Correction to: Amanita Mushroom Toxin Poisoning in Los Angeles County.

[This corrects the article DOI: 10.14309/crj.0000000000001246.].

Amanita Mushroom Toxin Poisoning in Los Angeles County.

Mushroom (amatoxin) poisoning from ingestion is a rare but life-threatening medical emergency characterized by gastrointestinal symptoms before progression to multisystem organ failure in severe cases. Many therapies of amatoxin intoxication have been described, including supportive care, medical therapies, detoxification strategies, and liver transplant. The evidence supporting these therapies remains limited due to the rarity of amatoxin poisoning and challenge of a timely diagnosis. We report a case of amatoxin poisoning in Los Angeles causing severe liver injury without acute liver failure treated successfully using medical therapies, gallbladder drainage, and plasma exchange.

How do we design a laboratory space for a hospital transfusion medicine service?

BACKGROUND: Transfusion service laboratories (TSL) often need to renovate or design new laboratory space, and their leaders must be involved in the complex and multifaceted design process. STUDY DESIGN AND METHODS: This manuscript outlines the design process and considerations for a dedicated TSL space. RESULTS: Proactive engagement with key collaborators throughout the design process is essential. Major design considerations include physical features such as location, size, service/equipment needs, and zones within the laboratory; intangible issues such as efficiency, well-being, and disaster planning; and adaptations for suboptimal space and changes over time. CONCLUSION: Investing in the design of the laboratory space facilitates high-quality TSL operations, productivity, customer satisfaction, regulatory compliance, staff well-being, and most importantly, patient safety.

Durable remission of thrombotic thrombocytopenic purpura in the setting of pembrolizumab therapy.

BACKGROUND: There is a small but growing number of thrombotic thrombocytopenic purpura (TTP) cases attributed to immune checkpoint inhibitor therapy, with nivolumab and ipilimumab therapy being the most frequently described in the literature. STUDY DESIGN AND METHODS: This report evaluates the course of a patient with a history of metastatic adenocarcinoma of the lung who developed TTP following treatment with the PD-1 inhibitor Pembrolizumab. The patient was treated with six sessions of therapeutic plasma exchange and appeared to be in remission. Exacerbation occurred 4 days later, and seven more sessions of plasma exchange were performed along with four total doses of Rituximab, and a steroid taper with monitoring of platelet counts and ADAMTS13 activity. RESULTS: His platelet count recovered to a peak of 318,000 UL with an ADAMTS13 activity of 77% at the time of discharge. The patient has been following up regularly for outpatient testing with no TTP relapse as of the completion of this report. DISCUSSION: This is one of a few cases of Pembrolizumab-associated TTP reported in the literature with successful complete remission following treatment. Plasma exchange in this setting may be an especially beneficial therapeutic intervention because of the removal of both the anti-ADAMTS13 antibody as well as the immune system upregulating anti-PDL1 monoclonal antibody with replacement of ADAMTS13 from donor plasma. Longer duration of plasma exchange and monitoring for normalization of ADAMTS13 levels in addition to platelet count before cessation of treatment may improve durable remission rates in this entity.

Successful autologous hematopoietic stem cell transplants using Salmonella positive products collected from asymptomatic donors.

BACKGROUND: Bacterial contamination of hematopoietic stem cell (HSC) products is most commonly due to normal skin flora. Salmonella in HSC products is rare, and to our knowledge safe administration of an autologous HSC product containing Salmonella has not been reported. STUDY DESIGN AND METHODS: We describe two patients undergoing autologous HSC transplant: peripheral blood HSC collection was performed by leukapheresis, and samples were cultured according to standard institutional protocol. Subsequent microorganism identification was performed using MALDI-TOF (Bruker Biotyper). Strain-relatedness was investigated by infrared spectroscopy using the IR Biotyper (Bruker). RESULTS: The patients were asymptomatic throughout the collection process; however, HSC products collected on two consecutive days from each patient were positive for Salmonella. Isolates from both cultures were further characterized as Salmonella enterica serovar Dublin by the local public health department. Antibiotic susceptibility testing revealed different sensitivity patterns for the two strains. IR Biotyper demonstrated significant discriminatory power among the clinically significant Salmonella enterica subspecies, serogroups B, C1, and D. The patient strains were similar as both belonged to Group D Salmonella enterica serovar Dublin but were not identical. The Salmonella positive autologous HSC products were infused to both patients following administration of empiric antibiotic therapy. Both patients successfully engrafted and did well. CONCLUSION: Salmonella is rarely seen in cellular therapy products and positivity may be the result of asymptomatic bacteremia at the time of collection. We present two instances of autologous HSC products containing Salmonella that were infused, along with prophylactic antimicrobial therapy without significant adverse clinical effects.

