Transdiaphragmatic intercostal hernia induced by sternutation: A case report.

INTRODUCTION AND IMPORTANCE: Sternutation is, by definition, a situation that increases abdominal pressure. However, it has not been clearly linked to protrusion of abdominal content through weaknesses in the abdominal boundaries. CASE PRESENTATION: Here we present a case report in which the only trigger factor found for an abdominal content protrusion was a sternutation episode. The patient arrived in our institution with the diagnosis of a transdiaphragmatic intercostal hernia, proven in CT-scan. He was, then, submitted to emergent surgery, where through thoracotomy and subcostal laparotomy, hernia content was reduced. The patient had a favorable evolution. CLINICAL DISCUSSION: TDIH is a rare entity, for which there are still no consensus regarding its management. This makes clinical practice more challenging, leaving to the surgeon the therapeutic decision tailored to each patient. CONCLUSION: This entity should be further studied, and consensus reached regarding its management.

The Role of TOMM40 in Cardiovascular Mortality and Conduction Disorders: An Observational Study.

Aims: TOMM40 single nucleotide polymorphism (SNP) rs2075650 consists of allelic variation c.275-31A > G and it has been linked to Alzheimer disease, apolipoprotein and cholesterol levels and other risk factors. However, data on its role in cardiovascular disorders are lacking. The first aim of the study is to evaluate mortality according to TOMM40 genotype in a cohort of selected patients affected by advanced atherosclerosis. Second aim was to investigate the relationship between Xg and AA alleles and the presence of conduction disorders and implantation of defibrillator (ICD) or pacemaker (PM) in our cohort. Materials and Methods: We enrolled 276 patients (mean age 70.16 ± 7.96 years) affected by hemodynamic significant carotid stenosis and/or ischemia of the lower limbs of II or III stadium Fontaine. We divided the population into two groups according to the genotype (Xg and AA carriers). We evaluated several electrocardiographic and echocardiographic parameters, including heart rate, rhythm, presence of right and left bundle branch block (LBBB and RBBB), PR interval, QRS duration and morphology, QTc interval, and left ventricular ejection fraction (LVEF). We clinically followed these patients for 82.53 ± 30.02 months and we evaluated the incidence of cardiovascular events, number of deaths and PM/ICD implantations. Results: We did not find a difference in total mortality between Xg and AA carriers (16.3 % vs. 19.4%; p = 0.62). However, we found a higher mortality for fatal cardiovascular events in Xg carriers (8.2% vs. 4.4%; HR = 4.53, 95% CI 1.179-17.367; p = 0.04) with respect to AA carriers. We noted a higher percentage of LBBB in Xg carriers (10.2% vs. 3.1%, p = 0.027), which was statistically significant. Presence of right bundle branch block (RBBB) was also higher in Xg (10.2% vs. 4.4%, p = 0.10), but without reaching statistically significant difference compared to AA patients. We did not observe significant differences in heart rate, presence of sinus rhythm, number of device implantations, PR and QTc intervals, QRS duration and LVEF between the two groups. At the time of enrolment, we observed a tendency for device implant in Xg carriers at a younger age compared to AA carriers (58.50 ± 0.71 y vs. 72.14 ± 11.11 y, p = 0.10). During the follow-up, we noted no statistical difference for new device implantations in Xg respect to AA carriers (8.2% vs. 3.5%; HR = 2.384, 95% CI 0.718-7.922; p = 0.156). The tendency to implant Xg at a younger age compared to AA patients was confirmed during follow-up, but without reaching a significant difference(69.50 ± 2.89 y vs. 75.63 ± 8.35 y, p = 0.074). Finally, we pointed out that Xg carriers underwent device implantation 7.27 ± 4.43 years before AA (65.83 ± 6.11 years vs. 73.10 ± 10.39 years) and that difference reached a statistically significant difference (p = 0.049) when we considered all patients, from enrollment to follow-up. Conclusions: In our study we observed that TOMM40 Xg patients affected by advanced atherosclerosis have a higher incidence of developing fatal cardiovascular events, higher incidence of LBBB and an earlier age of PM or ICD implantations, as compared to AA carriers. Further studies will be needed to evaluate the genomic contribution of TOMM40 SNPs to cardiovascular deaths and cardiac conduction diseases.

