Biomarkers of Fibrosis in Patients with COVID-19 One Year After Hospital Discharge: A Prospective Cohort Study.

Beyond the acute infection of coronavirus disease (COVID-19), concern has arisen about long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of our study was to analyze if there is any biomarker of fibrogenesis in patients with COVID-19 pneumonia capable of predicting post-COVID-19 pulmonary sequelae. We conducted a multicenter, prospective, observational cohort study of patients admitted to a hospital with bilateral COVID-19 pneumonia. We classified patients into two groups according to severity, and blood sampling to measure matrix metalloproteinase 1 (MMP-1), MMP-7, periostin, and VEGF and respiratory function tests and high-resolution computed tomography were performed at 2 and 12 months after hospital discharge. A total of 135 patients were evaluated at 12 months. Their median age was 61 (interquartile range, 19) years, and 58.5% were men. We found between-group differences in age, radiological involvement, length of hospital stay, and inflammatory laboratory parameters. Differences were found between 2 and 12 months in all functional tests, including improvements in predicted forced vital capacity (98.0% vs. 103.9%; P = 0.001) and DlCO <80% (60.9% vs. 39.7%; P = 0.001). At 12 months, 63% of patients had complete high-resolution computed tomography resolution, but fibrotic changes persisted in 29.4%. Biomarker analysis demonstrated differences at 2 months in periostin (0.8893 vs. 1.437 ng/ml; P < 0.001) and MMP-7 (8.7249 vs. 15.2181 ng/ml; P < 0.001). No differences were found at 12 months. In multivariable analysis, only 2-month periostin was associated with 12-month fibrotic changes (odds ratio, 1.0013; 95% confidence interval, 1.0006-1.00231; P = 0.003) and 12-month DlCO impairment (odds ratio, 1.0006; 95% confidence interval, 1.0000-1.0013; P = 0.047). Our data suggest that early periostin postdischarge could predict the presence of fibrotic pulmonary changes.

Uso y abuso del sulfato de magnesio en las crisis asmáticas / Use and abuse of magnesium sulfate in asthmatic exacerbations

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Hospitalizations for Alcohol and Opioid Use Disorders in Older Adults: Trends, Comorbidities, and Differences by Gender, Race, and Ethnicity.

Background: The prevalence of substance use disorders (SUDs) among adults ages 65 and older has been increasing at a notably high rate in recent years, yet little information exists on hospitalizations for SUDs among this age group. In this study we examined trends in hospitalizations for alcohol use disorders (AUDs) and opioid use disorders (OUDs) among adults 65 and older in the United States, including differences by gender and race/ethnicity. Methods: We used Medicare claims data for years 2007-2014 from beneficiaries ages 65 and older. We abstracted hospitalization records with an ICD-9 diagnostic code for an AUD or OUD. Hospitalization rates were calculated using population estimates from the United States Census. We examined trends in quarterly hospitalization rates for hospitalizations with AUD/OUD as primary diagnoses, and separately for those with these disorders as secondary diagnoses. We also examined comorbidities for those with a primary diagnosis of AUD/OUD. Analyses were conducted for all hospitalizations with AUD/OUD diagnoses, and separately by gender and race/ethnicity. Results: Between the last quarter of 2007 and the third quarter of 2014, AUD hospitalization rates increased from 485 to 579 per million (19%), and OUD hospitalization rates from 46 to 101 per million (120%) and varied by gender (for AUD) and race/ethnicity (for both AUD and OUD). Hospitalization rates were particularly high for Black older adults, as was the increase in hospitalization rates. The increase in hospitalization rates was substantially higher for hospitalizations with AUD (84%) and OUD (269%) as secondary diagnoses. Conclusions: Hospitalizations for AUDs and OUDs among older adults increased at an alarming rate during the observation period, and disparities existed in hospitalization rates for these conditions. Interventions focusing on the needs of older adults with AUD and/or OUD are needed, particularly to address the needs of a growing racially/ethnically diverse older adult population.

Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study.

