences occurred in seven patients and were treated with systemic therapy and resection. The study population had a higher than expected proportion of patients with genetic alterations in fibroblast growth factor receptor (FGFR) and DNA damage repair pathways. These data support LT as a treatment for highly selected patients with locally advanced, unresectable iCCA. Further studies to identify criteria for LT in iCCA and factors predicting survival are warranted.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Trasplante de Hígado , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Humanos , Trasplante de Hígado/efectos adversos , Terapia Neoadyuvante/métodosRESUMEN
OBJECTIVE: To define benchmark cutoffs for redo liver transplantation (redo-LT). BACKGROUND: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. METHODS: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. RESULTS: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks. CONCLUSION: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.
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Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Obtención de Tejidos y Órganos , Benchmarking , Enfermedad Hepática en Estado Terminal/cirugía , Supervivencia de Injerto , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Progress in deceased donor intervention research has been limited. Development of an in silico model of deceased donor physiology may elucidate potential therapeutic targets and provide an efficient mechanism for testing proposed deceased donor interventions. In this study, we report a preliminary in silico model of deceased kidney donor injury built, calibrated, and validated based on data from published animal and human studies. We demonstrate that the in silico model behaves like animal studies of brain death pathophysiology with respect to upstream markers of renal injury including hemodynamics, oxygenation, cytokines expression, and inflammation. Therapeutic hypothermia, a deceased donor intervention studied in human trials, is performed to demonstrate the model's ability to mimic an established clinical trial. Finally, future directions for developing this concept into a functional, clinically applicable model are discussed.
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Trasplante de Riñón , Obtención de Tejidos y Órganos , Animales , Muerte Encefálica , Simulación por Computador , Humanos , Donantes de TejidosRESUMEN
OBJECTIVE: This study investigated the ability of pre-transplant T-cell clonality to predict sepsis after liver transplant (LT). SUMMARY BACKGROUND DATA: Sepsis is a leading cause of death in LT recipients. Currently, no biomarkers predict sepsis before clinical symptom manifestation. METHODS: Between December 2013 and March 2018, our institution performed 478 LTs. After exclusions (eg, patients with marginal donor livers, autoimmune disorders, nonabdominal multi-organ, and liver retransplantations), 180 consecutive LT were enrolled. T-cell characterization was assessed within 48âhours before LT (immunoSEQ Assay, Adaptive Biotechnologies, Seattle, WA). Sepsis-2 and Sepsis-3 cases, defined by presence of acute infection plus ≥2 SIRS criteria, or clinical documentation of sepsis, were identified by chart review. Receiver-operating characteristic analyses determined optimal T-cell repertoire clonality for predicting post-LT sepsis. Kaplan-Meier and Cox proportional hazard modeling assessed outcome-associated prognostic variables. RESULTS: Patients with baseline T-cell repertoire clonality ≥0.072 were 3.82 (1.25, 11.40; P = 0.02), and 2.40 (1.00, 5.75; P = 0.049) times more likely to develop sepsis 3 and 12âmonths post-LT, respectively, when compared to recipients with lower (<0.072) clonality. T-cell repertoire clonality was the only predictor of sepsis 3 months post-LT in multivariate analysis (C-Statistic, 0.75). Adequate treatment resulted in equivalent survival rates between both groups: (93.4% vs 96.2%, respectively, P = 0.41) at 12âmonths post-LT. CONCLUSIONS: T-cell repertoire clonality is a novel biomarker predictor of sepsis before development of clinical symptoms. Early sepsis monitoring and management may reduce post-LT mortality. These findings have implications for developing sepsis-prevention protocols in transplantation and potentially other populations.
