Effectiveness and Safety of Postoperative Hospital at Home for Surgical Patients: A Cohort Study.

OBJECTIVE: To determine the feasibility and effectiveness of a Hospital at Home (HaH) enabled early transfer pathways for surgical patients. BACKGROUND: HaH serves as a safe alternative to traditional hospitalization by providing acute care to patients in their homes through a comprehensive range of hospital-level interventions. To our knowledge, no studies have been published to date reporting a large cohort of early home-transferred patients after surgery through a HaH unit. METHODS: Cohort study enrolling every patient admitted to the HaH unit of a tertiary hospital who underwent any of 6 surgeries with a predefined early transfer pathway and fitting both general and surgery inclusion criteria (clinical and hemodynamic stability, uncomplicated surgery, presence of a caregiver, among others) from November 2021 to May 2023. Protocols were developed for each pathway between surgical services and HaH to deliver the usual postoperative care in the home setting. Discharge was decided according to protocol. An urgent escalation pathway was also established. RESULTS: During the study period, 325 patients were included: 141 were bariatric surgeries, 85 kidney transplants, 45 thoracic surgeries, 37 cystectomies, 10 appendicectomies, and 7 ventral hernia repairs. The overall escalation of care during HaH occurred in 7.3% of patients and 30-day readmissions in 7%. Most adverse events were managed at home and the overall mortality was zero. The total mean length of stay was 8 days (interquartile range 2-14), and patients with HaH were transferred home 3 days (interquartile range 1-6) earlier than the usual pathway; a total of 1551 bed-days were saved. CONCLUSIONS: The implementation of early home transfer pathways for surgical patients through HaH is feasible and effective, with favorable safety outcomes.

Time intervals in the care pathway to cancer diagnosis during the COVID-19 pandemic: A large retrospective study from a high-volume center.

Despite extensive research on cancer care during the COVID-19 pandemic, evidence on the impact on prediagnostic time intervals is lacking. To better understand how COVID-19 changed the pathway to diagnosis of cancer, we examined the length of intervals from symptom onset to diagnosis for 13 common cancer types with known clinical stage over 1-year nonpandemic period (March 2019 to March 2020; N = 844) and three biannual COVID periods (March 2020 to September 2021; N = 1172). We analyzed the patient interval (from first symptoms to presentation to a physician), the primary care/emergency department interval (from presentation with relevant symptoms to a primary care or emergency department physician to referral to a hospital-based diagnosis center) and the hospital interval (from referral to diagnosis). Compared to nonpandemic data, there were significant changes across COVID periods. The pandemic mostly impacted patient intervals for cancers diagnosed over the first 6 months after onset in March 2020. Overall median patient intervals were longest in the early COVID period (39 [IQR 22-64] days) and shortest in the nonpandemic period (20 [IQR 13-30] days; Kruskal-Wallis test [χ2 ], P < .0001). Differences in clinical stage between periods were relevant, with cancers from the mid-period (September 2020 to March 2021) showing the most advanced stage. A shift to later stage was plausibly a result of delayed intervals in the early COVID period. Since intervals are eventually relevant to prognosis, our results provide a baseline against which the impact of improvement strategies to minimize the negative outcomes of COVID-19-associated cancer delays can be assessed and implemented.

Effects of everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study.

BACKGROUND AND AIM: reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain. METHODS: the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels ≤ 5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated. RESULTS: in the EVR + rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF + TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2), with significant (p < 0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups. CONCLUSION: EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation.

Application of systems biology-based in silico tools to optimize treatment strategy identification in Still's disease.

BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are manifestations of an autoinflammatory disorder with complex pathophysiology and significant morbidity, together also termed Still's disease. The objective of the current study is to set in silico models based on systems biology and investigate the optimal treat-to-target strategy for Still's disease as a proof-of-concept of the modeling approach. METHODS: Molecular characteristics of Still's disease and data on biological inhibitors of interleukin (IL)-1 (anakinra, canakinumab), IL-6 (tocilizumab, sarilumab), and glucocorticoids as well as conventional disease-modifying anti-rheumatic drugs (DMARDs, methotrexate) were used to construct in silico mechanisms of action (MoA) models by means of Therapeutic Performance Mapping System (TPMS) technology. TPMS combines artificial neuronal networks, sampling-based methods, and artificial intelligence. Model outcomes were validated with published expression data from sJIA patients. RESULTS: Biologicals demonstrated more pathophysiology-directed efficiency than non-biological drugs. IL-1 blockade mainly acts on proteins implicated in the innate immune system, while IL-6 signaling blockade has a weaker effect on innate immunity and rather affects adaptive immune mechanisms. The MoA models showed that in the autoinflammatory/systemic phases of Still's disease, in which the innate immunity plays a pivotal role, the IL-1ß-neutralizing antibody canakinumab is more efficient than the IL-6 receptor-inhibiting antibody tocilizumab. MoA models reproduced 67% of the information obtained from expression data. CONCLUSIONS: Systems biology-based modeling supported the preferred use of biologics as an immunomodulatory treatment strategy for Still's disease. Our results reinforce the role for IL-1 blockade on innate immunity regulation, which is critical in systemic autoinflammatory diseases. This further encourages early use on Still's disease IL-1 blockade to prevent the development of disease or drug-related complications. Further analysis at the clinical level will validate the findings and help determining the timeframe of the window of opportunity for canakinumab treatment.

Características clínicas de las pericarditis y miopericarditis diagnosticadas en urgencias y factores asociados con la necesidad de hospitalización / Clinical features of pericarditis with and without myocardial involvement diagnosed in the emergency department and factors associated with need for hospitalization

Objetivo: Analizar los episodios de pericarditis aguda (PA) diagnosticados en urgencias en función de la edad y de la afectación miocárdica (miopericarditis, MioP), y determinar los factores asociados a hospitalización. Método: Estudio observacional, descriptivo, unicéntrico de casos consecutivos, con análisis retrospectivo de todos los casos diagnosticados de PA en urgencias durante 10 años (2008-2017), y revisión de las características clínicas, ECG, analíticas y ecográficas (en MioP). Se compararon características clínicas según la edad (< 50 y $ 50 años) y existencia de MioP. Los factores asociados a hospitalización (PA y MioP) se identificaron de forma cruda y ajustada por las diferencias clínicas entre grupos. Resultados: Se diagnosticaron 983 PA (34% mujeres, mediana de edad: 42 años). Los pacientes más jóvenes referían con mayor frecuencia dolor torácico (DT) punzante y modificable con la respiración o cambios posturales, y los más mayores tenían más comorbilidades cardiovasculares, refirieron más frecuentemente DT opresivo y generaron mayor sospecha de síndrome coronario agudo. Las alteraciones en el ECG (OR = 4,26; IC95% = 1,89-9,59) se asociaron a MioP (72 casos, 7%). Ingresaron 62 PA (6%), hecho asociado a antecedente de insuficiencia renal (OR = 4,83; IC95% = 1,66-14,05), DT que se modifica con movimientos respiratorios/posturales (OR = 0,54, IC95% = 0,29-0,99), taquicardia (OR = 2,29, IC95% = 1,15-4,55) y MioP (OR = 8,73, IC95% = 4,65-16,38). Ingresaron 24 MioP (33%), hecho asociado a alteraciones en la ecoscopia dirigida (protocolo FOCUS; OR = 13,72, IC95% = 1,80-104). Conclusiones: La edad puede condicionar la presentación clínica en los pacientes con PA. Las alteraciones en el segmento ST en el ECG son sugestivos de implicación miocárdica. La insuficiencia renal, la taquicardia y la MioP son factores que incrementan la decisión de hospitalización en las PA; mientras que en las MioP, las alteraciones ecográficas