BACKGROUND: In May, 2022, several European countries reported autochthonous cases of monkeypox, which rapidly spread globally. Early reports suggest atypical presentations. We aimed to investigate clinical and virological characteristics of cases of human monkeypox in Spain. METHODS: This multicentre, prospective, observational cohort study was done in three sexual health clinics in Madrid and Barcelona, Spain. We enrolled all consecutive patients with laboratory-confirmed monkeypox from May 11 to June 29, 2022. Participants were offered lesion, anal, and oropharynx swabs for PCR testing. Participant data were collected by means of interviews conducted by dermatologists or specialists in sexually transmitted infections and were recorded using a standard case report form. Outcomes assessed in all participants with a confirmed diagnosis were demographics, smallpox vaccination, HIV status, exposure to someone with monkeypox, travel, mass gathering attendance, risk factors for sexually transmitted infections, sexual behaviour, signs and symptoms on first presentation, virological results at multiple body sites, co-infection with other sexually transmitted pathogens, and clinical outcomes 14 days after the initial presentation. Clinical outcomes were followed up until July 13, 2022. FINDINGS: 181 patients had a confirmed monkeypox diagnosis and were enrolled in the study. 166 (92%) identified as gay men, bisexual men, or other men who have sex with men (MSM) and 15 (8%) identified as heterosexual men or heterosexual women. Median age was 37·0 years (IQR 31·0-42·0). 32 (18%) patients reported previous smallpox vaccination, 72 (40%) were HIV-positive, eight (11%) had a CD4 cell count less than 500 cells per µL, and 31 (17%) were diagnosed with a concurrent sexually transmitted infection. Median incubation was 7·0 days (IQR 5·0-10·0). All participants presented with skin lesions; 141 (78%) participants had lesions in the anogenital region, and 78 (43%) in the oral and perioral region. 70 (39%) participants had complications requiring treatment: 45 (25%) had a proctitis, 19 (10%) had tonsillitis, 15 (8%) had penile oedema, six (3%) an abscess, and eight (4%) had an exanthem. Three (2%) patients required hospital admission. 178 (99%) of 180 swabs from skin lesions collected tested positive, as did 82 (70%) of 117 throat swabs. Viral load was higher in lesion swabs than in pharyngeal specimens (mean cycle threshold value 23 [SD 4] vs 32 [6], absolute difference 9 [95% CI 8-10]; p<0·0001). 108 (65%) of 166 MSM reported anal-receptive sex. MSM who engaged in anal-receptive sex presented with proctitis (41 [38%] of 108 vs four [7%] of 58, absolute difference 31% [95% CI 19-44]; p<0·0001) and systemic symptoms before the rash (67 [62%] vs 16 [28%], absolute difference 34% [28-62]; p<0·0001) more frequently than MSM who did not engage in anal-receptive sex. 18 (95%) of 19 participants with tonsillitis reported practising oral-receptive sex. The median time from onset of lesions to formation of a dry crust was 10 days (IQR 7-13). INTERPRETATION: In our cohort, monkeypox caused genital, perianal, and oral lesions and complications including proctitis and tonsillitis. Because of the variability of presentations, clinicians should have a low threshold for suspicion of monkeypox. Lesion swabs showed the highest viral loads, which, combined with the history of sexual exposure and the distribution of lesions, suggests close contact is probably the dominant transmission route in the current outbreak. FUNDING: None.

COVID negative, lockdown positive: An observational, prospective comparative study about surgery and quarantine among the eldest old / COVID negativo, confinamiento positivo: estudio observacional, prospectivo y comparativo sobre el impacto preoperatorio de la cuarentena entre los pacientes más ancianos

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Lung Function, Radiological Findings and Biomarkers of Fibrogenesis in a Cohort of COVID-19 Patients Six Months After Hospital Discharge / Función pulmonar, hallazgos radiológicos y biomarcadores de la fibrogénesis en una cohorte de pacientes de COVID-19 seis meses después del alta