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Hematopoyesis Clonal/inmunología , Trasplante de Hígado , Receptores de Antígenos de Linfocitos T/inmunología , Sepsis/diagnóstico , Anciano , Biomarcadores , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Sepsis/inmunologíaRESUMEN
BACKGROUND: Careful donor-recipient matching and reduced ischemia times have improved outcomes following donation after circulatory death (DCD) liver transplantation (LT). This study examines a single-center experience with DCD LT including high-acuity and hospitalized recipients. METHODS: DCD LT outcomes were compared to a propensity score-matched (PSM) donation after brain death (DBD) LT cohort (1:4); 32 DCD LT patients and 128 PSM DBD LT patients transplanted from 2008 to 2018 were included. Analyses included Kaplan-Meier estimates and Cox proportional hazards models examining patient and graft survival. RESULTS: Median MELD score in the DCD LT cohort was 22, with median MELD of 27 for DCD LT recipients with decompensated cirrhosis. No difference in mortality or graft loss was found (p < .05) between DCD LT and PSM DBD LT at 3 years post-transplant, nor was DCD an independent risk factor for patient or graft survival. Post-LT severe acute kidney injury was similar in both groups. Ischemic-type biliary lesions (ITBL) occurred in 6.3% (n = 2) of DCD LT recipients, resulting in 1 graft loss and 1 death. CONCLUSION: This study supports that DCD LT outcomes can be similar to DBD LT, with a low rate of ITBL, in a cohort including high-acuity recipients. Strict donor selection criteria, ischemia time minimization, and avoiding futile donor/recipient combinations are essential considerations.
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Trasplante de Hígado , Obtención de Tejidos y Órganos , Muerte Encefálica , Muerte , Supervivencia de Injerto , Humanos , Puntaje de Propensión , Estudios Retrospectivos , Donantes de Tejidos , Resultado del TratamientoRESUMEN
Kidney transplant in patients with liver cirrhosis and nondialysis chronic kidney disease (CKD) is controversial. We report 14 liver cirrhotic patients who had persistently low MDRD-6 estimated glomerular filtration rate (e-GFR) <40 mL/min/1.73 m2 for ≥3 months and underwent either liver transplant alone (LTA; n=9) or simultaneous liver-kidney transplant (SLKT; n=5). Pretransplant, patients with LTA compared with SLKT had lower serum creatinine (2.5±0.73 vs 4.6±0.52 mg/dL, P=.001), higher MDRD-6 e-GFR (21.0±7.2 vs 10.3±2.0 mL/min/1.73 m2 , P=.002), higher 24-hour urine creatinine clearance (34.2±8.8 vs 18.0±2.2 mL/min, P=.002), lower proteinuria (133.2±117.7 vs 663±268.2 mg/24 h, P=.0002), and relatively normal kidney biopsy and ultrasound findings. Post-LTA, the e-GFR (mL/min/1.73 m2 ) increased in all nine patients, with mean e-GFR at 1 month (49.8±8.4), 3 months (49.6±8.7), 6 months (49.8±8.1), 12 months (47.6±9.2), 24 months (47.9±9.1), and 36 months (45.1±7.3) significantly higher compared to pre-LTA e-GFR (P≤.005 at all time points). One patient developed end-stage renal disease 9 years post-LTA and another patient expired 7 years post-LTA. The low e-GFR alone in the absence of other markers or risk factors of CKD should not be an absolute criterion for SLKT in patients with liver cirrhosis.
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Enfermedad Hepática en Estado Terminal/cirugía , Cirrosis Hepática/complicaciones , Trasplante de Hígado , Insuficiencia Renal Crónica/complicaciones , Adulto , Anciano , Toma de Decisiones Clínicas , Enfermedad Hepática en Estado Terminal/complicaciones , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/fisiopatología , Trasplante de Hígado/métodos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Estudios Retrospectivos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
BACKGROUND: Postmastectomy radiation (PMRT) in T1-T2 tumors with 1-3 positive axillary lymph nodes (ALNs) is controversial. Impact of molecular subtype (MST) on locoregional recurrence (LRR) and PMRT benefit is uncertain. We examined the association between MST and LRR, recurrence-free survival (RFS), and overall survival (OS), in T1-T2 tumors with 1-3 positive ALNs. METHODS: From an institutional database, we identified mastectomy patients with 1-3 positive ALNs between 1995 and 2006. Patients who received neoadjuvant chemotherapy, had T3-T4 tumors, or ≥4 positive ALNs were excluded. MST was defined as: hormone receptor (HR)+/HER2-(luminal A/B), HR+/HER2+(luminal HER2), HR-/HER2+(HER2), and HR-/HER2-(basal). Kaplan-Meier method and Cox regression analysis were used to examine association between MST and LRR, RFS, and OS. RESULTS: This study included 884 patients (700 no PMRT, 141 PMRT): 72.8 % luminal A/B, 7.8 % luminal HER2, 6.8 % HER2, and 12.6 % basal. Median follow-up was 6.3 years; 39 LRRs occurred. Luminal A/B subtype had the smallest tumors (p = 0.03), lowest intraductal component (p = 0.01), histologic grade (p < 0.0001), lymphovascular invasion (LVI) (p = 0.008), and multifocality/multicentricity (p = 0.02). On univariate analyses, there was no association between MST and LRR. MST was associated with RFS and OS; the basal and HER2 subtype had the lowest RFS (p = 0.0002) and OS (p < 0.0001). On multivariate analysis, only age ≤50 years (p = 0.003) and presence of LVI (p = 0.0003) were predictive of LRR; MST was not (p = 0.38). CONCLUSION: In patients with T1-T2 breast cancer and 1-3 positive lymph nodes who did not receive PMRT, MST was not an independent predictor of LRR and may not be useful in selecting PMRT candidates in that group.
