Publications by authors named "Laura Fernandez"

145 Publications

Re-staging and follow-up of rectal cancer patients with MR imaging when "Watch-and-Wait" is an option: a practical guide.

Insights Imaging 2021 Aug 9;12(1):114. Epub 2021 Aug 9.

Radiology Department, Champalimaud Foundation, Avenida Brasília, 1400-038, Lisbon, Portugal.

In the past nearly 20 years, organ-sparing when no apparent viable tumour is present after neoadjuvant therapy has taken an increasingly relevant role in the therapeutic management of locally-advanced rectal cancer patients. The decision to include a patient or not in a "Watch-and-Wait" program relies mainly on endoscopic assessment by skilled surgeons, and MR imaging by experienced radiologists. Strict surveillance using the same modalities is required, given the chance of a local regrowth is of approximately 25-30%, almost always surgically salvageable if caught early. Local regrowths occur at the endoluminal aspect of the primary tumour bed in almost 90% of patients, but the rest are deep within it or outside the rectal wall, in which case detection relies solely on MR Imaging. In this educational review, we provide a practical guide for radiologists who are, or intend to be, involved in the re-staging and follow-up of rectal cancer patients in institutions with an established "Watch-and-Wait" program. First, we discuss patient preparation and MR imaging acquisition technique. Second, we focus on the re-staging MR imaging examination and review the imaging findings that allow us to assess response. Third, we focus on follow-up assessments of patients who defer surgery and confer about the early signs that may indicate a sustained/non-sustained complete response, a rectal/extra-rectal regrowth, and the particular prognosis of the "near-complete" responders. Finally, we discuss our proposed report template.
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http://dx.doi.org/10.1186/s13244-021-01055-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353037PMC
August 2021

Papillary Thyroid Carcinoma in Ectopic Thyroid Tissue Within a Suspected Cervical Paraganglioma.

Clin Nucl Med 2021 Jul 26. Epub 2021 Jul 26.

From the Department of Endocrinology and Nutrition Pathological Anatomy Service, Gregorio Marañón General University Hospital, Madrid, Spain.

Abstract: Ectopic differentiated thyroid carcinoma represents less than 1% of all thyroid carcinoma cases, which usually arises along the cervical midline, and (delving into literature) there are scarce reports of such entity in nuclear medicine imaging studies. We present a rare case of a confirmed synchronous, orthotopic, and heterotopic (in lateral ectopic thyroid tissue) differentiated thyroid carcinoma in a patient who was previously misdiagnosed as having a cervical paraganglioma, based on compatible clinical, analytical, and imagenological (both structural and functional) findings.
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http://dx.doi.org/10.1097/RLU.0000000000003827DOI Listing
July 2021

Elective minimally invasive surgery for sigmoid diverticulitis: operative outcomes of patients with complicated versus uncomplicated disease.

Colorectal Dis 2021 Jul 26. Epub 2021 Jul 26.

Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, Florida, USA.

Aim: The aim of this work was to compare the results of elective minimally invasive surgery between patients with complicated sigmoid diverticulitis and those with uncomplicated disease.

Method: An institutional review board-approved database was searched for all consecutive patients who underwent elective minimally invasive surgery, including laparoscopic, hand-assisted and robotic sigmoidectomy, for diverticulitis between 2010 and 2017; they were classified according to the modified Hinchey classification as having complicated (abscess, fistula, stricture, obstruction, bleeding or previous perforation) versus uncomplicated disease. Data recorded included baseline demographics, indications for surgery, operative details and complications.

Results: Three hundred and twenty-five patients underwent elective sigmoidectomy for complicated (n = 105) and uncomplicated (n = 220) diverticulitis. Surgical indications for complicated disease were abscess (n = 74), stricture (n = 14), fistula (n = 28) and bleeding (n = 7). The two groups were statistically comparable for age, gender, body mass index and American Society of Anesthesiologists score. Patients with complicated disease had higher rates of concomitant loop ileostomy creation (9.5% vs. 0.9%, p < 0.001) and synchronous resections (9.5% vs. 2.7%, p = 0.01), higher volumes of blood loss (177 ± 140 vs. 125 ± 92 ml, p < 0.001), longer length of stay (5.6 ± 3 vs. 4.8 ± 2 days, p = 0.04) and longer operating time (218.2 ± 59 vs. 185.8 ± 63 min, p < 0.001). There were no significant differences in anastomotic leakage (3% vs. 1%, p = 0.3), conversion to laparotomy (4.8% vs. 2.3%, p = 0.3) or overall complications (36% vs. 25.9%, p = 0.06) for complicated versus uncomplicated disease, respectively.

Conclusion: Minimally invasive surgery for complicated diverticulitis resulted in higher rates of construction of proximal ileostomy and synchronous resections and longer operating times and length of hospital stay. Otherwise, it has outcomes that are not significantly different from the results recorded in patients with uncomplicated disease.
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http://dx.doi.org/10.1111/codi.15837DOI Listing
July 2021

Atomically-Precise Texturing of Hexagonal Boron Nitride Nanostripes.

Adv Sci (Weinh) 2021 Sep 22;8(17):e2101455. Epub 2021 Jul 22.

Centro de Física de Materiales CSIC/UPV-EHU-Materials Physics Center, San Sebastián, E-20018, Spain.

Monolayer hexagonal boron nitride (hBN) is attracting considerable attention because of its potential applications in areas such as nano- and opto-electronics, quantum optics and nanomagnetism. However, the implementation of such functional hBN demands precise lateral nanostructuration and integration with other two-dimensional materials, and hence, novel routes of synthesis beyond exfoliation. Here, a disruptive approach is demonstrated, namely, imprinting the lateral pattern of an atomically stepped one-dimensional template into a hBN monolayer. Specifically, hBN is epitaxially grown on vicinal Rhodium (Rh) surfaces using a Rh curved crystal for a systematic exploration, which produces a periodically textured, nanostriped hBN carpet that coats Rh(111)-oriented terraces and lattice-matched Rh(337) facets with tunable width. The electronic structure reveals a nanoscale periodic modulation of the hBN atomic potential that leads to an effective lateral semiconductor multi-stripe. The potential of such atomically thin hBN heterostructure for future applications is discussed.
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http://dx.doi.org/10.1002/advs.202101455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425884PMC
September 2021

Rescue Angioplasty in Subclavian Artery After Percutaneous Closure Device Failure in an Inadvertent Misplacement of A Central Venous Line.

