Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Improving early cholecystectomy rate in acute cholecystitis with an evidence-based local multidisciplinary protocol and a surgical audit: single-center experience through an Acute Care Surgery Division.

PURPOSE: To analyze if, after implementation of an evidence-based local multidisciplinary protocol for acute cholecystitis (AC), an intermediate surgical audit could improve early cholecystectomy (EC) rate and other therapeutic indicators. METHODS: Longitudinal cohort study at a tertiary center. The local protocol, promoted, created, and periodically revised by the Acute Care Surgery Unit (ACSu) was updated and approved on March 2019. A specific registry was prospectively fulfilled with demographics, comorbidity, type of presentation, diagnostic items, therapeutic decision, and clinical course, considering both non-operative management (NOM) or cholecystectomy, early and delayed (EC and DC). Phase 1: April 2019-April 2021. A critical analysis and a surgical audit with the participation of all the involved Departments were then performed, especially focusing on improving global EC rate, considered primary outcome. Phase 2: May 2021-May 2023. Software SPSS 23.0 was used to compare data between phases. RESULTS: Initial EC rate was significantly higher on Phase 2 (39.3%vs52.5%, p < 0.004), as a significantly inferior rate of patients were initially bailed out from EC to NOM because of comorbidity (14.4%vs8%, p < 0.02) and grade II with severe inflammatory signs (7%vs3%, p < 0.04). A higher percentage of patients was recovered for EC after an initial decision of NOM on Phase 2, but without reaching statistical significance (21.8%vs29.2%, n.s.). Global EC rate significantly increased between phases (52.5%vs66.3%, p < 0.002) without increasing morbidity and mortality. A significant minor percentage of elective cholecystectomies after AC episodes had to be performed on Phase 2 (14%vs6.7%, p < 0.009). Complex EC and those indicated after readmission or NOM failure were usually performed by the ACSu staff. CONCLUSION: To adequately follow up the implementation of a local protocol for AC healthcare, registering and periodically analyzing data allow to perform intermediate surgical audits, useful to improve therapeutic indicators, especially EC rate. AC constitutes an ideal model to work with an ACSu.

El papel de la PET/TC con 2-[18F]FDG en la enfermedad de Erdheim-Chester / The role of 2-[18F]FDG PET/CT in Erdheim-Chester disease

Objetivo Analizar la distribución corporal de la enfermedad Erdheim-Chester (ECD) y determinar la utilidad de la 2-[18F]FDG-PET/TC frente a otras técnicas de imagen. Asimismo, evaluar la agresividad y la extensión de la enfermedad según la presencia/ausencia de mutación BRAFV600E. Material y métodos Se revisaron las 2-[18F]FDG-PET/TC de todos los pacientes diagnosticados con ECD entre 2008 y 2021: en total, 19 pacientes. Los territorios afectados se clasificaron como detectables por PET/TC o detectables solamente por otras técnicas de imagen (gammagrafía ósea, TC con contraste yodado o RM). Se realizó análisis descriptivo y correlación de la mutación BRAF con los órganos afectados y SUVmáx mediante la prueba t de Student. Resultados De los 19 pacientes (14 hombres; edad media 60,3años), 11 presentaban la mutación BRAFV600E. Se detectaron un total de 127 territorios (64 órgano-sistemas) afectados utilizando las diferentes modalidades de imagen, de los cuales 112 fueron detectados por la PET/TC y 15 territorios adicionales fueron identificados únicamente por la RM cerebral y cardiaca. La presencia de mutación BRAFV600E se asoció con mayor afectación orgánica (p<0,05), sin diferencias en el SUVmáx (p>0,05). Conclusión La 2-[18F]FDG-PET/TC es una prueba de alto rendimiento diagnóstico en pacientes con ECD, detectando la mayoría de los territorios afectados. La RM fue la única prueba de imagen con hallazgos adicionales en territorios con alta captación fisiológica de 2-[18F]FDG (cerebral y cardíaca). La presencia de mutación del BRAFV600E se correlacionó con mayor extensión de la enfermedad (AU)