Intralesional Meglumine Antimoniate: Safe, Feasible and Effective Therapy for Cutaneous Leishmaniasis in Bolivia.

The standard of care for cutaneous leishmaniasis includes the intramuscular/intravenous administration of pentavalent antimonials that are toxic and poorly tolerated. Primary health care usually lacks trained health staff for the diagnosis and treatment of leishmaniasis in Cochabamba Bolivia. Taking these aspects into account, a Bolivian consortium set out to explore the intralesional administration of meglumine antimoniate to treat cutaneous leishmaniasis during primary care under programmatic conditions. A four-step strategy consisting of clinical training for intralesional treatment and the promotion and periodic follow-up of health staff was carried out. The training process was applied in situ to personnel of nine primary health care centres. The intralesional treatment was applied five times every other day. Clinical follow-up after six-months of treatment showed a 77% healing proportion and 5% of therapeutic failure among 152 enrolled patients. The drug volume used in the intralesional procedure was on average 1.7 mL/ulcer treated. In conclusion, the strategy used was successful and effective, accomplishing a healing proportion similar to the long standardized treatment with a reduced time of administration, no severe side effects, and it is feasible to conduct by trained health staff. Our study supports the current PAHO/WHO recommendation for the intralesional administration of pentavalent antimonials for the treatment of cutaneous leishmaniasis.

Diastolic shock index and clinical outcomes in patients with septic shock.

BACKGROUND: Loss of vascular tone is a key pathophysiological feature of septic shock. Combination of gradual diastolic hypotension and tachycardia could reflect more serious vasodilatory conditions. We sought to evaluate the relationships between heart rate (HR) to diastolic arterial pressure (DAP) ratios and clinical outcomes during early phases of septic shock. METHODS: Diastolic shock index (DSI) was defined as the ratio between HR and DAP. DSI calculated just before starting vasopressors (Pre-VPs/DSI) in a preliminary cohort of 337 patients with septic shock (January 2015 to February 2017) and at vasopressor start (VPs/DSI) in 424 patients with septic shock included in a recent randomized controlled trial (ANDROMEDA-SHOCK; March 2017 to April 2018) was partitioned into five quantiles to estimate the relative risks (RR) of death with respect to the mean risk of each population (assumed to be 1). Matched HR and DAP subsamples were created to evaluate the effect of the individual components of the DSI on RRs. In addition, time-course of DSI and interaction between DSI and vasopressor dose (DSI*NE.dose) were compared between survivors and non-survivors from both populations, while ROC curves were used to identify variables predicting mortality. Finally, as exploratory observation, effect of early start of vasopressors was evaluated at each Pre-VPs/DSI quintile from the preliminary cohort. RESULTS: Risk of death progressively increased at gradual increments of Pre-VPs/DSI or VPs/DSI (One-way ANOVA, p < 0.001). Progressive DAP decrease or HR increase was associated with higher mortality risks only when DSI concomitantly increased. Areas under the ROC curve for Pre-VPs/DSI, SOFA and initial lactate were similar, while mean arterial pressure and systolic shock index showed poor performances to predict mortality. Time-course of DSI and DSI*NE.dose was significantly higher in non-survivors from both populations (repeated-measures ANOVA, p < 0.001). Very early start of vasopressors exhibited an apparent benefit at higher Pre-VPs/DSI quintile. CONCLUSIONS: DSI at pre-vasopressor and vasopressor start points might represent a very early identifier of patients at high risk of death. Isolated DAP or HR values do not clearly identify such risk. Usefulness of DSI to trigger or to direct therapeutic interventions in early resuscitation of septic shock need to be addressed in future studies.

Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis.

BACKGROUND: Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock. METHODS: A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h. RESULTS: Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0-510] vs. 1500[650-2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500-1900] vs. 2600[1600-3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17-0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h. CONCLUSION: A very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes.

RHD genotyping of serologic RhD-negative blood donors in a hospital-based blood donor center.