Heart Views 2021 Jan-Mar;22(1):76-78. Epub 2021 Apr 22.

Division of Cardiology, Coronary Care Unit, Joan XXIII University Hospital, IISPV, Rovira I Virgili University, Tarragona, Spain.

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http://dx.doi.org/10.4103/HEARTVIEWS.HEARTVIEWS_83_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254160PMC
April 2021

Exchange catalysis by tapasin exploits conserved and allele-specific features of MHC-I molecules.

Nat Commun 2021 07 9;12(1):4236. Epub 2021 Jul 9.

Laboratory of Protein Biochemistry, Institute for Chemistry & Biochemistry, Freie Universität Berlin, Berlin, Germany.

The repertoire of peptides presented by major histocompatibility complex class I (MHC-I) molecules on the cell surface is tailored by the ER-resident peptide loading complex (PLC), which contains the exchange catalyst tapasin. Tapasin stabilizes MHC-I molecules and promotes the formation of stable peptide-MHC-I (pMHC-I) complexes that serve as T cell antigens. Exchange of suboptimal by high-affinity ligands is catalyzed by tapasin, but the underlying mechanism is still elusive. Here we analyze the tapasin-induced changes in MHC-I dynamics, and find the catalyst to exploit two essential features of MHC-I. First, tapasin recognizes a conserved allosteric site underneath the α-helix of MHC-I, 'loosening' the MHC-I F-pocket region that accomodates the C-terminus of the peptide. Second, the scoop loop of tapasin relies on residue L18 to target the MHC-I F-pocket, enabling peptide exchange. Meanwhile, tapasin residue K16 plays an accessory role in catalysis of MHC-I allotypes bearing an acidic F-pocket. Thus, our results provide an explanation for the observed allele-specificity of catalyzed peptide exchange.
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http://dx.doi.org/10.1038/s41467-021-24401-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271027PMC
July 2021

Cortico-autonomic local arousals and heightened somatosensory arousability during NREMS of mice in neuropathic pain.

Elife 2021 07 6;10. Epub 2021 Jul 6.

Department of Fundamental Neurosciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.

Frequent nightly arousals typical for sleep disorders cause daytime fatigue and present health risks. As such arousals are often short, partial, or occur locally within the brain, reliable characterization in rodent models of sleep disorders and in human patients is challenging. We found that the EEG spectral composition of non-rapid eye movement sleep (NREMS) in healthy mice shows an infraslow (~50 s) interval over which microarousals appear preferentially. NREMS could hence be vulnerable to abnormal arousals on this time scale. Chronic pain is well-known to disrupt sleep. In the spared nerve injury (SNI) mouse model of chronic neuropathic pain, we found more numerous local cortical arousals accompanied by heart rate increases in hindlimb primary somatosensory, but not in prelimbic, cortices, although sleep macroarchitecture appeared unaltered. Closed-loop mechanovibrational stimulation further revealed higher sensory arousability. Chronic pain thus preserved conventional sleep measures but resulted in elevated spontaneous and evoked arousability. We develop a novel moment-to-moment probing of NREMS vulnerability and propose that chronic pain-induced sleep complaints arise from perturbed arousability.
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http://dx.doi.org/10.7554/eLife.65835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291975PMC
July 2021

Temporal preparation in adults with autistic spectrum disorder: The variable foreperiod effect.

Autism Res 2021 Jul 5. Epub 2021 Jul 5.

Ecole Normale Supérieure, PSL Research University, Département d'études cognitives, Institut Jean Nicod, CNRS UMR 8129, Paris, France.

Research suggested the possibility that temporal cognition may be different in autistic spectrum disorder (ASD). Although there are some empirical studies examining timing ability in these individuals, to our knowledge, no one directly assessed the ability to predict when an event will occur. Here, we report a study on implicit temporal preparation in individuals with ASD as indexed by the variable foreperiod (FP) effect. We compared a group of adult ASD participants to a group of typically-developed (TD) controls, for their respective abilities to utilize implicit temporal information in a simple detection task with three different preparatory intervals (FP, short, middle and long). Participants were given a warning tone to signal an imminent stimulus, and asked to press a key as quickly as they could upon detection of the stimulus. Both groups were able to use implicit temporal information, as revealed by both the variable-FP effect (i.e., faster response for targets appearing after a long FP) and asymmetric sequential effects (i.e., slower response in short-FP trials following a previous long-FP trial). The TD group exhibited a faster response in a long-FP trial that was preceded by short-FP one, whereas the ASD group did not, as reflected in their higher percentage of response omissions for a target that appeared later than in the previous trial. The reduced ability of ASD participants to modulate their responses under these conditions might reflect a difficulty in time-based monitoring of stimulus occurrence. LAY SUMMARY: Time-processing may be different in autistic spectrum disorder (ASD). This study addressed the ability to anticipate a relevant stimulus's onset according to predictable interstimulus intervals comparing adults with ASD and typically developed controls. We found that ASD participants did not benefit from temporal preparation when stimulus appeared later than previously attended. This suggests a reduced ability in detecting implicit temporal regularities between events.
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http://dx.doi.org/10.1002/aur.2573DOI Listing
July 2021

Growth impairment, increased placental glucose uptake and altered transplacental transport in VIP deficient pregnancies: Maternal vs. placental contributions.

Biochim Biophys Acta Mol Basis Dis 2021 Oct 26;1867(10):166207. Epub 2021 Jun 26.

Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN-CONICET), Laboratorio de Inmunofarmacología, Facultad de Ciencias Exactas y Naturales (FCEN-UBA), Buenos Aires, Argentina. Electronic address:

Glucose uptake by the placenta and its transfer to the fetus is a finely regulated process required for placental and fetal development. Deficient placentation is associated with pregnancy complications such as fetal growth restriction (FGR). The vasoactive intestinal peptide (VIP) has embryotrophic effects in mice and regulates human cytotrophoblast metabolism and function. Here we compared glucose uptake and transplacental transport in vivo by VIP-deficient placentas from normal or VIP-deficient maternal background. The role of endogenous VIP in placental glucose and amino acid uptake was also investigated. Wild type C57BL/6 (WT) or VIP (VIP HT) females were mated with WT, VIP knock-out (VIP KO) or VIP HT males. Glucose uptake and transplacental transport were evaluated by the injection of the fluorescent d-glucose analogue 2-NBDG in pregnant mice at gestational day (gd) 17.5. Glucose and amino acid uptake in vitro by placental explants were measured with 2-NBDG or C-MeAIB respectively. In normal VIP maternal background, fetal weight was reduced in association with placental VIP deficiency, whereas placental weight was unaltered. Paradoxically, VIP placentas presented higher glucose uptake and higher gene expression of GLUT1 and mTOR than VIP placentas. However, in a maternal VIP-deficient environment placental uptake and transplacental transport of glucose increased while fetal weights were unaffected, regardless of feto-placental genotype. Results point to VIP-deficient pregnancy in a normal background as a suitable FGR model with increased placental glucose uptake and transplacental transport. The apparently compensatory actions are unable to sustain normal fetal growth and could result in complications later in life.
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http://dx.doi.org/10.1016/j.bbadis.2021.166207DOI Listing
October 2021

The Authors Reply.

Dis Colon Rectum 2021 05;64(5):e97-e98

Champalimaud Foundation, Lisbon, Portugal Angelita & Joaquim Gama Institute, University of São Paulo School of Medicine, Colorectal Surgery Division, Sao Paulo, Brazil Angelita & Joaquim Gama Institute, Sao Paulo, Brazil Champalimaud Foundation, Lisbon, Portugal Angelita & Joaquim Gama Institute, Sao Paulo, Brazil Champalimaud Foundation, Lisbon, Portugal Angelita & Joaquim Gama Institute, University of São Paulo School of Medicine, Colorectal Surgery Division, Ludwig Institute for Cancer Research São Paulo Branch, Sao Paulo, Brazil.

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http://dx.doi.org/10.1097/DCR.0000000000002003DOI Listing
May 2021

Biographies of international women leaders in neurosurgery.

Neurosurg Focus 2021 03;50(3):E19

21Department of Neurosurgery, Wayne State University School of Medicine, Detroit.

We received so many biographies of women neurosurgery leaders for this issue that only a selection could be condensed here. In all of them, the essence of a leader shines through. Many are included as "first" of their country or color or other achievement. All of them are included as outstanding-in clinical, academic, and organized neurosurgery. Two defining features are tenacity and service. When faced with shocking discrimination, or numbing indifference, they ignored it or fought valiantly. When choosing their life's work, they chose service, often of the most neglected-those with pain, trauma, and disability. These women inspire and point the way to a time when the term "women leaders" as an exception is unnecessary.-Katharine J. Drummond, MD, on behalf of this month's topic editors.
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http://dx.doi.org/10.3171/2021.1.FOCUS201096DOI Listing
March 2021

Understanding the natural selection of human embryos: blastocyst quality modulates the inflammatory response during the peri-implantation period.

Am J Reprod Immunol 2021 Mar 25:e13423. Epub 2021 Mar 25.

CONICET, Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina.

Problem: Decidualized cells display an active role during embryo implantation sensing blastocyst quality, allowing the implantation of normal developed blastocysts and preventing the invasion of impaired developed ones. Here, we characterized the immune microenvironment generated by decidualized cells in response to soluble factors secreted by blastocysts that shape the receptive milieu.

Method Of Study: We used an in vitro model of decidualization based on the Human Endometrial Stromal Cells line (HESC) differentiated with medroxiprogesterone and dibutyryl-cAMP, then treated with human blastocysts-conditioned media (BCM) classified according to their quality.

Results: Decidualized cells treated with BCM from impaired developed blastocysts increased IL-1β production. Next, we evaluated the ability of decidualized cells to modulate other mediators associated with menstruation as chemokines. Decidualized cells responded to stimulation with BCM from impaired developed blastocysts increasing CXCL12 expression and CXCL8 secretion. The modulation of these markers was associated with the recruitment and activation of neutrophils, while regulatory T cells recruitment was restrained. These changes were not observed in the presence of BCM from normal developed blastocysts.

Conclusion: Soluble factors released by impaired developed blastocysts induce an exacerbated inflammatory response associated with neutrophils recruitment and activation, providing new clues to understand the molecular basis of the embryo-endometrial dialogue.
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http://dx.doi.org/10.1111/aji.13423DOI Listing
March 2021

Botanical Control of Citrus Green Mold and Peach Brown Rot on Fruits Assays Using a Phytochemically Characterized Extract.

Plants (Basel) 2021 Feb 24;10(3). Epub 2021 Feb 24.

Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario S2002LRK, Argentina.

(Polygonaceae) is a perennial herb that grows in the central area of Argentina and it is commonly used by native populations to heal infected wounds and other conditions related to fungal infections. In this article, we explored the antifungal activity of its ethyl acetate extract against a panel of three fruit phytopathogenic fungi including: , and . The sesquiterpenes isolated from the extract were also evaluated against these strains, demonstrating that the dialdehyde polygodial was the responsible for this activity. In order to encourage the use of the extract rather than the pure compound, we displayed assays using fresh oranges and peaches inoculated with and , respectively, and subsequently treated by immersion with an extract solution of 250 and 62.5 µg/mL, respectively. There were no statistically significant differences between the treatments with commercial fungicides and the extract over the control of both fruit rots. The concentration of the active compound present in the extract used on fruit experiments was determined by Gas Chromatography-Mass Spectroscopy. Finally, cytotoxicity evaluation against Huh7 cells showed that extract was less cytotoxic than the commercial fungicides at the assayed concentrations. After these findings we could conclude that a chemically characterized extract of should be further developed to treat fungal diseases in fruits from an agro-ecological model.
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http://dx.doi.org/10.3390/plants10030425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996193PMC
February 2021

Traumatic Subarachnoid Hemorrhage: A Scoping Review.