Introduction Impairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia. Methods COVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits. Results In total, 313, aged 61.12±12.26 years, out of 481 included patients were available. The proportion of patients with DLCO<80% was 54.6% and 47% at 60 and 180 days. Associated factors with diffusion impairment at 6 months were female sex (OR: 2.97, 95%CI 1.74–5.06, p=0.001), age (OR: 1.03, 95% CI: 1.01–1.05, p=0.005), and peak RALE score (OR: 1.22, 95% CI 1.06–1.40, p=0.005). Patients with altered lung diffusion showed higher levels of MMP-7 (11.54±8.96 vs 6.71±4.25, p=0.001), and periostin (1.11±0.07 vs 0.84±0.40, p=0.001). 226 patients underwent CT scan, of whom 149 (66%) had radiological sequelae of COVID-19. In severe patients, 68.35% had ground glass opacities and 38.46% had parenchymal bands. Early fibrotic changes were associated with higher levels of MMP7 (13.20±9.20 vs 7.92±6.32, p=0.001), MMP1 (10.40±8.21 vs 6.97±8.89, p=0.023), and periostin (1.36±0.93 vs 0.87±0.39, p=0.001). Conclusion Almost half of patients with moderate or severe COVID-19 pneumonia had impaired pulmonary diffusion six months after discharge. Severe patients showed fibrotic lesions in CT scan and elevated serum biomarkers involved in pulmonary fibrosis.

Introducción El deterioro de la función pulmonar en las pruebas correspondientes y las alteraciones radiológicas son las preocupaciones principales en los supervivientes de la COVID-19. Nuestro objetivo fue evaluar los parámetros de la función respiratoria, los cambios en la TC de tórax y la correlación con los biomarcadores en sangre periférica involucrados en la fibrosis pulmonar a los 2 y a los 6 meses tras la neumonía por SARS-CoV-2. Métodos El ensayo COVID-FIBROTIC (clinicaltrials.gov NCT04409275) es un estudio de cohortes multicéntrico, prospectivo y observacional cuyo objetivo fue evaluar los pacientes dados de alta. Se realizaron pruebas de función pulmonar, detección de biomarcadores en plasma circulante y radiografía y TC de tórax durante las visitas ambulatorias. Resultados En total 313 pacientes, de 61,12±12,26 años, de los 481 incluidos estuvieron disponibles. La proporción de pacientes con DLCO<80% fue del 54,6 y del 47% a los 60 y 180 días. Los factores que se sociaron a la alteración de la difusión a los 6 meses fueron el sexo femenino (OR: 2,97; IC del 95%: 1,74-5,06; p=0,001), la edad (OR: 1,03; IC del 95%: 1,01-1,05; p=0,005) y la puntuación RALE más alta (OR: 1,22; IC del 95%: 1,06-1,40; p=0,005). Los pacientes con alteración de la difusión pulmonar mostraron niveles más altos de MMP-7 (11,54±8,96 frente a 6,71±4,25; p=0,001) y periostina (1,11±0.07 frente a 0,84±0,40; p=0,001). Se le realizó una TC a 226 pacientes de los cuales 149 (66%) presentaban secuelas radiológicas de la COVID-19. En los pacientes graves, el 68,35% mostraban opacidades en vidrio esmerilado y el 38,46%, bandas parenquimatosas. Los cambios fibróticos tempranos se asociaron a niveles más altos de MMP7 (13,20±9,20 frente a 7,92±6,32; p=0,001), MMP1 (10,40±8,21 frente a 6,97±8,89; p=0,023), y periostina (1,36±0,93 frente a 0,87±0,39; p=0,001). Conclusión Casi la mitad de los pacientes con neumonía moderada o grave por COVID-19 presentaba alteración de la difusión pulmonar 6 meses después del alta. Los pacientes graves mostraban lesiones fibróticas en laTC y un aumento de los biomarcadores séricos relacionados con la fibrosis pulmonar

Circulating levels of calprotectin, a signature of neutrophil activation in prediction of severe respiratory failure in COVID-19 patients: a multicenter, prospective study (CalCov study).

OBJECTIVE: Severe COVID-19 is characterized by a dysregulated immune response in which neutrophils play a critical role. Calprotectin reflects neutrophil activation and is involved in the self-amplifying thrombo-inflammatory storm in severe COVID-19. We aimed to evaluate the role of calprotectin in early prediction of severity in COVID-19 patients. METHODS: This was a multicenter prospective observational study enrolling consecutive adult COVID-19 patients. On arrival to emergency department, blood samples were collected for laboratory tests, including serum calprotectin. The primary outcome was severe respiratory failure requiring invasive mechanical ventilation and the secondary outcome was need for Intensive Care Unit (ICU) admission. RESULTS: Study population included 395 patients, 57 (14.4%) required invasive mechanical ventilation and 100 (25.3%) were admitted to ICU. Median serum calprotectin levels were significantly higher in intubated (3.73 mg/L vs. 2.63 mg/L; p < 0.001) and ICU patients (3.48 mg/L vs. 2.60 mg/L; p = 0.001). Calprotectin showed a significant accuracy to predict the need for invasive mechanical ventilation (ROC AUC 0.723) and ICU admission (ROC AUC 0.650). In multivariate analysis, serum calprotectin was an independent predictor of invasive mechanical ventilation (OR 1.161) and ICU admission (OR 1.068). CONCLUSION: Serum calprotectin can be used as an early predictor of severity in COVID-19 patients.