Objective To analyze the body distribution of Erdheim-Chester disease (ECD) and determine the utility of 2-[18F]FDG PET/CT compared to other imaging techniques. Additionally, to assess the aggressiveness and extent of the disease based on the presence/absence of the BRAFV600E mutation. Materials and methods The 2-[18F]FDG PET/CT scans of all patients diagnosed with ECD between 2008 and 2021 were reviewed, including 19 patients. The affected territories were classified as detectable by PET/CT or detectable only by other imaging techniques (bone scintigraphy, contrast-enhanced CT, or MRI). Descriptive analysis and correlation of the BRAF mutation with the affected organs and maximum SUV were performed using the Student's t-test. Results Out of the 19 patients (14 males; mean age 60.3years), 11 had the BRAFV600E mutation. A total of 127 territories (64 organ-systems) affected were identified using different imaging modalities, of which 112 were detected by PET/CT, and an additional 15 territories were solely identified by cerebral and cardiac MRI. The presence of BRAFV600E mutation was associated with greater organ involvement (P<.05) without differences in SUVmax (P>.05). Conclusion 2-[18F]FDG PET/CT is a highly effective diagnostic tool in patients with ECD, detecting the majority of affected territories. MRI was the only imaging modality with additional findings in territories showing high physiological uptake of 2-[18F]FDG (cerebral and cardiac). The presence of the BRAFV600E mutation correlated with a higher extent of the disease (AU)

The role of 2-[18F]FDG PET/CT in Erdheim-Chester disease.

OBJECTIVE: To analyze the body distribution of Erdheim-Chester disease (ECD) and determine the utility of 2-[18 F]FDG PET/CT compared to other imaging techniques. Additionally, to assess the aggressiveness and extent of the disease based on the presence/absence of the BRAFV600E mutation. MATERIALS AND METHODS: The 2-[18F]FDG-PET/CT scans of all patients diagnosed with ECD between 2008 and 2021 were reviewed, including 19 patients. The affected territories were classified as detectable by PET/CT or detectable only by other imaging techniques (bone scintigraphy, contrast-enhanced CT, or MRI). Descriptive analysis and correlation of the BRAF mutation with the affected organs and maximum SUV were performed using the Student's t-test. RESULTS: Out of the 19 patients (14 males; mean age 60.3 years), 11 had the BRAFV600E mutation. A total of 127 territories (64 organ-systems) affected were identified using different imaging modalities, of which 112 were detected by PET/CT, and an additional 15 territories were solely identified by cerebral and cardiac MRI. The presence of BRAFV600E mutation was associated with greater organ involvement (p < 0.05) without differences in SUVmax (p > 0.05). CONCLUSION: 2-[18F]FDG PET/CT is a highly effective diagnostic tool in patients with ECD, detecting the majority of affected territories. MRI was the only imaging modality with additional findings in territories showing high physiological uptake of 2-[18F]FDG (cerebral and cardiac). The presence of the BRAFV600E mutation correlated with a higher extent of the disease.

Immunoglobulins in systemic sclerosis management. A large multicenter experience.

OBJECTIVE: To analyze the effectiveness and safety of intravenous immunoglobulin (IVIG) given in routine care to patients with systemic sclerosis (SSc). METHODS: A retrospective multicenter observational study was conducted in SSc patients treated with IVIG. We collected data on epidemiological parameters and clinical outcomes. Firstly, we assessed changes in organ manifestations during IVIG treatment. Secondly, we analyzed the frequency of adverse effects. The following parameters were collected from baseline to the last follow-up: the patient's weight, modified Rodnan Skin Score (mRSS), modified manual muscle strength scale (MRC), laboratory test(creatine kinase(CK), hemoglobin and protein levels), The University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 (UCLA GIT 2.0) questionnaire, pulmonary function tests, and echocardiography. RESULTS: Data were collected on 78 patients (82% females; 59% with diffuse SSc). Inflammatory idiopathic myopathy was the most frequent concomitant overlap disease (41%). The time since Raynaud's phenomenon and SSc onset were 8.8 ± 18 and 6.2 ± 6.7 years respectively. The most frequent IVIG indication was myositis (38/78), followed by gastrointestinal (27/78) and cutaneous (17/78) involvement. The median number of cycles given were 5. 54, 53 and 9 patients have been treated previously with glucocorticoids, synthetic disease-modifying antirheumatic drugs and biologic therapies respectively. After IVIG use we found significant improvements in muscular involvement (MRC ≥ 3/5 92% IVIG, p = 0.001 and CK levels from 1149 ± 2026 UI to 217 ± 224 UI, p = 0.02), mRSS (15 ± 12.4 to 13 ± 12.5, p = 0.015) and improvement in total score of UCLA GIT 2.0 (p = 0.05). None Anti-RNA polymerase III patients showed an adequate response in gastrointestinal involvement (0/7) in comparison with other antibodies (0 vs. 25, p = 0,039). Cardiorespiratory involvement remained stable. A total of 12 adverse events were reported with only one withdrawn due to serious adverse effect. CONCLUSIONS: this study suggest that IVIG may improve myositis, gastrointestinal and skin involvement in SSc patients treated in routine care and seems to have a good safety profile.