J Neurotrauma 2021 Apr 22. Epub 2021 Apr 22.

NIHR Global Health Research Group on Neurotrauma, University of Cambridge, Cambridge, United Kingdom.

Sixty-nine million people have a traumatic brain injury (TBI) each year, and TBI is the most common cause of subarachnoid hemorrhage (SAH). Traumatic SAH (TSAH) has been described as an adverse prognostic factor leading to progressive neurological deterioration and increased morbidity and mortality. A limited number of studies, however, evaluate recent trends in the diagnosis and management of SAH in the context of trauma. The objective of this scoping review was to understand the extent and type of evidence concerning the diagnostic criteria and management of TSAH. This scoping review was conducted following the Joanna Briggs Institute methodology for scoping reviews. The review included adults with SAH secondary to trauma, where isolated TSAH (iTSAH) refers to the presence of SAH in the absence of any other traumatic radiographic intracranial pathology, and TSAH refers to the presence of SAH with the possibility or presence of additional traumatic radiographic intracranial pathology. Data extracted from each study included study aim, country, methodology, population characteristics, outcome measures, a summary of findings, and future directives. Thirty studies met inclusion criteria. Studies were grouped into five categories by topic: TSAH associated with mild TBI (mTBI),  = 13), and severe TBI ( = 3); clinical management and diagnosis ( = 9); imaging ( = 3); and aneurysmal TSAH ( = 1). Of the 30 studies, two came from a low- and middle-income country (LMIC), excluding China, nearly a high-income country. Patients with TSAH associated with mTBI have a very low risk of clinical deterioration and surgical intervention and should be treated conservatively when considering intensive care unit admission. The Helsinki and Stockholm computed tomography scoring systems, in addition to the American Injury Scale, creatinine level, age decision tree, may be valuable tools to use when predicting outcome and death.
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http://dx.doi.org/10.1089/neu.2021.0007DOI Listing
April 2021

Materials Applications of Aptamers.

ACS Appl Mater Interfaces 2021 03 18;13(8):9289-9290. Epub 2021 Feb 18.

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http://dx.doi.org/10.1021/acsami.1c02475DOI Listing
March 2021

In Vitro Antifungal Screening of Argentine Native or Naturalized Plants against the Phytopathogen Monilinia fructicola.

Comb Chem High Throughput Screen 2021 Jan 20. Epub 2021 Jan 20.

ICiAgro Litoral, Universidad Nacional del Litoral, CONICET, Facultad de Ciencias Agrarias, Kreder 2805, Esperanza, 3080HOF. Argentina.

Background: One of the main problems that fruit health has gone through in recent years is the difficult eradication of their fungal pathogens during crops or the post-harvest stage. This concerns the whole world because it represents huge production losses, fruit export restrictions and consumer distrust. Consequently, new alternatives are sought to avoid the increasing use of fungicides that cause important damage to fruit consumers and to the environment. One of the alternatives to solve this problem could be the exploration of plants and their active compounds applied to the treatment of fruit health.

Materials And Methods: This article describes peach production worldwide and particularly in Argentina, in addition to the main fungal rot that causes the greatest economic losses. Furthermore, experimental in-vitro studies of 69 extracts obtained from 18 plants growing in the central region of Argentina were displayed against the devastating fungus Monilinia fructicola, which greatly affects stone fruits. A simple and effective method developed in agar plate was applied to evaluate a large number of samples in a short time.

Results: Results showed that approximately 36% of the samples tested were strongly active against this pathogen, 12% were moderately active and 52% demonstrated to be inactive.

Conclusion: These findings support the possible use of natural products for fruit health and the importance of deepening in this field of science.
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http://dx.doi.org/10.2174/1386207324666210121113648DOI Listing
January 2021

Conditional recurrence-free survival of clinical complete responders managed by watch and wait after neoadjuvant chemoradiotherapy for rectal cancer in the International Watch & Wait Database: a retrospective, international, multicentre registry study.

Lancet Oncol 2021 01 11;22(1):43-50. Epub 2020 Dec 11.

Department of Colorectal Surgery, Angelita and Joaquim Gama Institute, São Paulo, Brazil; Department of Surgical Oncology, Hospital Beneficencia Portuguesa, São Paulo, Brazil; Hospital Alemão Oswaldo Cruz, São Paulo, Brazil; Ludwig Institute for Cancer Research, São Paulo Branch, São Paulo, Brazil. Electronic address:

Background: Watch and wait is a novel management strategy in patients with rectal cancer who have a clinical complete response after neoadjuvant chemoradiotherapy. Surveillance of these patients is generally intensive, because local regrowth (with the potential for salvage) occurs in 25% of patients, and distant metastases occur in 10% of patients. It is unclear for how long these patients should be followed up. To address this issue, we did conditional survival modelling using the International Watch & Wait Database (IWWD), which is a large-scale registry of patients with a clinical complete response after neoadjuvant chemotherapy who have been managed by a watch-and-wait strategy.

Methods: We did a retrospective, multicentre registry study using a dataset from the IWWD, which includes data from 47 clinics across 15 countries. We selected patients (aged ≥18 years) with rectal cancer who had a clinical complete response after neoadjuvant chemotherapy, and who were subsequently managed by a watch-and-wait strategy between Nov 25, 1991, and Dec 31, 2015. Patients who had not achieved a clinical complete response or who had undergone any surgical procedure were excluded. The criteria used for defining a clinical complete response and the specific surveillance strategies were at the discretion of each participating centre. We used conditional survival modelling to estimate the probability of patients remaining free of local regrowth or distant metastasis for an additional 2 years after sustaining a clinical complete response or being distant metastasis-free for 1, 3, and 5 years from the date of the decision to commence watch and wait. The primary outcomes were conditional local regrowth-free survival at 3 years, and conditional distant metastasis-free survival at 5 years.