Objectives: To analyze the clinical features of acute pericarditis diagnosed in the emergency department according to patient age and myocardial involvement (myopericarditis) and to determine factors associated with hospitalization. Methods: Retrospective, descriptive, observational, single-center study of consecutive patients. We analyzed all cases of pericarditis diagnosed in the emergency department over a period of 10 years (2008-2017), reviewing clinical, electrocardiographic, and laboratory findings as well as ultrasound imaging for myocardial involvement. Characteristics were analyzed by age (under 50 years or 50 or older) and presence or not of myocardial involvement. Factors associated with hospitalization for both pericarditis and myopericarditis were identified by crude and adjusted odds ratios (ORs). Results: A total of 983 patients were diagnosed with pericarditis (34% women, mean age, 42 years). The younger patients more often reported sharp chest pain modified by breathing or posture changes. Older patients had more concurrent cardiovascular disease and described chest pain as pressure (oppressive); acute coronary syndrome was suspected more often in the older patients. The only independent predictor of myopericarditis was a finding of electrocardiographic abnormalities, recorded in 72 cases (7%) (OR, 4.26; 95% CI, 1.89-9.59). Sixty-two patients (6%) were admitted for pericarditis. Associated factors were renal insufficiency (OR, 4.83; 95% CI, 1.66-14.05), pain modified by breathing or posture changes (OR, 0.54; 95% CI, 0.29-0.99), tachycardia (OR, 2.29; 95% CI, 1.15-4.55), and myopericarditis (OR, 8.73; 95% CI, 4.65-16.38). Admission of 24 patients (33%) for myocarditis was related to focused cardiac ultrasound findings (OR, 13.72; 95% CI, 1.80-104). Conclusions: Age may affect the presentation of pericarditis. ST segment abnormalities on an electrocardiogram suggest myocardial involvement. Renal insufficiency, tachycardia, and myocardial involvement are the factors associated with a decision to admit patients with pericarditis. Ultrasound findings are associated with admission for myopericarditis

Clinical features of pericarditis with and without myocardial involvement diagnosed in the emergency department and factors associated with need for hospitalization. / Características clínicas de las pericarditis y miopericarditis diagnosticadas en urgencias y factores asociados con la necesidad de hospitalización.

OBJECTIVES: To analyze the clinical features of acute pericarditis diagnosed in the emergency department according to patient age and myocardial involvement (myopericarditis) and to determine factors associated with hospitalization. MATERIAL AND METHODS: Retrospective, descriptive, observational, single-center study of consecutive patients. We analyzed all cases of pericarditis diagnosed in the emergency department over a period of 10 years (2008-2017), reviewing clinical, electrocardiographic, and laboratory findings as well as ultrasound imaging for myocardial involvement. Characteristics were analyzed by age (under 50 years or 50 or older) and presence or not of myocardial involvement. Factors associated with hospitalization for both pericarditis and myopericarditis were identified by crude and adjusted odds ratios (ORs). RESULTS: A total of 983 patients were diagnosed with pericarditis (34% women, mean age, 42 years). The younger patients more often reported sharp chest pain modified by breathing or posture changes. Older patients had more concurrent cardiovascular disease and described chest pain as pressure (oppressive); acute coronary syndrome was suspected more often in the older patients. The only independent predictor of myopericarditis was a finding of electrocardiographic abnormalities, recorded in 72 cases (7%) (OR, 4.26; 95% CI, 1.89-9.59). Sixty-two patients (6%) were admitted for pericarditis. Associated factors were renal insufficiency (OR, 4.83; 95% CI, 1.66-14.05), pain modified by breathing or posture changes (OR, 0.54; 95% CI, 0.29-0.99), tachycardia (OR, 2.29; 95% CI, 1.15- 4.55), and myopericarditis (OR, 8.73; 95% CI, 4.65-16.38). Admission of 24 patients (33%) for myocarditis was related to focused cardiac ultrasound findings (OR, 13.72; 95% CI, 1.80-104). CONCLUSION: Age may affect the presentation of pericarditis. ST segment abnormalities on an electrocardiogram suggest myocardial involvement. Renal insufficiency, tachycardia, and myocardial involvement are the factors associated with a decision to admit patients with pericarditis. Ultrasound findings are associated with admission for myopericarditis.