Lung Function, Radiological Findings and Biomarkers of Fibrogenesis in a Cohort of COVID-19 Patients Six Months After Hospital Discharge.

INTRODUCTION: Impairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia. METHODS: COVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits. RESULTS: In total, 313, aged 61.12 ± 12.26 years, out of 481 included patients were available. The proportion of patients with DLCO < 80% was 54.6% and 47% at 60 and 180 days. Associated factors with diffusion impairment at 6 months were female sex (OR: 2.97, 95%CI 1.74-5.06, p = 0.001), age (OR: 1.03, 95% CI: 1.01-1.05, p = 0.005), and peak RALE score (OR: 1.22, 95% CI 1.06-1.40, p = 0.005). Patients with altered lung diffusion showed higher levels of MMP-7 (11.54 ± 8.96 vs 6.71 ± 4.25, p = 0.001), and periostin (1.11 ± 0.07 vs 0.84 ± 0.40, p = 0.001). 226 patients underwent CT scan, of whom 149 (66%) had radiological sequelae of COVID-19. In severe patients, 68.35% had ground glass opacities and 38.46% had parenchymal bands. Early fibrotic changes were associated with higher levels of MMP7 (13.20 ± 9.20 vs 7.92 ± 6.32, p = 0.001), MMP1 (10.40 ± 8.21 vs 6.97 ± 8.89, p = 0.023), and periostin (1.36 ± 0.93 vs 0.87 ± 0.39, p = 0.001). CONCLUSION: Almost half of patients with moderate or severe COVID-19 pneumonia had impaired pulmonary diffusion six months after discharge. Severe patients showed fibrotic lesions in CT scan and elevated serum biomarkers involved in pulmonary fibrosis.

INTRODUCCIÓN: El deterioro de la función pulmonar en las pruebas correspondientes y las alteraciones radiológicas son las preocupaciones principales en los supervivientes de la COVID-19. Nuestro objetivo fue evaluar los parámetros de la función respiratoria, los cambios en la TC de tórax y la correlación con los biomarcadores en sangre periférica involucrados en la fibrosis pulmonar a los 2 y a los 6 meses tras la neumonía por SARS-CoV-2. MÉTODOS: El ensayo COVID-FIBROTIC (clinicaltrials.gov NCT04409275) es un estudio de cohortes multicéntrico, prospectivo y observacional cuyo objetivo fue evaluar los pacientes dados de alta. Se realizaron pruebas de función pulmonar, detección de biomarcadores en plasma circulante y radiografía y TC de tórax durante las visitas ambulatorias. RESULTADOS: En total 313 pacientes, de 61,12 ± 12,26 años, de los 481 incluidos estuvieron disponibles.La proporción de pacientes con DLCO < 80% fue del 54,6 y del 47% a los 60 y 180 días.Los factores que se asociaron a la alteración de la difusión a los 6 meses fueron el sexo femenino (OR: 2,97; IC del 95%: 1,74-5,06; p = 0,001), la edad (OR: 1,03; IC del 95%: 1,01-1,05; p = 0,005) y la puntuación RALE más alta (OR: 1,22; IC del 95%: 1,06-1,40; p = 0,005). Los pacientes con alteración de la difusión pulmonar mostraron niveles más altos de MMP-7 (11,54 ± 8,96 frente a 6,71 ± 4,25; p = 0,001) y periostina (1,11 ± 0.07 frente a 0,84 ± 0,40; p = 0,001). Se le realizó una TC a 226 pacientes de los cuales 149 (66%) presentaban secuelas radiológicas de la COVID-19. En los pacientes graves, el 68,35% mostraban opacidades en vidrio esmerilado y el 38,46%, bandas parenquimatosas. Los cambios fibróticos tempranos se asociaron a niveles más altos de MMP7 (13,20 ± 9,20 frente a 7,92 ± 6,32; p = 0,001), MMP1 (10,40 ± 8,21 frente a 6,97 ± 8,89; p = 0,023), y periostina (1,36 ± 0,93 frente a 0,87 ± 0,39; p = 0,001). CONCLUSIÓN: Casi la mitad de los pacientes con neumonía moderada o grave por COVID-19 presentaba alteración de la difusión pulmonar 6 meses después del alta. Los pacientes graves mostraban lesiones fibróticas en laTC y un aumento de los biomarcadores séricos relacionados con la fibrosis pulmonar.