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Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Mastectomía , Recurrencia Local de Neoplasia/patología , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Postmastectomy radiotherapy (PMRT) is well established in patients with ≥4 positive axillary lymph nodes (ALN); indications in 1 to 3 positive ALN remains controversial. We examined clinicopathologic criteria used for PMRT selection and compared locoregional recurrence (LRR), recurrence-free survival (RFS), and overall survival (OS) among patients with and without PMRT. METHODS: Between 1995 and 2006, a total of 1,331 patients with T1-T2 tumors and 1 to 3 positive ALN underwent mastectomy. We excluded T3/T4 tumors and neoadjuvant chemotherapy; we analyzed 1,087 patients (924 without PMRT, 163 with PMRT). Chi square testing compared clinicopathologic features between groups. The Kaplan-Meier method and Cox regression analysis examined the association between PMRT and LRR, RFS, and OS. RESULTS: PMRT patients were more likely to be ≤50 years old (p = 0.001) and to have larger tumors (p = 0.01), disease of a higher histologic grade (p = 0.03), lymphovascular invasion (LVI) (p < 0.0001), a greater number of positive ALN (p < 0.0001), extranodal invasion (p < 0.0001), and macroscopic ALN metastases (p < 0.0001). With a median follow-up of 7 years, PMRT and no-PMRT groups were similar in LRR (p = 0.57), RFS (p = 0.70), and OS (p = 0.28). On multivariate analysis of the no-PMRT group, age ≤50 years (p = 0.002) and presence of LVI (p < 0.0001) were associated with LRR. Stratified by age and LVI, patients ≤50 years old and with LVI had the highest 5-year LRR, 10.1 versus 1.1 %, than in patients >50 years old without LVI (p < 0.001). CONCLUSIONS: By using clinicopathologic features, clinicians delivered PMRT to a select group of patients with T1-T2 tumors and 1 to 3 positive ALN, resulting in similarly low rates of 5-year LRR. Among patients not receiving PMRT, age ≤50 years and LVI were associated with increased LRR rates and warrant PMRT consideration.
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Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Ganglios Linfáticos/patología , Mastectomía , Recurrencia Local de Neoplasia/patología , Selección de Paciente , Radioterapia Adyuvante , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
Previously published guidelines for the diagnosis and management of primary immune thrombocytopenia (ITP) require updating largely due to the introduction of new classes of therapeutic agents, and a greater understanding of the disease pathophysiology. However, treatment-related decisions still remain principally dependent on clinical expertise or patient preference rather than high-quality clinical trial evidence. This consensus document aims to report on new data and provide consensus-based recommendations relating to diagnosis and treatment of ITP in adults, in children, and during pregnancy. The inclusion of summary tables within this document, supported by information tables in the online appendices, is intended to aid in clinical decision making.