Impact of previous glucocorticoid therapy on diagnostic accuracy of [18F] FDG PET-CT in giant cell arteritis.

OBJECTIVE: To evaluate the impact of prior glucocorticoid (GC) treatment on the diagnostic accuracy of 18F-FDG PET-CT in giant cell arteritis (GCA). METHODS: Retrospective study of a consecutive cohort of 85 patients with proven GCA who received high-dose GC before PET-CT. RESULTS: Thirty-nine patients previously treated with methylprednisolone (MP) boluses, of whom 37% were PET-CT (uptakes grade 3 or 2) positive. The positivity rate was 80% with MP doses of 125 mg, 33% with 250 or 500 mg, and 0% with doses of 1 g.  If we also classify as positive those cases with a grade 1 uptake (with a circumferencial uptake and smooth linear or long segmental pattern, possibly indicative of "apparently inactive" vasculitis), the positivity rate increases to 62% (100%, 50-60%, and 33% for the different MP doses, respectively). In patients with new-onset GCA treated with high-dose oral GC, PET-CT positivity was 54.5% in patients treated for less than two weeks, 38.5% in those treated for 2 to 4 weeks, and 25% in those treated for 4 to 6 weeks (increasing to 91%, 77%, and 50%, respectively, if we include cases with grade 1 uptake and these characteristics). In patients with relapsing/refractory GCA, or who developed GCA having a prior history of PMR, PET-CT positivity reached 54% despite long-term treatment with low-to-moderate doses of GC (68% including cases with a grade 1 uptake). CONCLUSION: A late 18F-FDG PET-CT (beyond the first 10 days of treatment) can also be informative in a considerable percentage of cases.

Perioperative and oncologic outcomes of interval colectomy performed by acute care surgeons after stenting as a bridge to surgery for left-sided malignant colonic obstruction are non-inferior to the outcomes of colorectal surgeons in the elective setting: single center experience.

PURPOSE: To analyze if perioperative and oncologic outcomes with stenting as a bridge to surgery (SEMS-BS) and interval colectomy performed by acute care surgeons for left-sided occlusive colonic neoplasms (LSCON) are non-inferior to those obtained by colorectal surgeons for non-occlusive tumors of the same location in the full-elective context. METHODS: From January 2011 to January 2021, patients with LSCON at University Regional Hospital in Málaga (Spain) were directed to a SEMS-BS strategy with an interval colectomy performed by acute care surgeons and included in the study group (SEMS-BS). The control group was formed with patients from the Colorectal Division elective surgical activity dataset, matching by ASA, stage, location and year of surgery on a ratio 1:2. Stages IV or palliative stenting were excluded. Software SPSS 23.0 was used to analyze perioperative and oncologic (defined by overall -OS- and disease free -DFS-survival) outcomes. RESULTS: SEMS-BS and control group included 56 and 98 patients, respectively. In SEMS-BS group, rates of technical/clinical failure and perforation were 5.35% (3/56), 3.57% (2/56) and 3.57% (2/56). Surgery was performed with a median interval time of 11 days (9-16). No differences between groups were observed in perioperative outcomes (laparoscopic approach, primary anastomosis rate, morbidity or mortality). As well, no statistically significant differences were observed in OS and DFS between groups, both compared globally (OS:p < 0.94; DFS:p < 0.67, respectively) or by stages I-II (OS:p < 0.78; DFS:p < 0.17) and III (OS:p < 0.86; DFS:p < 0.70). CONCLUSION: Perioperative and oncologic outcomes of a strategy with SEMS-BS for LSCON are non-inferior to those obtained in the elective setting for non-occlusive neoplasms in the same location. Technical and oncologic safety of interval colectomy performed on a semi-scheduled situation by acute care surgeons is absolutely warranted.