Findings: We identified 793 patients in the IWWD with clinical complete response who had been managed by a watch-and-wait strategy. Median follow-up was 55·2 months (IQR 36·0-75·6). The probability of remaining free from local regrowth for an additional 2 years if a patient had a sustained clinical complete response for 1 year was 88·1% (95% CI 85·8-90·9), for 3 years was 97·3% (95·2-98·6), and for 5 years was 98·6% (97·6-100·0). The probably of remaining free from distant metastasis for a further 2 years in patients who had a clinical complete response without distant metastasis for 1 year was 93·8% (92·3-95·9), for 3 years was 97·8% (96·6-99·3), and for 5 years was 96·6% (94·0-98·9).

Interpretation: These results suggest that the intensity of active surveillance in patients with rectal cancer managed by a watch-and-wait approach could be reduced if they achieve and maintain a clinical complete response within the first 3 years of starting this approach.

Funding: European Registration of Cancer Care, financed by the European Society of Surgical Oncology, the Champalimaud Foundation Lisbon, the Bas Mulder Award, granted by the Alpe d'HuZes Foundation and the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre.
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http://dx.doi.org/10.1016/S1470-2045(20)30557-XDOI Listing
January 2021

Decidual factors and vasoactive intestinal peptide guide monocytes to higher migration, efferocytosis and wound healing in term human pregnancy.

Acta Physiol (Oxf) 2021 05 4;232(1):e13579. Epub 2020 Dec 4.

Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química Biológica de la Factultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina.

Aim: To explore the functional profile of circulating monocytes and decidual macrophages at term human pregnancy and their contribution to tissue repair upon stimulation ex vivo with decidual factors and the vasoactive intestinal peptide (VIP).

Methods: Peripheral blood monocytes were isolated from pregnant and non-pregnant volunteers and tested in vitro with decidual explants from term placenta and VIP. The effect of VIP on decidual explants and the effect of its conditioned media on monocytes or decidual macrophages isolated by magnetic beads was carried out by RT-qPCR and ELISA for cytokines expression and release. Migration assays were performed in transwell systems. Efferocytosis was assessed in monocytes or decidual macrophages with CFSE-labelled autologous apoptotic neutrophils and quantified by flow cytometry. Monocyte and decidual macrophages wound healing capacity was evaluated using human endometrial stromal cell monolayers. Immunohistochemistry was performed in serial tissue sections of different placentas.

Results: VIP is expressed in the villi as well as in trophoblast giant cells distributed within the decidua of term placenta. VIP induced the expression of antiinflmammatory markers and monocyte chemoattractant CCL2 and CCL3 in decidual tissues. Monocytes presented higher migration towards decidual explants than CD4 and CD8 cells. VIP-conditioned monocytes displayed an enhanced efferocytosis and wound healing capacity comparable to that of decidual macrophages. Moreover limited efferocytosis of pregnant women monocytes was restored by VIP-induced decidual factors.

Conclusion: Results show the conditioning of monocytes by decidual factors and VIP to sustain processes required for tissue repair and homeostasis maintenance in term placenta.
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http://dx.doi.org/10.1111/apha.13579DOI Listing
May 2021

Safety and efficacy of coronary laser ablation as an adjunctive therapy in percutaneous coronary intervention: a single-centre experience.

Coron Artery Dis 2021 May;32(3):241-246

Interventional Cardiology Unit, Cardiology Division, Joan XXIII university hospital, Universitat Rovira Virgili, Tarragona, Spain.

Background: Coronary laser is a long-established coadjuvant therapy in interventional cardiology. This study aimed to present our experience regarding the safety and efficacy of laser assistance to percutaneous coronary intervention (PCI) in different scenarios of coronary artery disease.

Methods: We used coronary laser as an adjunctive therapy for PCI between May 2014 and March 2020. The safety of laser ablation was evaluated by studying any complication associated with the laser application. Besides, the laser contribution to PCI and 1 year of follow-up for adverse cardiac events was studied.

Results: Coronary laser was performed in 81 lesions and 75 patients in different scenarios to assist PCI. The average age was 66 ± 11.7 years and 72 (88.9%) were men. Coronary laser was used in 30 (37%) cases for in-stent-material debulking; 26 (32.1%) in primary angioplasty, 19 (23.4%) in chronic total occlusion and 5 (6.2%) in saphenous vein grafts. Procedural success was achieved in 77 (95.1%) with 1 (1.2%) type III coronary perforation. One year of follow-up for combined adverse cardiac events consisting of death due to any cause, myocardial infarction or target vessel failure showed an event-free rate of 0.82 (95% confidence interval, 0.72-0.91).

Conclusions: Our preliminary experience reveals the safety and efficacy of the current modality of coronary laser as a coadjuvant therapy in PCI with a low rate of adverse cardiac events in 1-year of follow-up. Further studies are needed to establish more precisely the contribution of laser application in different contexts of coronary artery disease.
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http://dx.doi.org/10.1097/MCA.0000000000000989DOI Listing
May 2021

Nonoperative Management for T2 Low Rectal Cancer: A Western Approach.

Clin Colon Rectal Surg 2020 Nov 2;33(6):366-371. Epub 2020 Nov 2.

Angelita & Joaquim Gama Institute, São Paulo, Brazil.

The possibility of organ preservation in early rectal cancer has gained popularity during recent years. Patients with early tumor stage and low risk for local recurrence do not usually require neoadjuvant chemoradiation for oncological reasons. However, these patients may be considered for chemoradiation exclusively for the purpose of achieving a complete clinical response and avoid total mesorectal excision. In addition, cT2 tumors may be more likely to develop complete response to neoadjuvant therapy and may constitute ideal candidates for organ-preserving strategies. In the setting where the use of chemoradiation is exclusively used to avoid major surgery, one should consider maximizing tumor response. In this article, we will focus on the rationale, indications, and outcomes of patients with early rectal cancer being treated by neoadjuvant chemoradiation to achieve organ preservation by avoiding total mesorectal excision.
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http://dx.doi.org/10.1055/s-0040-1714241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605908PMC
November 2020

High-flow nasal oxygen reduces endotracheal intubation: a randomized clinical trial.