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Complicaciones Hematológicas del Embarazo/diagnóstico , Complicaciones Hematológicas del Embarazo/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adulto , Niño , Preescolar , Consenso , Femenino , Humanos , Masculino , Embarazo , Complicaciones Hematológicas del Embarazo/fisiopatología , Púrpura Trombocitopénica Idiopática/fisiopatologíaRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer-related mortality worldwide. Transarterial chemoembolization has shown survival benefits in patients with early to intermediate-stage HCC, becoming the standard of care and recommended treatment modality by most clinical practice guidelines. The most recent trials of the TACE plus sorafenib combined therapy in patients with unresectable HCC have yielded inconsistent outcomes. The purpose of this study was to compare the outcomes of HCC patients treated with the TACE sorafenib combination as opposed to TACE monotherapy. METHODS: This retrospective study included all patients with unresectable HCC who underwent liver transplantation and were treated by either TACE alone or TACE plus sorafenib between July 2008-December 2019. Demographic and clinical data as well as HCC recurrence post-liver transplant (LT) were reported as frequencies and proportions for categorical variables and as the median and interquartile range (IQR) or mean. Chi-square or Fisher's exact tests were performed for categorical variables and the Kruskal-Wallis test or unpaired test was performed for continuous variables. Kaplan-Meier curves present overall patient survival and HCC-free survival. RESULTS: A total of 128 patients received LT, with a median (IQR) age of 61.4 (57.0, 66.3) years; most were males (77%). Within the TACE-only group, 79 (77%) patients met the Milan criteria and 24 (23%) were beyond the Milan criteria, while the TACE plus sorafenib group had a higher proportion of patients beyond the Milan criteria: 16 (64%) vs. 9 (36%); p = 0.01. The five-year disease-free survival (DFS) between the treatment groups approached significance, with 100% DFS in the TACE plus sorafenib group vs. 67.2% in the TACE-alone group, p = 0.07. Five-year patient survival was 77.8% in the TACE plus sorafenib group compared to 61.5% in the TACE-alone group (p = 0.51). However, in patients who met the beyond Milan criteria, those who received TACE alone had a lower average amount of (percent) tumor necrosis on explant pathology (43.8% ± 32%) compared to patients who received TACE plus sorafenib (69.6% ± 32.8%, p = 0.03). CONCLUSION: This study identified that using TACE plus sorafenib is generally well-tolerated and demonstrated improved overall survival compared to TACE only in transplant recipients with unresectable HCC. A multi-center and prospective randomized controlled trial is needed to substantiate these findings.
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BACKGROUND: The management of cholangiocarcinoma is continually reviewed on a current evidence basis to develop practice guidelines and consensus statements. However, the standardized treatment guidelines are still unclear for cholangiocarcinoma patients who are listed for liver transplantation. We aimed to validate and evaluate the potential efficacy of chemotherapy combination of Gemcitabine and Cisplatin as a neo-adjuvant treatment for cholangiocarcinoma patients before liver transplantation. METHODS: In this prospective case series, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with a combination of neoadjuvant gemcitabine and cisplatin with no radiation. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center according to an open-labeled, and center-approved clinical management protocol. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. RESULTS: Between 1 March 2016, and 15 March 2022, 10 patients (8 males and 2 females) with a median age of 62.71(interquartile range: 60.02-71.87) had a confirmed diagnosis of intrahepatic or hilar cholangiocarcinoma and underwent liver transplantation. Median days of neoadjuvant therapy for a given combination of gemcitabine and cisplatin were 181 (IRQ: 120-250). Nine patients (90%) were reported with no recurrence or metastasis, and only 1 patient had confirmed metastasis (10%); days for metastasis after transplantation were 612 for this patient. All patients received a combination of gemcitabine and cisplatin as neo-adjuvant while awaiting liver transplantation. The median days of follow-up were 851 (813-967). Overall survival was 100% (95% CI 100-100%) at both years one and two; 75% (95% CI 13-96%) at years three to five. One patient died at eight hundred and eighty-five days. No adverse events were reported after liver transplantation including the patient who was confirmed with recurrence. CONCLUSIONS: Our finding demonstrated that neo-adjuvant gemcitabine and cisplatin with no radiation prior to liver transplantation resulted in excellent outcomes for patients with cholangiocarcinoma.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Trasplante de Hígado , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/cirugía , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Femenino , Humanos , Masculino , Terapia Neoadyuvante , GemcitabinaRESUMEN
