Postoperative day one systemic inflammatory response syndrome is a powerful early biomarker of clinically relevant pancreatic fistula.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most feared complication following pancreaticoduodenectomy (PD). There is increasing evidence that very early postoperative factors can be helpful to identify high-risk patients. The aim of this study is to analyze whether postoperative day one (POD1) systemic inflammatory response can be used as an early biomarker of CR-POPF development. METHODS: All patients undergoing PD from 2014 to 2020 were considered. Variables were extracted from a prospectively held database. Clinical and perioperative variables, including POD1 systemic inflammatory response syndrome (SIRS) and C-reactive protein level were collected. To elucidate the independent role of early CR-POPF biomarkers, multivariate hierarchical logistic regression analyses were planned. RESULTS: Out of 243, 213 patients were included in this analysis. CR-POPF occurred in 49 (23.0%) patients and 90-day mortality was 1.4%. POD1 SIRS was reported in 65 (30.5%) patients. Following hierarchical logistic regression analyses, CR-POPF was independently associated with body mass index (OR = 2.787, p = 0.003), soft pancreatic texture (OR = 4.258, p = 0.002) and POD1 SIRS (OR = 50.067, p = 0.001). CONCLUSION: POD1 SIRS is powerfully associated with CR-POPF and therefore it could be used as a tool to optimize postoperative care of PD patients. Further prospective studies are needed to validate these findings.

Assessing surgical difficulty in locally advanced mid-low rectal cancer: the accuracy of two MRI-based predictive scores.

AIM: Predicting surgical difficulty is a critical factor in the management of locally advanced rectal cancer (LARC). This study evaluates the accuracy and external validity of a recently published morphometric score to predict surgical difficulty and additionally proposes a new score to identify preoperatively LARC patients with a high risk of having a difficult surgery. METHODS: This is a retrospective study based on the European MRI and Rectal Cancer Surgery (EuMaRCS) database, including patients with mid/low LARC who were treated with neoadjuvant chemoradiation therapy and laparoscopic total mesorectal excision (L-TME) with primary anastomosis. For all patients, pretreatment and restaging MRI were available. Surgical difficulty was graded as high and low based upon a composite outcome, including operative (e.g. duration of surgery) and postoperative variables (e.g. hospital stay). Score accuracy was assessed by estimating sensitivity, specificity and area under the receiver operating characteristic curve (AROC). RESULTS: In a total of 136 LARC patients, 17 (12.5%) were graded as high surgical difficulty. The previously published score (calculated on body mass index, intertuberous distance, mesorectal fat area, type of anastomosis) showed low predictive value (sensitivity 11.8%; specificity 92.4%; AROC 0.612). The new EuMaRCS score was developed using the following significant predictors of surgical difficulty: body mass index > 30, interspinous distance < 96.4 mm, ymrT stage ≥ T3b and male sex. It demonstrated high accuracy (AROC 0.802). CONCLUSION: The EuMaRCS score was found to be more sensitive and specific than the previous score in predicting surgical difficulty in LARC patients who are candidates for L-TME. However, this score has yet to be externally validated.

Cushing's syndrome in pregnancy. Laparoscopic adrenalectomy during pregnancy: the mainstay treatment.

INTRODUCTION: Cushing's syndrome (CS) is a rare disease in pregnancy and its differential diagnosis is complicated. It is usually confused with complicated pregnancy cases, such us preeclampsia and gestational diabetes. This usually leads to a delayed diagnosis and is also associated with severe materno-foetal complications. PURPOSE: We present a case of a pregnant woman in her third trimester of pregnancy with CS secondary to an adrenal adenoma without response to medical treatment who underwent laparoscopic adrenalectomy without complications. DISCUSSION: Most authors consider adrenalectomy as the first-choice treatment, since it presents higher rate of successful pregnancies. However, previously published cases did not reflect this stance. These publications prefer to maintain medical treatment, allowing pregnancy to go to term and delaying adrenalectomy after childbirth. We consider that experience in laparoscopic surgery, obstetric knowledge and resources now available, all offer sufficient guarantees to carry out the laparoscopic procedure to treat CS in pregnancy even in the third trimester. Laparoscopic adrenalectomy for CS in pregnancy is a safe and efficacious procedure allowing stopping the disease and curbing the dreadful consequences it may have for both mother and foetus.

The JAK2 46/1 haplotype does not predispose to CALR-mutated myeloproliferative neoplasms.