OBJETIVO: Analizar los episodios de pericarditis aguda (PA) diagnosticados en urgencias en función de la edad y de la afectación miocárdica (miopericarditis, MioP), y determinar los factores asociados a hospitalización. METODO: Estudio observacional, descriptivo, unicéntrico de casos consecutivos, con análisis retrospectivo de todos los casos diagnosticados de PA en urgencias durante 10 años (2008-2017), y revisión de las características clínicas, ECG, analíticas y ecográficas (en MioP). Se compararon características clínicas según la edad (< 50 y $ 50 años) y existencia de MioP. Los factores asociados a hospitalización (PA y MioP) se identificaron de forma cruda y ajustada por las diferencias clínicas entre grupos. RESULTADOS: Se diagnosticaron 983 PA (34% mujeres, mediana de edad: 42 años). Los pacientes más jóvenes referían con mayor frecuencia dolor torácico (DT) punzante y modificable con la respiración o cambios posturales, y los más mayores tenían más comorbilidades cardiovasculares, refirieron más frecuentemente DT opresivo y generaron mayor sospecha de síndrome coronario agudo. Las alteraciones en el ECG (OR = 4,26; IC95% = 1,89-9,59) se asociaron a MioP (72 casos, 7%). Ingresaron 62 PA (6%), hecho asociado a antecedente de insuficiencia renal (OR = 4,83; IC95% = 1,66-14,05), DT que se modifica con movimientos respiratorios/posturales (OR = 0,54, IC95% = 0,29-0,99), taquicardia (OR = 2,29, IC95% = 1,15-4,55) y MioP (OR = 8,73, IC95% = 4,65-16,38). Ingresaron 24 MioP (33%), hecho asociado a alteraciones en la ecoscopia dirigida (protocolo FOCUS; OR = 13,72, IC95% = 1,80-104). CONCLUSIONES: La edad puede condicionar la presentación clínica en los pacientes con PA. Las alteraciones en el segmento ST en el ECG son sugestivos de implicación miocárdica. La insuficiencia renal, la taquicardia y la MioP son factores que incrementan la decisión de hospitalización en las PA; mientras que en las MioP, las alteraciones ecográficas.

Etanercept plus colchicine treatment in a child with tumour necrosis factor receptor-associated periodic syndrome abolishes auto-inflammatory episodes without normalising the subclinical acute phase response.

UNLABELLED: We investigated the cause of hereditary periodic fever syndrome in a Spanish child with recurrent long episodes of fever, migratory skin rash, myalgia, arthralgia, conjunctivitis and abdominal pain. Infectious and autoimmune causes were ruled out. No familial history was reported. Analysis of the tumour necrosis factor receptor superfamily 1A (TNFRSF1A) gene identified a missense mutation (G36E) on exon 3. The absence of this variant in the patient's parents and in controls identified it as a de novo disease-associated mutation. Clinical symptoms disappeared with administration of etanercept; however, levels of acute-phase reactants remained increased and could not be stabilised by the addition of colchicine. We believe that this patient gained some symptomatic relief with etanercept therapy, although not enough to completely avoid the risk of amyloidosis. Thus it is debatable whether etanercept alone or combined with other drugs, is the treatment of choice for patients with tumour necrosis factor receptor-associated periodic syndrome. CONCLUSION: Since there is variability in treatment responses among different patients with tumour necrosis factor receptor-associated periodic syndrome, we suggest that a systematic evaluation of acute-phase reactants, especially SAA-1, could be useful in maintaining or modifying a given therapeutic approach in these patients.

Clinical and genetic heterogeneity among Spanish patients with recurrent autoinflammatory syndromes associated with the CIAS1/PYPAF1/NALP3 gene.

OBJECTIVE: To investigate the involvement of the CIAS1/PYPAF1/NALP3 gene in 7 unrelated Spanish families with recurrent autoinflammatory diseases characterized by early onset, recurrent fever, and a chronic urticarial rash, in whom a clinical diagnosis of cryopyrin-associated periodic syndromes (CAPS) is suspected. METHODS: Clinical symptoms, results of laboratory analyses, and data on previous treatments in members of the 7 families were recorded on a questionnaire specific for hereditary autoinflammatory diseases. All coding regions and intronic flanking boundaries of the CIAS1/PYPAF1/NALP3 gene were amplified by polymerase chain reaction and sequenced. RESULTS: Five different missense mutations, including 2 de novo and 1 previously unreported mutation (R488K), were identified in exon 3 of the CIAS1/PYPAF1/NALP3 gene in 5 of the 7 affected families. Expanded genetic analysis among the healthy individuals identified incomplete penetrance in 2 families. No mutations were found in 2 of the 3 patients with chronic infantile neurologic, cutaneous, articular (CINCA) syndrome/neonatal-onset multisystem inflammatory disease (NOMID). CONCLUSION: The clinical data suggested a diagnosis of familial cold-induced autoinflammatory syndrome in 3 families, CINCA/NOMID syndrome in 3 others, and a possible Muckle-Wells syndrome, whereas mutational analysis showed different CIAS1/PYPAF1/NALP3 missense mutations in 5 families. These data are consistent with a common molecular basis of these diseases and highlights the phenotypic heterogeneity among CIAS1/PYPAF1/NALP3 gene-associated syndromes. The previously unreported mutation and the incomplete penetrance found in 2 families expand the genetic basis underlying these autoinflammatory syndromes. These findings should alert clinicians to the possible genetic basis of these conditions, even in the absence of a family history, in their attempts to establish an accurate diagnosis and the optimal therapeutic approach.