Background: Cholangiocarcinoma management is constantly being updated in view of existing evidence in order to establish practice guidelines and consensus statements. However, the available treatment guidelines to optimize outcomes for cholangiocarcinoma patients who require liver transplantation are still controversial. This study contributing to the cholangiocarcinoma care field by investigating a new promising neoadjuvant therapy that might be help to grant the liver transplant option to the patients with cholangiocarcinoma. Here, we evaluate and compare the potential efficacy of chemotherapy combination of Gemcitabine plus Cisplatin versus non- Gemcitabine and Cisplatin regimens as a neo-adjuvant treatment for cholangiocarcinoma patients prior to liver transplantation. Methods: In this retrospective study, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with either the combination of neo-adjuvant Gemcitabine plus Cisplatin with no radiation or other standard options of neo-adjuvant treatment. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center in collaboration with the same institution's transplant center according to an open-labeled, and centers-approved clinical management protocol. Patients were listed for liver transplantation if they had a minimum of six months of scans showing response or confirmation of disease stability. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. This report, which was censored on March 18, 2022. Results: Out of a total of 707 liver transplant recipients were screened, 37 patients were confirmed with a diagnosis of cholangiocarcinoma and only 18 patients (11 males and 7 females) with a median age of 61.83 [interquartile range: 58.27-68.74] met inclusion criteria. Of the 18 patients enrolled, 10 received Gemcitabine/Cisplatin, while 8 patients received either Gemcitabine monotherapy or Capecitabine or FOLFIRI. Months for recurrence after transplantation was 20.1 (IRQ: 20.1-20.1) in the Gemcitabine/Cisplatin group and 9.5 (8.9-12.47) months in the non-Gemcitabine/Cisplatin group (p-value=0.18). Median months of follow-up in the Gemcitabine/Cisplatin group was 28.35 (27.1-32.23) months versus 40.12 (20.6-56.22) months in the non-Gemcitabine/Cisplatin group (p-value=0.33). In non-Gemcitabine/Cisplatin patients, overall survival was 75% (95% CI 31-93%) at both years 1 and 2; 63% (95% CI 23-86%) at years 3 to 5. In Gemcitabine/Cisplatin patients, overall survival was 100% (95% CI 100-100%) at both years 1 and 2; 75% (95% CI 13-96%) at years 3 to 5. Three non-Gemcitabine/Cisplatin patients died at 328 days, 340 days, and 896 days, respectively. One Gemcitabine/Cisplatin patient died at 885 days. Conclusion: Our findings suggest improved overall survival outcomes with Gemcitabine plus Cisplatin as neo-adjuvant treatment with no concomitant radiation compared to non-Gemcitabine/Cisplatin regimens in patients with cholangiocarcinoma prior to liver transplantation.
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BACKGROUND: Data about vaccine efficacy in solid organ transplant patients are limited. We previously reported our initial observation of a 6.2% immunogenicity rate in kidney transplant recipients (KTRs) after administration of 1 dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. We sought to report our observations of anti-SARS-CoV-2 antibody in KTRs after 2 doses of the SARS-CoV-2 mRNA vaccine. METHODS: We identified 105 KTRs who received 2 doses of the Pfizer-BioNTech or Moderna mRNA-1273 vaccine per availability and had anti-SARS-CoV-2 labs obtained at least 2 wk following administration of the second dose. Antibody testing was performed using 3 clinically validated qualitative and semiquantitative assays. RESULTS: KTRs had a 36.2% antibody response rate, whereas an age ≥68 years and a longer time from transplant were factors associated with antibody response. CONCLUSIONS: The low antibody response in KTRs may be associated with the immunosuppressive state. More data are needed to evaluate if KTRs may require higher vaccine doses or an additional booster dose to increase their ability to mount an immune response to the SARS-CoV-2 vaccine.
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Diagnosis and management of immune thrombocytopenic purpura (ITP) remain largely dependent on clinical expertise and observations more than on evidence derived from clinical trials of high scientific quality. One major obstacle to the implementation of such studies and in producing reliable meta-analyses of existing data is a lack of consensus on standardized critical definitions, outcome criteria, and terminology. Moreover, the demand for comparative clinical trials has dramatically increased since the introduction of new classes of therapeutic agents, such as thrombopoietin receptor agonists, and innovative treatment modalities, such as anti-CD 20 antibodies. To overcome the present heterogeneity, an International Working Group of recognized expert clinicians convened a 2-day structured meeting (the Vicenza Consensus Conference) to define standard terminology and definitions for primary ITP and its different phases and criteria for the grading of severity, and clinically meaningful outcomes and response. These consensus criteria and definitions could be used by investigational clinical trials or cohort studies. Adoption of these recommendations would serve to improve communication among investigators, to enhance comparability among clinical trials, to facilitate meta-analyses and development of therapeutic guidelines, and to provide a standardized framework for regulatory agencies.