Somatic mutations in the CALR gene were recently discovered in a substantial proportion of Philadelphia-negative chronic myeloproliferative neoplasm (cMPN) patients lacking JAK2 and MPL mutations. Somatically acquired defects are not the only pathogenic mechanism involved in these disorders. Since germline JAK2 46/1 haplotype predisposes to cMPN-associated mutations, including JAK2V617F and MPLW515K7L, we evaluated whether the 46/1 haplotype also confers susceptibility to CALR-mutated cMPN, both in sporadic and familial cases. The single-nucleotide polymorphism rs10974944, which tags 46/1, was investigated in 155 sporadic MPN patients and 270 unrelated controls, as well as in 11 familial cMPN cases and 36 unaffected relative controls. As described elsewhere, the 46/1 haplotype was overrepresented, both in sporadic and familial cMPN. In sporadic cMPN, the JAK2 46/1 haplotype was closely associated with JAK2V617F (p = 0.0003) but not with JAK2-nonmutated cases. Analysis of CALR-mutated sporadic cMPN (n = 22) showed no association between CALR mutations and 46/1 haplotype (p = 0.87). Regarding the familial cMPN, the prevalence of carriers of the G allele was higher in familial (81.8%) than in sporadic (62%) cMPN, but it did not differ significantly (p = 0.3). Although we described a family with carriers of both JAK2V617F and CALR mutations, due to the low number of CALR-mutated familial cases, we could not determinate whether the JAK2 46/1 haplotype predisposes or does not to CALR-mutated familial cMPN. We conclude, for the first time, that the 46/1 haplotype, unlike JAK2V617F and MPLW515K7L, is not associated with CALR-mutated cMPN.

Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection.

The endoplasmic reticulum (ER) is where the major histocompatibility complex (MHC) class I molecules are loaded with epitopes to cause an immune cellular response. Most of the protein antigens are degraded in the cytoplasm to amino acids and few epitopes reach the ER. Antigen targeting of this organelle by Calreticulin (CRT) fusion avoids this degradation and enhances the immune response. We constructed a recombinant adenovirus to express the E7 antigen with an ER-targeting signal peptide (SP) plus an ER retention signal (KDEL sequence). In cell-culture experiments we demonstrated that this new E7 antigen, SP-E7-KDEL, targeted the ER. Infection of mice with this recombinant adenovirus that expresses SP-E7-KDEL showed interferon induction and tumour-protection response, similar to that provided by an adenovirus expressing the E7 antigen fused to CRT. This work demonstrated that just by adding a SP and the KDEL sequence, antigens can be targeted and retained in the ER with a consequent enhancement of immune response and tumour protection. These results will have significant clinical applications.

Parry-Romberg Syndrome and Temporal Lobe Refractory Epilepsy: Case Report.

The Parry-Romberg syndrome (PRS), also known as hemifacial atrophy, is a rare neurocutaneous disease with the prevalence of 1/700,000 cases. It is more common in women than men, with an early onset of disease usually within the first two decades of life. Even though the etiology of PRS is unknown, it is thought to be a multifactorial disease that involves hereditary, posttraumatic, autoimmune, infectious, and neoplastic factors. There are a variety of systemic manifestations described in PRS including neurological conditions that range from intractable headache to refractory epilepsy. The manifestations must be identified in a timely manner to ensure an early therapeutic intervention, considering that an appropriate approach during the initial phase might halt the disease progression and markedly improve the quality of life in these patients. This article is aimed to describe the case of a 23 years old female with left hemifacial atrophy and dermatologic, dental, and neurologic compromise, associated with refractory temporal lobe epilepsy evidenced in neuroimaging and electrodiagnostic testings.

MicroRNAs in Kidney Machine Perfusion Fluid as Novel Biomarkers for Graft Function. Normalization Methods for miRNAs Profile Analysis.

MicroRNAs (miRNAs) are post-transcriptional regulators that have emerged as promising biomarkers in kidney transplantation. Quantification of miRNAs can be analyzed by means of biological normalization. The purpose of normalization is to remove technical variation in data, which is not related to the biological changes under investigation. Proper normalization is critical for the correct analysis and interpretation of results. MATERIAL AND METHODS: A prospective cohort study was conducted on graft dysfunction in kidney transplantation from expanded criteria donors. After RNA extraction quantitative real-time polymerase chain reaction was performed. The exogenous spike-in normalization was used as technical normalization. Relative expression was calculated using the 2-ΔΔCt method and UniSp2 spike-in was used as reference for normalization. Results obtained were further analyzed by the application of the mean expression value that uses the calculated mean of all miRNAs in a given sample. RESULTS: The mean expression value approach confirmed the significance of a subset of the miRNAs previously identified for delayed graft function development and composed by miRNAs miR-486-5p, miR-144-3p, miR-142-5p, and miR-144-5p. CONCLUSIONS: MicroRNAs are becoming increasingly important as biomarkers in multiple disease processes including kidney transplantation. Perfusion fluid, particularly during hypothermic machine perfusion, provides a valuable pretransplantation source for identification of organ viability biomarkers. Although there is no clear consensus concerning the normalization technique, the mean expression value method shows the better normalization strategy.