Teaching surgery novices and trainees advanced laparoscopic suturing: a trial and tribulations.

INTRODUCTION: The benefits of minimally invasive surgery are numerous; however, considerable variability exists in its application and there is a lack of standardized training for important advanced skills. Our goal was to determine whether participation in an advanced laparoscopic curriculum (ALC) results in improved laparoscopic suturing skills. METHODS AND PROCEDURES: Study design was a prospective, randomized controlled trial. Surgery novices and trainees underwent baseline FLS training and were pre-tested on bench models. Participants were stratified by pre-test score and randomized to undergo either further FLS training (control group) or ALC training (intervention group). All were post-tested on the same bench model. Tests for differences between post-test scores of cohorts were performed using least squared means. Multivariable regression identified predictors of post-test score, and Wilcoxon rank sum test assessed for differences in confidence improvement in laparoscopic suturing ability between groups. RESULTS: Between November 2018 and May 2019, 25 participants completed the study (16 females; 9 males). After adjustment for relevant variables, participants randomized to the ALC group had significantly higher post-test scores than those undergoing FLS training alone (mean score 90.50 versus 82.99, p = 0.001). The only demographic or other variables found to predict post-test score include level of training (p = 0.049) and reported years of video gaming (p = 0.034). There was no difference in confidence improvement between groups. CONCLUSIONS: Training using the ALC as opposed to basic laparoscopic skills training only is associated with superior advanced laparoscopic suturing performance without affecting improvement in reported confidence levels. Performance on advanced laparoscopic suturing tasks may be predicted by lifetime cumulative video gaming history and year of training but does not appear to be associated with other factors previously studied in relation to basic laparoscopic skills, such as surgical career aspiration or musical ability.

A prospective study of lung disease in a cohort of early rheumatoid arthritis patients.

Lung disease is common in patients with rheumatoid arthritis (RA). The onset of lung involvement in RA is not well known. The objective is to describe the features and evolution of lung involvement in early RA, its relationship with disease activity parameters, smoking and treatments. Consecutive patients with early RA without respiratory symptoms were included and tracked for 5 years. Lung assessment included clinical, radiological and pulmonary function tests at diagnosis and during follow-up. Peripheral blood parameters (erythrocyte sedimentation rate, C reactive protein, rheumatoid factor and anti-citrullinated peptide autoantibodies) and scales of articular involvement, such as DAS28-CRP, were evaluated. 40 patients were included and 32 completed the 5-year follow up. 13 patients presented lung involvement in the initial 5 years after RA diagnosis, 3 of them interstitial lung disease. Significant decrease of diffusion lung transfer capacity of carbon monoxide over time was observed in six patients, 2 of them developed interstitial lung disease. DLCO decrease was correlated with higher values of CRP and ESR at diagnosis. Methotrexate was not associated with DLCO deterioration or lung disease development. Subclinical progressive lung disease correlates with RA activity parameters. Smoking status and methotrexate were not associated with development or progression of lung disease.

Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry).

BACKGROUND: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. OBJECTIVES: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. METHODS: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. RESULTS: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). CONCLUSION: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

Transplant Outcomes of Donation After Circulatory Death Livers Recovered With Versus Without Premortem Heparin Administration.