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Púrpura Trombocitopénica Idiopática/clasificación , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/terapia , Terminología como Asunto , Directrices para la Planificación en Salud , Humanos , Cooperación Internacional , Estándares de Referencia , Resultado del TratamientoRESUMEN
Many researchers have investigated the possibility of using auditory evoked potentials (AEPs) to objectively diagnose tinnitus. Published AEP studies suggest differences in neural activity in individuals with tinnitus compared to control groups, but the results are not consistent. There is a great deal of variability seen in auditory evoked- and event-related potentials in the tinnitus population, which reflects AEP variability in general. At the present time, there is not a specific AEP measure able to objectively diagnose tinnitus. The auditory middle latency response (AMLR) has not been extensively examined to determine its potential as an objective measure of tinnitus; therefore, this study examined the AMLR in fourteen individuals with and without severe tinnitus to determine its potential as a diagnostic measure of tinnitus. The data from this study revealed similar AMLR results between groups. This outcome suggests that this AMLR protocol may not be specific enough to detect neurophysiological changes associated with tinnitus.
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Electrodiagnóstico/métodos , Potenciales Evocados Auditivos/fisiología , Tiempo de Reacción/fisiología , Acúfeno/diagnóstico , Acúfeno/fisiopatología , Adulto , Audiometría de Tonos Puros/métodos , Percepción Auditiva/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Patients with end-stage liver disease and pretransplant Aspergillus colonization are problematic for determining liver transplant candidacy and timing of transplantation because of concerns for posttransplant invasive aspergillosis. METHODS: We performed a retrospective review of the medical and laboratory records of all adult patients (aged ≥18 y) who underwent liver transplantation with pretransplant Aspergillus colonization at the Ronald Reagan University of California, Los Angeles, Medical Center from January 1, 2010, to December 31, 2015. RESULTS: A total of 27 patients who had Aspergillus colonization (respiratory tract 26, biliary tract 1) before liver transplantation were identified. Pretransplant characteristics included previous liver transplant (11 of 27, 40.7%), dialysis (22 of 27, 81.5%), corticosteroid therapy (12 of 27, 44.4%), intensive care unit stay (27 of 27, 100%), and median model for end-stage liver disease score of 39. Only 22.2% (6 of 27) received pretransplant antifungal agents (median duration, 5 d), whereas 100% (27 of 27) received posttransplant antifungal prophylaxis (voriconazole 81.4%, 22 of 27; echinocandin 14.8%, 4 of 27; voriconazole plus echinocandin 3.7%, 1 of 27) for median duration of 85 d. Posttransplant invasive fungal infection occurred in 14.8% (4 of 27; aspergillosis 3, mucormycosis 1). Both 6-month and 12-month survival were 66.7% (18 of 27), but only 1 death was due to fungal infection. Other causes of death were liver graft failure, intraabdominal complications, and malignancy. CONCLUSIONS: A substantial number of patients with pretransplant Aspergillus colonization can still undergo successful liver transplantation if they are otherwise suitable candidates and receive appropriate antifungal prophylaxis. Posttransplant outcome in these patients is determined mostly by noninfectious complications and not fungal infection. Pretransplant Aspergillus colonization alone should not necessarily preclude or delay liver transplantation.
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Aspergilosis/complicaciones , Aspergillus/aislamiento & purificación , Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aspergilosis/microbiología , Enfermedad Hepática en Estado Terminal/complicaciones , Enfermedad Hepática en Estado Terminal/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The application of oncology, transplant medicine, and surgery to improve patients' survival and quality of life is the core of transplant oncology. Hepatobiliary malignancies have been treated by liver transplantation (LT) with significant improved outcome. In addition, as the liver is the most common site of metastasis for colorectal cancer (CRC), patients with CRC who have stable unresectable liver metastases are good candidates for LT, and initial studies have shown improved survival compared to palliative systemic therapy. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years in a stepwise manner; however, they have only been shown to improve patient survival in the setting of limited systemic therapy options. This review illustrates the concept and history of transplant oncology as an evolving field for the management of hepatocellular carcinoma, intrahepatic biliary cancer, and liver-only metastasis of non-hepatobiliary carcinoma. The utility of immunotherapy in the transplant setting is discussed as well as the feasibility of using circulating tumor DNA for surveillance post-transplantation.