Ther Adv Respir Dis 2020 Jan-Dec;14:1753466620956459

Intensive Care Unit, University Hospital La Princesa, Madrid, Spain.

Background: The benefits of high-flow nasal cannula (HFNC) as primary intervention in patients with acute hypoxemic respiratory failure (AHRF) are still a matter in debate. Our objective was to compare HFNC therapy conventional oxygen therapy (COT) in the prevention of endotracheal intubation in this group of patients.

Methods: An open-label, controlled and single-centre clinical trial was conducted in patients with severe AHRF, defined by a PaO/FIO ratio ⩽200, to compare HFNC with a control group (CG) treated by COT delivered through a face mask, with the need to perform intubation as the primary outcome. The secondary outcomes included tolerance of the HFNC device and to look for the predictive factors for intubation in these patients.

Results: A total of 46 patients were included (22 in the COT group and 24 in the HFNC group) 48% of whom needed intubation: 63% in the COT group and 33% in the HFNC group, with significant differences both in intention to treat [χ = 4.2;  = 0.04, relative risk (RR) = 0.5; confidence interval (CI) 95%: 0.3-1.0] and also in treatment analysis (χ = 4.7;  = 0.03; RR = 0.5; IC 95%: 0.3-0.9) We obtained a number needed to treat (NNT) = 3 patients treated to avoid an intubation. Intubation occurred significantly later in the HFNC group. Estimated PaO/FIO, respiratory rate and dyspnea were significantly better in the HFNC group. Patients treated with HFNC who required intubation presented significant worsening after the first 8 h, as compared with non-intubated HFNC group patients. Mortality was 22% with no differences. The HFNC group patients were hospitalized for almost half of the time in the intensive care unit (ICU) and in the ward, with significantly less hospital length of stay. A total of 14 patients in the HFNC group (58%) complained of excessive heat and 17% of noise; 3 patients did not tolerate HFNC.

Conclusion: Patients with severe acute hypoxemic respiratory failure who tolerate HFNC present a significantly lower need for endotracheal intubation compared with conventional oxygen therapy.

Clinical Trial Register: EUDRA CT number: 2012-001671-36
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http://dx.doi.org/10.1177/1753466620956459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522841PMC
September 2021

Decidualization Process Induces Maternal Monocytes to Tolerogenic IL-10-Producing Dendritic Cells (DC-10).

Front Immunol 2020 18;11:1571. Epub 2020 Aug 18.

CONICET, Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina.

Decidualization is a process that involves phenotypic and functional changes of endometrial stromal cells to sustain endometrial receptivity and the participation of immunoregulatory factors to maintain immune homeostasis. In this context, tolerogenic dendritic cells (DCs) can induce regulatory T cells, which are essential to manage the pro- to anti-inflammatory transition during embryo implantation. Recently, Myeloid Regulatory Cells (MRCs) were proposed as immunosuppressants and tolerance-inducer cells, including the DC-10 subset. This novel and distinctive subset has the ability to produce IL-10 and to induce type 1 regulatory T cells (Tr1) through an HLA-G pathway. Here we focus on the impact of the decidualization process in conditioning peripheral monocytes to MRCs and the DC-10 subset, and their ability to induce regulatory T cells. An model of decidualization with the human endometrial stromal cell line (HESC), decidualized by medroxyprogesterone and dibutyryl-cAMP was used. Monocytes isolated from peripheral blood mononuclear cells from healthy women were cultured with rhGM-CSF + rhIL-4 and then, the effect of conditioned media from decidualized (Dec-CM) and non-decidualized cells (Non-dec-CM) was tested on monocyte cultures. We found that Dec-CM inhibited the differentiation to the CD1aCD14 immature DC profile in a concentration-dependent manner. Dec-CM also significantly increased the frequency of CD83CD86 and HLA-DR cells in the monocyte-derived culture. These markers, associated with the increased production of IL-10, are consistent with a MRCs tolerogenic profile. Interestingly, Dec-CM treatment displayed a higher expression of the characteristic markers of the tolerogenic DC-10 subset, HLA-G and ILT2/CD85j; while this modulation was not observed in cultures treated with Non-dec-CM. Moreover, when monocyte cultures with Dec-CM were challenged with LPS, they sustained a higher IL-10 production and prevented the increase of CD83, CD86, IL-12p70, and TNF-α expression. Finally, the DC-10 subset was able to induce a CD4HLA-G regulatory T cells subset. These results suggest that the decidualization process might induce different subsets of MRCs, like DC-10, able to induce regulatory T cells as a novel CD4HLA-G subset which might play an immunoregulatory role in embryo implantation.
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http://dx.doi.org/10.3389/fimmu.2020.01571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461786PMC
April 2021

Colchicine treatment in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome: A multicenter study in Spain.

Eur J Rheumatol 2020 Sep 18. Epub 2020 Sep 18.

Department of Pediatric Rheumatology, La Paz Children's Hospital, Madrid, Spain.

Objective: To evaluate the efficacy of colchicine therapy in pediatric patients with PFAPA syndrome who present with an incomplete response to the standard treatment or with frequent episodes (an interval of less than 14 days between two disease flares).

Methods: A multicenter cohort study of children diagnosed with PFAPA syndrome and treated with colchicine was performed in three separate hospitals located in Spain. The patients clinical and laboratory data were reviewed by accessing their medical records. Response to colchicine was evaluated after 12 months of treatment for frequency, duration, and intensity of PFAPA episodes.