BACKGROUND: Serologic RhD-negative blood donors are tested by a method known to detect weak D antigen expression. Serology does not detect all red blood cells with RhD expression and RHD genotyping has been used to identify variant RHD alleles, which may lead to some RhD expression. The aim of this study was to determine the frequency of RHD variant alleles in serologic RhD-negative blood donors at a hospital-based donor center in Los Angeles. STUDY DESIGN AND METHODS: RHD genotyping of serologic RhD-negative blood donors over a 20-month period was performed using the Immucor RHD BeadChip assay. DNA sequencing was performed when the RHD BeadChip assay failed to assign a genotype. For RHD variants known or suspected to result in RhD expression, recipients of previous blood donations were investigated for alloimmunization. RESULTS: RHD genotyping was performed in 1174 RhD-negative blood donors, and 1122 were genotyped for RHCE variants. Eleven donors (0.94%) harbored mutations predicted to yield RhD expression. The predicted phenotypes were, in decreasing frequency, DEL, partial, and weak D phenotypes. Anti-D was not detected in 16 patients who had received blood from these donors after an average follow up of 182 days. CONCLUSION: Genotyping can be used to identify donors with the potential to sensitize RhD-negative recipients. In this limited study, 0.94% of serologic RhD-negative blood donors were found to have variant RHD alleles that might cause alloimmunization in RhD-negative recipients. To our knowledge, a study of this nature has not been reported in the United States.

A Double Fail-Safe Approach to Prevent Tumorigenesis and Select Pancreatic ß Cells from Human Embryonic Stem Cells.

The transplantation of human embryonic stem cell (hESC)-derived insulin-producing ß cells for the treatment of diabetes is finally approaching the clinical stage. However, even with state-of-the-art differentiation protocols, a significant percentage of undefined non-endocrine cell types are still generated. Most importantly, there is the potential for carry-over of non-differentiated cell types that may produce teratomas. We sought to modify hESCs so that their differentiated progeny could be selectively devoid of tumorigenic cells and enriched for cells of the desired phenotype (in this case, ß cells). Here we report the generation of a modified hESC line harboring two suicide gene cassettes, whose expression results in cell death in the presence of specific pro-drugs. We show the efficacy of this system at enriching for ß cells and eliminating tumorigenic ones both in vitro and in vivo. Our approach is innovative inasmuch as it allows for the preservation of the desired cells while eliminating those with the potential to develop teratomas.

Long-term plasma exchange as maintenance therapy for cerebellar-type Hashimoto's encephalopathy, a case report.

Hashimoto's encephalopathy (HE) is a presumed autoimmune disorder associated with anti-thyroid autoantibodies and signs and symptoms of encephalopathy. A sub-type of HE is associated with cerebellar dysfunction and ataxia. Immunosuppressive therapy, particularly corticosteroid treatment, is utilized in the majority of cases. Short-term apheresis has been reported with variable patient responses. Here we report the case of a 72 year-old female with an ∼15 year history of cerebellar type HE that had profound improvement in symptoms after long-term apheresis treatment over an ∼2 year period. Following an induction phase, twice-weekly maintenance apheresis of 1 plasma volume reversed long-standing severe gait ataxia that had required a walker, as well as mild cognitive symptoms. This paralleled reductions in anti-thyroid antibody levels. Holidays from apheresis lasting several weeks and/or reductions in maintenance apheresis frequency to once per-week resulted in re-expression of ataxia and cognitive impairments along with a rise in anti-thyroid antibody levels. An apheresis dose-effect was observed whereby parallel rise and fall in both symptomatology and antibody levels would mirror duration between apheresis intervals. To our knowledge, this is the first report of profound therapeutic benefit and a dose-response relationship to long-term apheresis in cerebellar-type HE. This case suggests that maintenance apheresis be considered in responsive patients, particularly in those with contraindications to medical immunosuppression.

Safety analysis of apixaban versus warfarin in patients with advanced kidney disease.