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BACKGROUND: The novel coronavirus severe acute respiratory syndrome coronavirus 2 [coronavirus disease 2019 (COVID-19)] poses unique challenges for immunosuppressed patients. Solid organ transplant (SOT) recipients comprise a large proportion of this group, yet there is limited knowledge about the presentation, clinical course, and immunosuppression management of this novel infection among heart, lung, liver, pancreas, and kidney transplant recipients. METHODS: We present 21 SOT recipients diagnosed with COVID-19 between January 1, 2020 and April 22, 2020 at a US high-volume transplant center. Diagnostic workup, clinical course, immunosuppression/antiviral management, and immediate outcomes are described. RESULTS: Twenty-one (15.9%) of 132 symptomatic patients tested were positive. Mean age at diagnosis was 54.8 ± 10.9 y. Median time from transplant was 5.58 y (interquartile range 2.25, 7.33). Median follow-up was 18 d (interquartile range 13, 30). Fourteen patients required inpatient management, with 7 (50%) placed in the intensive care unit (ICU). All transplant types were represented. Nearly 43% exhibited GI symptoms. Over half (56.2%) presented with elevated serum creatinine suggestive of acute kidney injury. The majority of patients (5/7) with concomitant infections at baseline required the ICU. Eighty percent received hydroxychloroquine ± azithromycin. Ten received toclizumab and/or ribavirin; 1 received remdesivir. Antimetabolites ± calcineurin inhibitors were held or reduced. Over half of hospitalized patients (8/14) were discharged home. Only 1 mortality (4.8%) to date, in a critically ill heart/kidney patient who had been in the ICU before diagnosis. CONCLUSIONS: COVID-19 positive SOT at our institution had favorable short-term outcomes. Those with concomitant infections had more severe illness. More data will be available to evaluate long-term outcomes and disease impact on graft function.
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Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/tratamiento farmacológico , Huésped Inmunocomprometido , Neumonía Viral/complicaciones , Neumonía Viral/tratamiento farmacológico , Receptores de Trasplantes , Adulto , Anciano , Betacoronavirus , COVID-19 , Femenino , Humanos , Terapia de Inmunosupresión , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Trasplante de Órganos , Pandemias , SARS-CoV-2 , TexasRESUMEN
INTRODUCTION: Many medical schools offer M4 boot camps to improve students' preparedness for surgical residencies. For three consecutive years, we investigated the impact of medical school boot camps on intern knot-tying and suturing skills when measured at the start of residency. METHODS: Forty-two interns completed questionnaires regarding their boot camp experiences. Their performance on knot-tying and suturing exercises was scored by three surgeons blinded to the questionnaire results. A comparison of these scores of interns with or without boot camp experiences was performed and statistical analysis applied. RESULTS: 26 of 42 (62%) interns reported boot camp training. There were no differences in scores between interns with or without a M4 boot camp experience for suturing [9.6(4.6) vs 9.8(4.1), p < 0.908], knot-tying [9.1(3.6) vs 8.4(4.1), p = 0.574], overall performance [2.0(0.6) vs 1.9(0.7), p = 0.424], and quality [2.0(0.6) vs 1.9(0.7), p = 0.665]) (mean(SD)). CONCLUSIONS: We could not demonstrate a statistically significant benefit in knot-tying and suturing skills of students who enrolled in M4 boot camp courses as measured at the start of surgical residency.
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Competencia Clínica , Educación de Postgrado en Medicina/métodos , Evaluación Educacional/métodos , Técnicas de Sutura/educación , Femenino , Humanos , Internado y Residencia , Masculino , Reproducibilidad de los Resultados , Facultades de Medicina , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Chronic immune thrombocytopenia (ITP) is a haematological disorder in which patients predominantly develop skin and mucosal bleeding. Early studies suggested ITP was primarily due to immune-mediated peripheral platelet destruction. However, increasing evidence indicates that an additional component of this disorder is immune-mediated decreased platelet production that cannot keep pace with platelet destruction. Evidence for increased platelet destruction is thrombocytopenia following ITP plasma infusions in normal subjects, in vitro platelet phagocytosis, and decreased platelet survivals in ITP patients that respond to therapies that prevent in vivo platelet phagocytosis; e.g., intravenous immunoglobulin G, anti-D, corticosteroids, and splenectomy. The cause of platelet destruction in most ITP patients appears to be autoantibody-mediated. However, cytotoxic T lymphocyte-mediated platelet (and possibly megakaryocyte) lysis, may also be important. Studies supporting suppressed platelet production include: reduced platelet turnover in over 80% of ITP patients, morphological evidence of megakaryocyte damage, autoantibody-induced suppression of in vitro megakaryocytopoiesis, and increased platelet counts in most ITP patients following treatment with thrombopoietin receptor agonists. This review summarizes data that indicates that the pathogenesis of chronic ITP may be due to both immune-mediated platelet destruction and/or suppressed platelet production. The relative importance of these two mechanisms undoubtedly varies among patients.