Results: A total of 13 children were included in our study, 43% of whom were boys. Median age of the colchicine therapy initiation was 6 years (interquartile range (IQR)=3-9.5). Following a 12-month period of colchicine therapy (median dosage of 0.02 mg/kg/day; IQR=0.02-0.03), a significant decrease in the median number of flares (median 8; IQR=7-14 vs 3; IQR=2-4; p=0.005) and the duration of disease episodes (median 4 days; IQR=3.25-5.125 vs 1 day; IQR=1-2; p=0.003) was observed. Furthermore, the highest degree of fever during disease flares was reduced from median 40ºC (IQR=39.5-40) to 38.5ºC (IQR=37.7-38.9) (p=0.002).

Conclusion: Colchicine therapy decreased the frequency and intensity of PFAPA. The use of colchicine could be an effective treatment in pediatric patients with PFAPA syndrome who present with frequent or severe relapses.
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http://dx.doi.org/10.5152/eurjrheum.2020.20102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133885PMC
September 2020

[Corynebacterium pyruviciproducens and Corynebacterium amycolatum mastitis in immunocompetent no breastfeeding women].

Rev Argent Microbiol 2021 Jan-Mar;53(1):39-42. Epub 2020 Jul 25.

Hospital Privado SADIV, Buenos Aires, Argentina.

Corynebacterium species, other than Corynebacterium diphteriae, are usually dismissed as contaminants when recovered from patient's samples. It is often difficult to decide whether these bacteria have clinical relevance or not. The Corynebacterium genus has been implicated in a wide variety of human infections. In this brief report, two cases of mastitis caused by Corynebacterium pyruviciproducens and Corynebacterium amycolatum are described in not breastfeeding women. These patients were immunocompetent with no evidence of ongoing risk factors for mastitis. This report seeks to give importance to this genus by always ranking cultures, starting with a thorough sample collection up until a complete evaluation of lab results and clinical presentation.
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http://dx.doi.org/10.1016/j.ram.2020.06.006DOI Listing
July 2020

Salvage Surgery With Organ Preservation for Patients With Local Regrowth After Watch and Wait: Is It Still Possible?

Dis Colon Rectum 2020 08;63(8):1053-1062

Champalimaud Foundation, Lisbon, Portugal.

Background: Patients with rectal cancer who achieve complete clinical response after neoadjuvant chemoradiation have been managed nonoperatively. Thirty percent of these patients may develop a local regrowth, and salvage resection with radical surgery is usually recommended. However, selected patients could be offered additional organ preservation by local excision. We hypothesized that patients with baseline T2 who underwent neoadjuvant therapy (for the specific purpose of achieving a complete clinical response) were more likely to harbor recurrent disease at an earlier stage and amenable to organ preservation strategies (local excision) when compared with T3/T4 (undergoing neoadjuvant chemoradiation for oncologic reasons).

Objective: The purpose of this study was to compare patients with local regrowth requiring salvage resection according to their baseline stage.

Design: This was a retrospective review of consecutive patients with nonmetastatic distal rectal cancer undergoing neoadjuvant chemoradiation.

Settings: The study included 2 independent tertiary centers with institutional watch-and-wait organ preservation programs.

Patients: Consecutive patients with distal rectal cancer (cT2-4N1-2M0) managed by watch and wait and local regrowth from 2 institutions were included.

Main Outcomes Measures: Final pathologic features and surgical and oncologic outcomes were compared according to baseline staging.

Results: A total of 73 of 257 patients experienced local regrowth. cT2 presented similar to ypT, ypN, R0, and abdominal perineal resection rates (p > 0.05) at the time of salvage when compared with cT3 to cT4. Patients with cT2 at baseline were more likely to undergo an organ preservation procedure for salvage (56.2% vs 26.5%; p = 0.03). Overall and disease-free survival after salvage were similar between groups irrespective of the type of surgery for the regrowth.

Limitations: Retrospective study, small sample size, and possible inaccurate baseline staging.

Conclusions: Although patients with baseline cT2 rectal cancer had similar pathologic stage at the time of recurrence, these patients were more likely to continue an organ preservation pathway after local regrowth through transanal local excision when compared with cT3 to cT4. Despite differences in the use of radical salvage resection, there were no differences in oncologic outcomes. See Video Abstract at http://links.lww.com/DCR/B254. CIRUGÍA DE RESCATE CON PRESERVACIÓN DE ORGANO PARA PACIENTES CON RECIDIVA LOCAL LUEGO DE WATCH & WAIT: ¿SIGUE SIENDO POSIBLE?: Los pacientes con cáncer rectal que logran una respuesta clínica completa luego de la quimiorradiación neoadyuvante han sido tratados de forma no quirúrgica. El treinta por ciento de estos pacientes pueden desarrollar un nuevo crecimiento local y generalmente se recomienda la resección de rescate con cirugía radical. Sin embargo, en pacientes seleccionados se podría ofrecer la posibilidad de preservación de órgano mediante escisión local. Se formuló la hipótesis de que los pacientes con estadio clinico inicial T2 y sometidos a terapia neoadyuvante (con el propósito específico de lograr una respuesta clínica completa) tenían más probabilidades de presentar una recurrencia local en una etapa más temprana y suceptibles de estrategias de preservación de órgano (escisión local) en comparación con T3 / T4 (sometidos a nCRT por razones oncológicas).Comparar los pacientes con recidiva local que requirieron cirugia de rescate de acuerdo con su estadio inicial.Revisión retrospectiva de pacientes consecutivos con cáncer de recto distal no metastásico sometidos a quimiorradiación neoadyuvante.Dos centros terciarios independientes con programas institucionales de preservación de órgano - Watch & Wait.Pacientes consecutivos con cáncer rectal distal (cT2-4N1-2M0) manejados por Watch & Wait y recidiva local.Las características patológicas finales, los resultados quirúrgicos y oncológicos se compararon de acuerdo con la estadificación inicial.Un total de 73 de 257 pacientes presentaron recidiva local. cT2 presentaron similares ypT, ypN, R0 y tasas de resección abdominoperineal (p>0,05) en el momento del rescate en comparación con cT3-4.Los pacientes con cT2 de base tuvieron más probabilidades de someterse a un procedimiento de preservación de órgano durante el rescate (56,2% frente a 26,5%; p = 0,03). Supervivencia general y DFS después del rescate fueron similares entre los grupos, independientemente del tipo de cirugía para la recidiva.Estudio retrospectivo, tamaño de muestra pequeño, la posible estadificación basal inexacta.Aunque los pacientes con cáncer rectal cT2 de base presentaron estadio patologico similar en el momento de la recidiva, estos pacientes tuvieron más probabilidades de continuar una vía de preservación de órgano luego de una recidiva local a través de la escisión local transanal en comparación con cT3-4. A pesar de las diferencias en el uso de la resección radical de rescate, no hubo diferencias en los resultados oncológicos. Consulte Video Resumen en http://links.lww.com/DCR/B254.
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http://dx.doi.org/10.1097/DCR.0000000000001707DOI Listing
August 2020