Premortem heparin administration during donation after circulatory death (DCD) organ recovery is thought to optimize liver perfusion. However, premortem heparinization is not universally practiced in the United States and limited data exist regarding its utility. US registry data were accessed between January 1, 2003, and March 10, 2017, and 2 cohorts were ascertained: (1) DCD donor livers recovered for transplantation (n = 5495) and (2) liver-only adult transplant recipients of DCD livers (n = 3754). Exclusions were donor unknown heparin status (n = 40), positive donor hepatitis B surface antigen (n = 4) and hepatitis C virus (n = 120) serologies, and for the outcomes analysis, livers placed outside the United States (n = 10). Discard rates and graft outcomes were examined from cohorts 1 and 2, respectively. Of 5495 DCD livers recovered for transplant, 589 (10.7%) donors did not receive premortem heparin (no heparin) and the remaining 4906 (89.3%) received heparin (heparin). Liver discard was similar between the no heparin (30.6%) and heparin groups (30.8%; P = 0.90). Heparin status was not associated with liver discard on multivariate analysis (adjusted odds ratio, 0.97; 95% confidence interval [CI], 0.80-1.18 P = 0.76). The cumulative probability of overall graft survival was lower in the no heparin group relative to the heparin group (P < 0.05), and this finding persisted on multivariate analysis. No heparin group transplants had an 18% higher hazard of overall graft failure compared with those that received heparin (adjusted hazard ratio, 1.18; 95% CI, 1.01-1.38; P < 0.05). In conclusion, organ recovery heparin administration status was not associated with liver discard. Failure to pretreat organ donors with premortem heparin correlates with worse liver transplant graft survival compared with heparin-treated livers.

Outcomes of DCD kidneys recovered for transplantation with versus without pre-mortem heparin administration.

BACKGROUND: Pre-mortem heparin administration during donation after circulatory death (DCD) organ recovery may be particularly important to improve perfusion and prevent graft thrombosis. However, pre-mortem heparin administration is not universally practiced in the US and scarce data exist regarding its efficacy. METHODS: Using a national transplant registry data, we identified DCD kidneys recovered for transplantation from January 1, 2003, to March 10, 2017, and examined discard and outcomes after transplantation using bivariate and multivariable analyses. Organs with unknown or missing donor heparin status (n = 193), seropositive HIV (n = 10), HTLV (n = 33), hepatitis B (n = 26), or hepatitis C (n = 648) were excluded. RESULTS: Of 24 861 DCD kidneys recovered with (n = 22 557) or without pre-mortem heparin administration (n = 2304), discard occurred in 19.1% and 20.8%, respectively (P = 0.05). On multivariate analysis, heparin use was not associated with discard (aOR 1.02, 95% CI 0.89-1.17, P = 0.820). Overall graft survival of no-heparin (n = 1791) vs heparin groups (n = 17 968) was similar on univariate and multivariate analysis (aHR 0.98, 95% CI 0.87-1.09, P = 0.640). CONCLUSION: DCD kidneys from donors that have not received pre-mortem heparin administration have acceptable transplant outcomes and are not associated with discard.

Donation After Cardiac Death in Liver Transplantation: An Additional Source of Organs With Similar Results to Donation After Brain Death.

BACKGROUND: As new sources of organs are needed, liver transplantation using donors after cardiac death (DCD) is progressively increasing, but outcomes with this method are still questioned. This study was accomplished to verify that DCD outcomes are comparable to those seen in donation after brain death (DBD). METHODS: This was a prospective cohort study including 100 liver transplantation performed between 2014 and 2017, divided according to donor type in 75 DBD and 25 DCD. RESULTS: DCD donors were younger (mean age: DCD 56 years, DBD 59 years; P = .009). Mean Modified End-stage Liver Disease (MELD) score was lower for DCD (DCD 16, DBD 19; P < .001). No differences were found regarding ischemia times and development of postreperfusion syndrome or coagulopathy. Primary graft dysfunction was more frequent in DCD (60%, DCD 29.3%; P = .006). Rates of primary graft nonfunction (DCD 0%, DBD 1.3%; P = .562) and acute rejection (DCD 20%, DBD 16.4%; P = .685) were similar. Acute kidney injury occurred more often in DBD (DCD 32%, DBD 12%; P = .051). Length of stay was comparable. Rates of biliary complications (DCD 20%, DBD 26.7%; P = .505) were similar, unlike ischemic cholangiopathy (DCD 12%, DBD 1.3%; P = .018). Retransplantation rates were also similar (DCD 8%, DBD 4%; P = .427) as was survival rate after 3 years (DCD 84%, DBD 86.7%; P = .739). CONCLUSION: DCD represents an additional graft source with results that are encouraging and may be comparable to DBD with a careful donor and recipient selection.

Rheumatic immune-related adverse events in patients on anti-PD-1 inhibitors: Fasciitis with myositis syndrome as a new complication of immunotherapy.