Resultados preliminares del impacto de la COVID-19 en niños/as y adolescentes expuestos a maltrato intrafamiliar / Preliminary results of the impact of COVID-19 on children and adolescents exposed to intrafamily abuse

Resumen: Los datos preliminares confirman el impacto psicológico que la crisis por COVID-19 está provocando en niños y adolescentes de población comunitaria. Se desconoce cómo afecta a la población infantil que sufre maltrato intrafamiliar. El objetivo del estudio fue examinar el impacto emocional adicional que supone la medida de confinamiento en menores de edad expuestos a violencia de pareja hacia la mujer que recibían atención psicológica en la Región de Murcia. Ciento ochenta y cinco madres informaron vía telefónica cómo el confinamiento afectó a 269 niños/as de entre 0 y 18 años. También los 108 menores que tenían 6 años o más, cumplimentaron el listado sobre su propio estado emocional. El incremento en la incidencia de alteraciones psicológicas en esta población ha sido baja (1.1-4.8%), si bien entre aquellos que aumentó la sintomatología predominaron la desorganización comportamental y la alteración emocional. Asimismo, se comprobó que algunas variables (sexo, edad, días de confinamiento, conflicto familiar) contribuyeron al incremento de desorganización comportamental y estrés traumático/depresión. Es preciso desarrollar más trabajos en esta línea por las implicaciones que se pueden derivar tanto a nivel de diagnóstico como de tratamiento.

Abstract: Preliminary data confirm the psychological impact that the COVID-19 crisis is causing in children and adolescents in the community population. It is unknown how it affects the child population who suffer intrafamilial abuse. The objective of the study was to examine the additional emotional impact of the measure of confinement in minors exposed to intimate partner violence towards women who received psychological attention in the Region of Murcia. One hundred and eighty-five mothers reported, by telephone comunication, how the confinement affected to 269 children between the ages of 0 and 18. Also the 108 minors who were 6 years old or older completed the list on their own emotional state. The incidence increasement of psychological disorders within this population has been low (1.1-4.8%), although among those with increased symptoms, behavioral disorganization and emotional disturbance was predominant. Likewise, it was found that some variables (sex, age, days of confinement, family conflict) contributed to increase the behavioral disorganization and traumatic stress/depression. It is necessary to develop more research in this line due to the derived implications both at diagnosis and treatment levels.

[Intestinal transplantation in adults: present situation and future prospects]. / Trasplante intestinal del adulto. Situación actual y perspectivas de futuro.

Intestinal transplantation is becoming more firmly established as a treatment for intestinal failure in patients whose home parenteral nutrition regimens have caused serious side effects. Outcomes have improved spectacularly over recent years thanks to the refinement of surgical techniques and the introduction of new immunosuppressants, and also to greater experience in anesthetic and postoperative management of intestinal transplant patients. The main causes of high morbidity and mortality continue to be sepsis and acute rejection of the graft. Both graft and patient survival have improved with the advent of the immunosuppressant regimens based on Tacrolimus, although survival rates are still far below those reported for other solid organ transplants. The first intestinal transplant performed in Spain took place in July 2002 in our hospital and the results were promising. Given this new challenge for anesthesiologists, we decided to review current trends in the perioperative management of patients receiving isolated intestinal transplants, the main complications that arise, treatment strategies, and future prospects.

Medication adherence in patients who undergo cardiac transplantation.

BACKGROUND: Heart transplant patients are required to take medication for life, both immunosuppressants to prevent rejection and any required for other illnesses. Treatment compliance can be measured quantitatively or qualitatively. Compliance measurement is not easy owing to different factors. The aim of this study was to assess the prevalence of therapeutic compliance in heart transplant patients. METHODS: We undertook a cross-sectional observational descriptive study. The sample comprised patients who received a heart transplant from 2001 to 2011. Of the 203 patients in total, we studied 99. We used the Morisky-Green test as an indirect method and recorded the immunosuppressant blood levels as a direct method. RESULTS: The mean age of the patients was 50 ± 12 years, and 84% were male. According to the Morisky-Green test, 33% of the patients were noncompliant, of whom 30% said they rarely forgot to take their medication. Patients took an average of 8 ± 3 drugs per day, but only 85% knew what the drugs were for; 24% of the patients had grade 3A rejection, and 65% had graft vessel disease. CONCLUSIONS: Transplanted patients in this study showed a high level of therapeutic adherence that did not differ from other transplant series, either cardiac or other organs, nor from other chronic diseases. The results for defaulters were higher than that expected from these patients. The defaulter results were expected to be lower, given the information that the patients were supposed to have, both before and after the transplantation, and with the strict medical monitoring. Therefore, we have to stress therapeutic compliance, both medical and dietary-hygiene measures, and seek new strategies to improve the results.