Treatment and prevention of ocular motility restrictions with amniotic membrane transplantation.

We intend to investigate the indications, complications, and final results of amniotic membrane (AM) transplantation in ocular motility restrictions. Surgeons have tried to prevent restrictive adhesions between the extraocular muscles and surrounding tissues because they cause unpredictable results. AM transplantation wrapping extraocular musculature has been proposed as a technique with good results for this purpose. A search was carried out in Medline, Embase, Cochrane Library and Clinicaltrial, Lilac and Ibecs databases, using the indexed terms" amnion", "strabismus," "strabismus-subheading-surgery" and "ocular motility disorders." The only exclusion criteria were studies conducted in non-humans or studies with insufficient data on eye motility. No study was discarded for analysis because of language, age or methodology. This review includes 165 patients (223 eyes), with a mean follow-up of 11.49 months. The mean age was 21 years old, 47% were males and 57% were children. 14 studies conducted in humans were eligible: 4 single case, 8 case series, 1 cohort study and 1 randomized clinical trial. In the vast majority of these papers, use of AM transplantation to treat (12 out of 14 papers) or either to prevent (2 out of 14 papers) motility restrictions or restrictive strabismus secondary to muscular adhesions. All the studies except one presents very favorable results improving postsurgical eye motility. The cryopreservation method was more widely used, presenting a good safety profile with few adverse effects in the short and medium term. Significant improvement was reported in most patients after the use of amniotic membrane transplantation to treat or prevent ocular motility limitations. Very few complications or adverse effects were documented.

Discordant SOX-1 antibodies results in paraneoplastic Lambert-Eaton syndrome diagnosis by the clinical laboratory.

BACKGROUND: Anti-Sry-like high mobility group box 1 (anti SOX-1) proteins are rare onconeural antibodies associated with paraneoplastic Lambert-Eaton myasthenic syndrome (LEMS). Few patients with anti-SOX-1 antibodies and negative anti-glial nuclear antibody reactivity have been described to date. CASE SUBJECT AND METHODS: Our case involves a 72-year-old female patient with progressive girdle weakness, sensation of heaviness in the lower limbs, predominantly distal and associated with circulatory problems together with instability when walking, with a high suspicion of an autoimmune myopathic disorder. Immunoblot test for autoimmune myopathies antibodies detection were all negative. Onconeuronal antibodies were determined in serum by indirect immunofluorescence being negative as well. Given the high suspicion, we also checked for the presence of other antineuronal antibodies whose patterns are not visible by IIF. RESULTS: Onconeuronal antibodies by immunoblot for the following antibodies: Hu, Ri, Yo, Zic4, Tr, PCA-2, MA-TA, CV2, GAD65, Zic4, Titin, SOX1, Recoverin and Amp, revealed an unexpected clear band in SOX-1, which are highly suggestive of paraneoplastic LEMS. DISCUSSION: We hypothesize that discordant onconeuronal antibodies results were due to the fact that positivity in IIF is associated with other SOX-B group proteins (normally related to cases of non-paraneoplastic neuropathy), while negativity in IIF and subsequent confirmed presence of specific SOX1 antibody by immunoblot could indicate an underlying tumor.

Tumor mutational burden assessment in non-small-cell lung cancer samples: results from the TMB2 harmonization project comparing three NGS panels.