OBJECTIVE: To evaluate the prevalence and type of rheumatic immune-related adverse events (IRAEs) in patients receiving programmed cell death protein-1 (PD-1) inhibitors. METHODS: This is a single-center prospective observational study, including all cancer patients receiving PD-1 inhibitors between January 2016 and January 2018. RESULTS: During the period analyzed, we evaluated a total of 11 patients. No patient had pre-existing rheumatic or autoimmune disease. In this period, a total of 220 patients were treated with PD1 inhibitors in our center; therefore, the estimated minimum prevalence of rheumatic IRAEs related to these therapies in our population was 5%. The rheumatic IRAEs evaluated included 5 cases of oligo- or polyarthritis, 1 with a polymialgia rheumatica-type syndrome, 2 cases of immunotherapy-induced sicca syndrome, 2 patients who presented symptomatic inflammatory myositis with fasciitis in lower extremities, and 1 patient with a paraneoplastic acral vascular syndrome. The median time to IRAE after anti-PD1 exposure was 8 weeks (range: 2-24). In 5 patients, immunotherapy was discontinued (due to the adverse effect in three and cancer progression in two). In general terms the symptoms resolved completely with symptomatic treatment. Disease-modifying antirheumatic drugs were needed for 2 patients. CONCLUSION: Rheumatic IRAEs should be kept in mind during the follow-up and evaluation of patients treated with PD-1 inhibitors. The concomitant development of symptomatic inflammatory myositis with fasciitis in lower extremities appears to be a new adverse effect of anti-PD-1 immunotherapy. Additional studies are needed to determine how to adequately control and manage these complications.

Intravenous pulses of methylprednisolone to treat flares of immune-mediated diseases: how much, how long?

Introduction Glucocorticoids are widely used in the treatment of immune-mediated diseases. Despite their widespread use, details on dosing, effectiveness and adverse effects are yet to be determined. Objective To know the current use of methylprednisolone (MTP) in the management of immune-mediated conditions, evaluating the relationship among doses, therapeutic response and adverse effects. Methodology A multicenter retrospective cohort study was designed, including patients who received intravenous pulses of MTP between 1 January 2013 and 12 December 2015 in three different hospitals in Uruguay. The patients included received MTP to treat systemic autoimmune diseases (SADs), hematological, nephrological and neurologic diseases and others. The following variables were analyzed: age, gender, MTP cumulative dose, duration of treatment, clinical response (complete, partial and no response) and adverse effects. Results In total, 164 cases were identified, of which 118 (72%) were female. The median age was 48.4 (SD: 18) years. The indications for MTP included: neuroimmune-mediated 92 (56.1%), SADs 29 (17.5%), hematological 15 (9.1%), nephrological 12 (7.3%) and others 16 (9.9%). The median dose to achieve complete response was 3.2 g (SD: 1.5); the median dose to accomplish a partial response was 3.5 g (SD: 1.25); the median dose for non-responders was 3.3 g (SD 1.2) ( p > 0.05). The median dose in those patients with adverse effects was 3.4 g (SD 1.5) and the median dose for those who did not experience adverse effects was 3.3 g (SD: 1.3) ( p > 0.05). The most frequent adverse effects were infectious (22/164, 13.4%). Diabetics were found to have the highest incidence of adverse effects (13/16, 81%) in comparison to non-diabetics, p < 0.05. Discussion Our study suggests a wide range of doses and duration of treatments with MTP. No major associations were found between clinical response and the use of high MTP doses, but the latter was associated with a large proportion of severe infections. No severe infections were identified with MTP doses lower than 1.5 g. The diabetic population is known to be at risk of experiencing varied adverse effects to MTP. These observations reinforce the need for protocolized use of MTP in order to achieve a better relationship among doses, effectiveness and safety profile.

Hard-to-place kidney offers: Donor- and system-level predictors of discard.