Anticoagulation in patients with advanced kidney disease, defined as those with an eGFR < 25 mL/min, including patients with end-stage renal disease on hemodialysis, remains an area of controversy and debate. Due to safety concerns regarding the increased risk for bleeding in this population, these patients have been excluded from all large-scale, randomized controlled trials to date. Warfarin and apixaban are both FDA-approved for use in this population and although warfarin remains the anticoagulant of choice, apixaban use is steadily increasing. This review combines relevant literature to better understand the risk versus benefit of anticoagulation in patients with severe kidney disease as well as the safety of apixaban versus warfarin in this population. High rates of bleed were found among both anticoagulants in those with severe kidney disease, suggesting that the risk for bleed associated with anticoagulation may not outweigh the benefit of treatment. Apixaban was found to be superior in rates of major bleed in those with ESRD on HD and may be superior to warfarin in those with an eGFR < 25 mL/min. However, large-scale, randomized clinical trials are needed to validate these results. With the continued development of novel agents there may be superior alternatives to apixaban and warfarin in those with severe kidney disease in the future.

Síndrome de Burnout y satisfacción laboral en enfermeras(os) de Centro Quirúrgico del Hospital III Emergencias Grau - EsSalud 2015 / Burnout syndrome and job satisfaction in the nurses of the Surgical Center at the Hospital III Emergencies Grau - EsSalud 2015

La presente investigación sobre "Síndrome de Burnout y de Satisfacción Laboral en enfermeras(os) de Centro Quirúrgico del Hospital III Emergencias Grau. Lima - Perú 2015" es importante ya que influyen en su calidad de vida, productividad y desempeño laboral. Objetivo: Determinar el nivel de síndrome de Burnout y de satisfacción laboral presentes en enfermeras(os) de Centro Quirúrgico del Hospital III Emergencias Grau EsSalud. Material y Método: estudio aplicativo, cuantitativo, descriptivo, de corte transversal; mediante encuesta se aplicó el inventario de Burnout de Maslach y la escala de Satisfacción Laboral de Sonia Palma Carrillo, en 22 enfermeras. Resultados: del 100 por ciento (22) enfermeras(os), 59 por ciento (13) presentan Síndrome de Burnout medio en las tres dimensiones, 77 por ciento en realización personal, 68 por ciento en agotamiento emocional y 63 por ciento en despersonalización; Burnout alto en 18 por ciento (4) y bajo en 23 por ciento (5). En satisfacción laboral 36 por ciento (8) tienen satisfacción media, 32 por ciento (7) baja y 32 por ciento (7) alta; En satisfacción alta destaca desarrollo personal 77 por ciento, desempeño de tareas 67 por ciento. En satisfacción media relación con autoridades 67 por ciento, relaciones sociales 63 por ciento y políticas administrativas 50 por ciento; y en Satisfacción baja, condiciones físicas y materiales 72 por ciento y beneficios laborales y remunerativos 65 por ciento. Conclusiones: La mayoría de enfermeras(os) presenta un nivel medio de Síndrome de Burnout, sobre todo en realización personal. Un nivel medio de satisfacción laboral, siendo alto en desarrollo personal y desempeño de tareas; nivel medio en relación con autoridades, relaciones sociales y políticas administrativas; nivel bajo en condiciones físicas y materiales, y beneficios laborales y remunerativos.

The present research on "Burnout syndrome and job satisfaction in the nurses of Surgical Center of the Hospital III Emergencies Grau. Lima Peru. 2015" is important because it influences their quality of life, productivity and job performance. Objective: To determine the level of burnout syndrome and job satisfaction of nurses in Surgical Center of the Hospital III Emergencies Grau. Material and method: applicative, quantitative, descriptive and cross-sectional study; survey by the Maslach Burnout Inventory and Job Satisfaction Scale Sonia Palma Carrillo, 22 nurses applied. Results: 100 per cent (22) Nurses, 59 per cent (13) have average Burnout syndrome level in three dimensions, 77 per cent in personal accomplishment, emotional exhaustion at 68 per cent and 63 per cent in depersonalization; High burnout in 18 per cent (4) and low level in 23 per cent (5). Job satisfaction in 36 per cent (8) have average satisfaction, 32 per cent (7) down and 32 per cent (7) high; In high satisfaction it emphasizes personal development 77 per cent, 67 per cent performing tasks. On average satisfaction regarding authorities 67 per cent, social relations 63 per cent and administrative policies 50 per cent; and low satisfaction, physical and material conditions and 72 per cent and remunerative employment benefits 65 per cent. Conclusions: The majority of nurses has an average level of burnout syndrome, especially in personal fulfillment. An average level of job satisfaction remains high on staff development and performance of tasks; means in relation to authorities, social relations and administrative policies; low physical conditions and materials, and labor benefits and remunerative.