BACKGROUND: Tumor mutational burden (TMB) is a recently proposed predictive biomarker for immunotherapy in solid tumors, including non-small cell lung cancer (NSCLC). Available assays for TMB determination differ in horizontal coverage, gene content and algorithms, leading to discrepancies in results, impacting patient selection. A harmonization study of TMB assessment with available assays in a cohort of patients with NSCLC is urgently needed. METHODS: We evaluated the TMB assessment obtained with two marketed next generation sequencing panels: TruSight Oncology 500 (TSO500) and Oncomine Tumor Mutation Load (OTML) versus a reference assay (Foundation One, FO) in 96 NSCLC samples. Additionally, we studied the level of agreement among the three methods with respect to PD-L1 expression in tumors, checked the level of different immune infiltrates versus TMB, and performed an inter-laboratory reproducibility study. Finally, adjusted cut-off values were determined. RESULTS: Both panels showed strong agreement with FO, with concordance correlation coefficients (CCC) of 0.933 (95% CI 0.908 to 0.959) for TSO500 and 0.881 (95% CI 0.840 to 0.922) for OTML. The corresponding CCCs were 0.951 (TSO500-FO) and 0.919 (OTML-FO) in tumors with <1% of cells expressing PD-L1 (PD-L1<1%; N=55), and 0.861 (TSO500-FO) and 0.722 (OTML-FO) in tumors with PD-L1≥1% (N=41). Inter-laboratory reproducibility analyses showed higher reproducibility with TSO500. No significant differences were found in terms of immune infiltration versus TMB. Adjusted cut-off values corresponding to 10 muts/Mb with FO needed to be lowered to 7.847 muts/Mb (TSO500) and 8.380 muts/Mb (OTML) to ensure a sensitivity >88%. With these cut-offs, the positive predictive value was 78.57% (95% CI 67.82 to 89.32) and the negative predictive value was 87.50% (95% CI 77.25 to 97.75) for TSO500, while for OTML they were 73.33% (95% CI 62.14 to 84.52) and 86.11% (95% CI 74.81 to 97.41), respectively. CONCLUSIONS: Both panels exhibited robust analytical performances for TMB assessment, with stronger concordances in patients with negative PD-L1 expression. TSO500 showed a higher inter-laboratory reproducibility. The cut-offs for each assay were lowered to optimal overlap with FO.

Decision support system through automatic algorithms and electronic request in diagnosis of anaemia for primary care patients.

INTRODUCTION: An appropriate management of anaemia laboratory tests is crucial for a correct diagnosis and treatment. A non-sequential "shotgun" approach (where every anaemia related test is ordered) causes workload and cost increases and could be potentially harmful. We have implemented a Decision Support System through our laboratory information system (LIMS) based on reflexive algorithms and automatic generation of interpretative reports specifically in diagnosis of anaemia for primary care patients. MATERIALS AND METHODS: When a request contained an "Anaemia Suspicion Study" profile, more than twenty automatic reflexive rules were activated in our LIMS based upon laboratory results. These rules normally involved the addition of reflexive tests. A final report was automatically generated for each interpretation which was always reviewed for their validity by two staff pathologists. We measured the impact of this system in the ordering of most common anaemia related tests and if a proper treatment was established based on the interpretive report. RESULTS: From all the studies performed, only 12% were positive being "iron deficiency" and "anaemia of chronic disease" the most frequent causes, 62% and 17%, respectively. Proper treatment was established in 88% of these anaemic patients. Total iron, transferrin, ferritin, folate and vitamin B12 demand decreased substantially after implementation representing a cost reduction of 40% only for these five tests. CONCLUSIONS: Our system has easily improved patient outcomes, advising on individual clinical cases. We have also noticeably reduced the number of over-requested tests and laboratory costs.

Safe use of systemic bevacizumab for respiratory recurrent papillomatosis in two children.

Recurrent respiratory papillomatosis can be a devastating condition for a child, with severe consequences. Currently, there is no proven successful medical treatment. We describe the use of systemic bevacizumab to treat two children affected by aggressive recurrent respiratory papillomatosis. Respiratory symptoms and quality of life improved dramatically in both patients, without observing any toxicity. The only complication was mild proteinuria. Systemic bevacizumab is a promising adjuvant treatment in aggressive recurrent respiratory papillomatosis in children. It is effective and well tolerated. Further studies are needed to establish the optimal dosing frequency and duration of therapy. Laryngoscope, 129:1001-1004, 2019.

Computer physician order entry (CPOE) as a strategy to estimate laboratory activity and costs associated with cancer clinical trials.