Understanding risk factors for deceased-donor kidney nontransplantation is important since discard rates remain high. We analyzed DonorNet® data of consecutive deceased-donor nonmandatory share primary kidney-only offers to adult candidates at our center and beyond between July 1, 2015 and March 31, 2016 for donor- and system-level risk factors of discard, defined as nontransplantation at our or subsequent transplant centers. Exclusions were hepatitis C virus/hepatitis B virus core antibody status, blood type AB, and donor <1 year based on low candidate waitlist size. Of 456 individual kidney offers, from 296 donors, 73% were discarded. Most were national (93%) offers from Kidney Donor Profile Index 35-85% (n = 233) or >85% (n = 208) donors late in the allocation sequence with prior refusals logged for numerous candidates. On multivariate regression, factors significantly associated with discard were donor cerebrovascular accident (adjusted odds ratio [aOR]: 3.32), cancer transmission concern (aOR: 6.5), renal artery luminal compromise (aOR: 3.97), biopsy score ≥3 (aOR: 5.09), 2-hour pump resistive index >0.4 (aOR: 3.27), absence of pump (aOR: 2.58), nonspecific kidney abnormality (aOR: 2.76), increasing offer cold ischemia time category 11-15, 16-20, and >21 hours (aOR: 2.07, 2.33, 2.82), nighttime notification (aOR: 2.19), and neither kidney placed at time of offer (aOR: 2.74). Many traditional determinants of discard lack discriminatory value when granular factors are assessed. System-level factors also influence discard and warrant further study.

Combined Flush With Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Solutions in Liver Transplantation: Preliminary Results.

INTRODUCTION: Ischemia reperfusion injury (IRI) is the main cause of early allograft dysfunction (EAD) and subsequent primary allograft failure (PAF). OBJECTIVES: The purpose of this study is to compare IRI, EAD, and PAF in liver transplantation in a cohort of patients perfused with histidine-tryptophan-ketoglutarate (HTK) solution and University of Wisconsin (UW) solution versus HTK alone. METHODS: A randomized trial was performed to compare outcomes in liver recipients who underwent transplantation surgery in the University Regional Hospital of Malaga, Spain. Forty patients were randomized to two groups. Primary endpoints included IRI, EAD, PAF, re-intervention, acute cellular rejection, retransplantation, arterial complications, and biliary complications at postoperative day 90. RESULTS: Postoperative glutamic oxaloacetic transaminase (1869.15 ± 1559.75 UI/L vs. 953.15 ± 777.27 UI/L; P = .004) and glutamic pyruvic transaminase (1333.60 ± 1115.49 U/L vs. 721.70 ± 725.02 U/L; P = .023) were significantly higher in patients perfused with HTK alone. A clear tendency was observed in recipients perfused with HTK alone to present moderate to severe IRI (7 patients in the HTK + UW solution group vs. 15 patients in the HTK-alone solution group; P = .06), EAD (0 patients in the HTK + UW solution group vs. 0 patients in the HTK-alone solution group; P = .76), and PAF (3 patients in the HTK + UW solution group vs. 8 patients in the HTK-alone solution group; P = .15). CONCLUSIONS: Initial perfusion with HTK solution followed by UW solution in liver transplantation improves early liver function as compared to perfusion with HTK alone.

Benefits of multimodal enhanced recovery pathway in patients undergoing kidney transplantation.

BACKGROUND: Use of enhanced recovery after surgery (ERAS) pathways to accelerate functional recovery and reduce length of stay (LOS) has rarely been investigated in kidney transplantation (KTX). MATERIALS AND METHODS: Consecutive adult isolated KTXs between July 2015 and July 2016 (ERAS, n = 139) were compared with a historical cohort between January 2014 and July 2015 (HISTORIC, n = 95). RESULTS: Enhanced recovery after surgery recipients were significantly more likely to receive kidneys that were non-local (56.1% vs 4.2%), higher Kidney Donor Profile Index (36-85, 58.4% vs 45.2%; >85, 15.2% vs 10.7%), cold ischemia time ≥30 h (62.4% vs 4.7%), induced with antithymocyte globulin (97.1% vs 87.4%), and to develop delayed graft function (46.4% vs 25.0%). LOS was shorter by 1 day among ERAS (mean 4.59) compared to HISTORIC patients (mean 5.65) predominantly due to a shift in discharges within 3 days (32.4% vs 4.2%); 30-day readmission to the hospital (27.3% vs 27.4%) or emergency room visit (9.4% vs 7.4%) was similar. There was one 30-day death in the ERAS group and none in the HISTORIC group. Return to bowel function and early meal consumption were significantly associated with ERAS, however, with somewhat higher diarrhea and emesis rates. CONCLUSION: ERAS following KTX correlated with lower LOS without change in readmissions or ER visits despite higher delayed graft function rates.