A Thalamic Reticular Circuit for Head Direction Cell Tuning and Spatial Navigation.

Cell Rep 2020 06;31(10):107747

Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Vaud, Switzerland. Electronic address:

As we navigate in space, external landmarks and internal information guide our movement. Circuit and synaptic mechanisms that integrate these cues with head-direction (HD) signals remain, however, unclear. We identify an excitatory synaptic projection from the presubiculum (PreS) and the multisensory-associative retrosplenial cortex (RSC) to the anterodorsal thalamic reticular nucleus (TRN), so far classically implied in gating sensory information flow. In vitro, projections to TRN involve AMPA/NMDA-type glutamate receptors that initiate TRN cell burst discharge and feedforward inhibition of anterior thalamic nuclei. In vivo, chemogenetic anterodorsal TRN inhibition modulates PreS/RSC-induced anterior thalamic firing dynamics, broadens the tuning of thalamic HD cells, and leads to preferential use of allo- over egocentric search strategies in the Morris water maze. TRN-dependent thalamic inhibition is thus an integral part of limbic navigational circuits wherein it coordinates external sensory and internal HD signals to regulate the choice of search strategies during spatial navigation.
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http://dx.doi.org/10.1016/j.celrep.2020.107747DOI Listing
June 2020

IUI and uterine lavage of in vivo-produced blastocysts for PGT purposes: is it a technically and ethically reasonable perspective? Is it actually needed?

J Assist Reprod Genet 2020 07 26;37(7):1579-1582. Epub 2020 May 26.

Department of Biomedicine and Prevention, Section of Histology and Embryology, University of Rome "Tor Vergata", Rome, Italy.

A recent study by Munné et al. portrayed a protocol to retrieve in vivo produced blastocysts after IUI and uterine lavage for preimplantation genetic testing (PGT) purposes. The authors claimed this protocol might represent a reasonable future perspective for patients who do not want to undergo IVF, but still want to be informed about their embryos' genetic/chromosomal defects. Although the intent of making PGT available also to patients who cannot or do not need to undergo IVF is respectable, the value of this study is undermined by severe technical and ethical issues. Munné and colleagues' paper was discussed within the executive committee (i.e., president and vice-president of the society, director and vice-director of the scientific committee, secretariat, and counselors), the special interest group in reproductive genetics, the scientific committee, and the collegio dei probiviri of the Italian Society of Embryology, Reproduction and Research (SIERR). The points raised from this discussion are summarized in this opinion paper.
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http://dx.doi.org/10.1007/s10815-020-01813-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376991PMC
July 2020

Interleukin-6 as a Biomarker of Early-Onset Neonatal Sepsis.

Am J Perinatol 2021 08 23;38(S 01):e338-e346. Epub 2020 May 23.

Programa de Medicina, Facultad de Salud, Universidad Surcolombiana, Neiva, Huila, Colombia.

Objective: The aim of this study is to determine the utility of C reactive protein (CRP) and interleukin (IL)-6 in the diagnosis of neonatal sepsis (NS) in a neonatal intensive care unit (NICU) in the south of Colombia.

Study Design: A nonmatched case-control study was conducted. Convenience sampling was performed. Data were obtained from clinical records. IL-6 levels were determined using enzyme-linked immunosorbent assay. Receiver operator characteristic (ROC) curve analysis and Youden's index were used to determine the optimal cutoffs for CRP and IL-6 levels in diagnosing NS, early-onset NS (EONS), and late-onset NS (LONS).

Results: Data from 31 cases and 62 controls were included. History of chorioamnionitis (infinite odds ratio [OR] [3.07-infinity]), and the presence of meconium-stained amniotic fluid during birth (OR: 9.04 [1.35-112]) were identified as risk factors for NS. Differences in CRP ( < 0.0001) and IL-6 ( < 0.0485) levels were also found, more significantly for LONS and EONS patients, respectively. In the diagnosis of LONS using CRP levels, the area under the ROC curve (AUC) was 0.8371 ( < 0.0001). The optimal cutoff was 0.53 mg/dL. For EONS diagnosis using IL-6, the AUC was 0.6869 ( = 0.0315) and the optimal cutoff was 17.75 pg/mL.

Conclusion: Differences between CRP and IL-6 levels were found between control and NS groups. Furthermore, CRP showed greater potential diagnostic utility in the LONS group, whereas IL-6 showed greater potential utility in the EONS group.

Key Points: · NS is a major morbimortality cause worldwide. · CRP and IL-6 levels may be useful NS biomarkers. · No biomarker alone is enough for the diagnosis of NS.
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http://dx.doi.org/10.1055/s-0040-1710010DOI Listing
August 2021

Metformin Use in Patients With Rectal Cancer Undergoing Neoadjuvant Chemoradiation: The New Magic Bullet?

Dis Colon Rectum 2020 06;63(6):718-719

Hospital das Clinicas-University of São Paulo School of Medicine Radiology Division, São Paulo, Brazil.

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http://dx.doi.org/10.1097/DCR.0000000000001669DOI Listing
June 2020
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