The west side story: MEFV haplotype in Spanish FMF patients and controls, and evidence of high LD and a recombination "hot-spot" at the MEFV locus.

Mutations at the MEFV gene cause, with various degrees of penetrance, familial Mediterranean fever (FMF). This disease is more prevalent in the Middle East than elsewhere, and most studies have focused on those populations. However, FMF occurs also in the Western Mediterranean and these populations should be taken into account for a complete view of FMF. We have analyzed intragenic MEFV SNPs in Spanish and Chueta (descendants of converted Jews) FMF patients and controls, and this constitutes the first systematic survey of normal MEFV SNP haplotype structure and variability. Our findings have allowed us to systematize the nomenclature of MEFV haplotypes and show that there is strong linkage disequilibrium (LD) at the MEFV locus and an intragenic recombination hot spot. The high local LD, regardless the recombination hot spot, is responsible for the limited diversity of the MEFV control haplotypes found in the Spanish population and it suggests that it may be a common feature to all Mediterranean populations. The MEFV mutation spectrum in Spain is quite diverse, and similar to those of France and Italy. On the contrary, the Chueta spectrum was poorer and closer to that of North African Jews, suggesting a direct connection with the Jewish diaspora.

A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease and around 30 mutations have been reported to date. Colchicine is the standard FMF treatment today, and prevents both attacks and amyloid deposition in 95% of patients. Here we describe a three-generation Spanish kindred with five family members affected by a severe periodic inflammatory disorder associated with renal AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite FMF disease was made based on the Tel-Hashomer criteria set. Genetic analyses revealed that all subjects were heterozygous for the new H478Y MEFV variant, segregating with the disease. In addition, mutations in the TNFRSF1A and CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory periodic syndromes, were ruled out. However, the dominant inheritance of the disease, the long fever episodes with a predominant joint involvement, and the resistance to colchicine in these patients raise the question of whether the periodic syndrome seen in this kindred is a true FMF disease with unusual manifestations or rather another MEFV-associated periodic syndrome. We conclude that the new H478Y MEFV mutation is the dominant pathological variant causing the inflammatory periodic syndrome in this kindred and that full-length analyses of the MEFV gene are needed to obtain an adequate diagnosis of patients with clinical suspicion of a hereditary periodic fever syndrome, especially those from non-ancestral populations.

Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes.

OBJECTIVE: To investigate the prevalence of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among outpatients presenting with recurrent fevers and clinical features consistent with TRAPS. METHODS: Mutational screening was performed in affected members of 18 families in which multiple members had symptoms compatible with TRAPS and in 176 consecutive subjects with sporadic (nonfamilial) "TRAPS-like" symptoms. Plasma concentrations of soluble tumor necrosis factor receptor superfamily 1A (sTNFRSF1A) were measured, and fluorescence-activated cell sorter analysis was used to measure TNFRSF1A shedding from monocytes. RESULTS: Eight novel and 3 previously reported TNFRSF1A missense mutations were identified, including an amino acid deletion (Delta D42) in a Northern Irish family and a C70S mutation in a Japanese family, both reported for the first time. Only 3 TNFRSF1A variants were found in patients with sporadic TRAPS (4 of 176 patients). Evidence for nonallelic heterogeneity in TRAPS-like conditions was found: 3 members of the "prototype familial Hibernian fever" family did not possess C33Y, present in 9 other affected members. Plasma sTNFRSF1A levels were low in TRAPS patients in whom renal amyloidosis had not developed, but also in mutation-negative symptomatic subjects in 4 families, and in 14 patients (8%) with sporadic TRAPS. Reduced shedding of TNFRSF1A from monocytes was demonstrated in vitro in patients with the T50M and T50K variants, but not in those with other variants. CONCLUSION: The presence of TNFRSF1A shedding defects and low sTNFRSF1A levels in 3 families without a TNFRSF1A mutation indicates that the genetic basis among patients with "TRAPS-like" features is heterogeneous. TNFRSF1A mutations are not commonly associated with nonfamilial recurrent fevers of unknown etiology.