INTRODUCTION: Most of clinical laboratories are not properly reimbursed for their activity related to clinical trials (CTs) conducted in their institutions due to a lack of measurement strategies. We implemented a specific computer physician order entry (CPOE) environment for CTs in order to facilitate ordering to providers and estimate the associated costs to be compared with the standard of care (SOC). MATERIALS AND METHODS: Four specific electronic formularies, restricted to two new virtual CTs clinical services (onco - CT and haemo - CT), were implemented in January 2015. For each clinical trial displayed in the panels there were several box-cells that contained several profiles based on the different phase of the trials. Tests included in the profiles were the tests required by protocol. Laboratory costs (€) per patient were compared between the CTs services and their regular outpatients clinical services (onco - Out and haemo - Out, considered the SOC) for three years. RESULTS: Costs per patient were higher for CTs services and increased progressively each year (25%, 70% and 70% and 0.6%, 2.7% and 17% in 2015, 2016 and 2017 for Oncology and Haematology, respectively). Taking into account all these differences and the number of patients attending a total difference in expense of + 130,377.7 € for the period 2015-2017 was obtained between CTs and outpatients services. CONCLUSIONS: Strategies through CPOE systems based on restricted and specific profiles for CTs ordering are a promising tool that can improve laboratory associated costs estimation and provide robust evidence in reimbursement negotiation processes with CTs sponsors.

"Send & hold" clinical decision support rules improvement to reduce unnecessary testing of vitamins A, E, K, B1, B2, B3, B6 and C.

BACKGROUND: We assessed the impact of several "send & hold" clinical decision support rules (CDSRs) within the electronical request system for vitamins A, E, K, B1, B2, B3, B6 and C for all outpatients at a large health department. METHODS: When ordered through electronical request, providers (except for all our primary care physicians who worked as a non-intervention control group) were always asked to answer several compulsory questions regarding main indication, symptomatology, suspected diagnosis, vitamin active treatments, etc., for each vitamin test using a drop-down list format. After samples arrival, tests were later put on hold internally by our laboratory information system (LIS) until review for their appropriateness was made by two staff pathologists according to the provided answers and LIS records (i.e. "send & hold"). The number of tests for each analyte was compared between the 10-month period before and after CDSRs implementation in both groups. RESULTS: After implementation, vitamins test volumes decreased by 40% for vitamin A, 29% for vitamin E, 42% for vitamin K, 37% for vitamin B1, 85% for vitamin B2, 68% for vitamin B3, 65% for vitamin B6 and 59% for vitamin C (all p values 0.03 or lower except for vitamin B3), whereas in control group, the majority increased or remained stable. In patients with rejected vitamins, no new requests and/or adverse clinical outcome comments due to this fact were identified. CONCLUSIONS: "Send & hold" CDSRs are a promising informatics tool that can support in utilization management and enhance the pathologist's leadership role as tests specialist.

PAI-1 levels are related to insulin resistance and carotid atherosclerosis in subjects with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCH) is a primary atherogenic dyslipidemia with insulin resistance and increased cardiovascular risk. Plasminogen activator inhibitor type 1 (PAI-1) and myeloperoxidase (MPO) activity are associated with proinflammatory and atherothrombotic risk. Our aim was to study the role played by PAI-1 and MPO activity in the carotid atherosclerosis prevalence in FCH subjects. 36 FCH unrelated subjects (17 women) were matched by age and body weight with 36 healthy normolipidemic subjects (19 female). Blood lipids, glucose, insulin, insulin resistance (homeostasis model assessment (HOMA)), MPO, and PAI-1 were determined in both groups. Carotid intima media thickness (IMT) was measured by the same investigator by standardized protocol. No differences in age, body mass index (BMI) or waist circumference were observed between the two groups. HOMA and PAI-1 values were higher in the FCH group, reaching statistical significance in those subjects with insulin resistance. In addition, PAI-1 values correlated significantly with metabolic syndrome components and carotid IMT. It is known that the elevated cardiovascular risk that characterizes FCH is frequently associated with insulin resistance. We have detected that two known proinflammatory and proatherothrombotic factors (MPO and PAI-1) are significantly elevated in FCH subjects with insulin resistance. These results could partly explain the high cardiovascular risk present in FCH subjects.