Absceso hepático en Cali, Colombia / Liver abscess in Cali, Colombia

INTRODUCCIÓN: El absceso hepático (AH) es el tipo mas común de abscesos viscerales. Se estima que el perfil epidemiológico de esta enfermedad ha cambiado con el aumento de la resistencia de los microorganismos y el uso de nuevos medicamentos. OBJETIVO: Describir las características demográficas y clínicas de los pacientes hospitalizados con diagnóstico de AH en un hospital universitario del suroccidente colombiano. MÉTODOS: Se realizó un estudio observacional retrospectivo, en la Fundación Valle del Lili, Cali, Colombia. Se incluyeron pacientes mayores de 18 años con diagnóstico de AH hospitalizados entre 2011-2020. RESULTADOS: Se incluyeron 182 pacientes. La mediana de edad fUe 56 años (rango intercuartílico, 45-67) y 62,1% fueron hombres. El microrganismo mas común fue Klebsiella pneumoniae (17,6%). La mayoría requirió drenaje percutáneo (58,2%). El 58,8% tuvo un absceso único y 54,4% fue manejado en cuidados intensivos. El 7,1% de los pacientes falleció. Al comparar los casos que fueron manejados en cuidados intensivos vs. aquellos que no lo fueron, hubo más hepatomegalia (28,3 vs. 11,0%, p = 0,004), derrame pleural derecho (48,5 vs. 28,1%, p = 0,010), cirugía (42,4 vs. 13,4%, p < 0,001), falla terapéutica (22,2 vs. 7,3%, p = 0,007) y muerte (12,1 vs. 1,2%, p = 0,005) en los atendidos en UCI. CONCLUSIÓN: Las Enterobacterales son la principal causa de AH en nuestra población. La mortalidad ha disminuido, pero la hospitalización en cuidados intensivos sigue siendo alta.

BACKGROUND: Liver abscess (LA) is the most common type of visceral abscess. It is estimated that the epidemiological profile of this disease has changed with the increase in resistance and the use of new drugs. AIM: To describe the demographic and clinical characteristics of hospitalized patients with a diagnosis of LA in a university hospital in the southwestern region of Colombia. METHODS: A. retrospective observational study was conducted at Fundación Valle del Lili, Cali, Colombia. Patients older than 18 years with a diagnosis of LA hospitalized between 2011-2020 were included. RESULTS: A total of 182 patients were included. The median age was 56 years (interquartile range, 45-67) and 62.1% were men. The most common microorganism was Klebsiella pneumoniae (17.6%). The majority required percutaneous drainage (58.2%). A 58.8% had a single abscess and 54.4% were treated in ICU. A 7.1% of the patients died. When comparing cases treated in the ICU vs. those who did not, there was more hepatomegaly (28.3 vs. 11.0%, p = 0.004), right pleural effusion (48.5 vs. 28.1%, p = 0.010), surgery (42.4 vs. 13.4%, p < 0.001), therapeutic failure (22.2 vs. 7.3%, p = 0.007) and death (12.1 vs. 1.2%, p = 0.005) in patients treated in ICU. CONCLUSION: Enterobacterales are the main cause of LA in our population. Mortality has decreased, but intensive care hospitalization remains high.

Comparison of the accuracy of four diagnostic prediction rules for pulmonary embolism in patients admitted to the emergency department.

INTRODUCTION AND OBJECTIVES: Ruling out pulmonary embolism (PE) through a combination of clinical assessment and D-dimer level can potentially avoid excessive use of computed tomography pulmonary angiography (CTPA). We aimed to compare the diagnostic accuracy of the standard approach based on the Wells and Geneva scores combined with a standard D-dimer cut-off (500 ng/ml), with three alternative strategies (age-adjusted and the YEARS and PEGeD algorithms) in patients admitted to the emergency department (ED) with suspected PE. METHODS: Consecutive outpatients admitted to the ED who underwent CTPA due to suspected PE were retrospectively assessed. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and diagnostic odds ratios were calculated and compared between the different diagnostic prediction rules. RESULTS: We included 1402 patients (mean age 69±18 years, 54% female), and PE was confirmed in 25%. Compared to the standard approach (p<0.001), an age-adjusted strategy increased specificity with a non-significant decrease in sensitivity only in patients older than 70 years. Compared to the standard and age-adjusted approaches, the YEARS and PEGeD algorithms had the highest specificity across all ages, but were associated with a significant decrease in sensitivity (p<0.001), particularly in patients aged under 60 years (sensitivity of 81% in patients aged between 51 and 60 years). CONCLUSION: Compared to the standard approach, all algorithms were associated with increased specificity. The age-adjusted strategy was the only one not associated with a significant decrease in sensitivity compared to the standard approach, enabling CTPA requests to be reduced safely.

Association between Ustekinumab Trough Levels, Serum IL-22, and Oncostatin M Levels and Clinical and Biochemical Outcomes in Patients with Crohn's Disease.

Background: Ustekinumab (UST) has demonstrated effectiveness in treating patients with Crohn's disease. Monitoring treatment response can improve disease management and reduce healthcare costs. We investigated whether UST trough levels (TLs), serum IL22, and Oncostatin M (OSM) levels could be early indicators of non-response by analysing their correlation with clinical and biochemical outcomes in CD. Methods: Patients with CD initiating UST treatment from October 2018 to September 2020 were enrolled at six Italian centres for inflammatory bowel disease (IBD). Clinical and biochemical data were collected at four time points: baseline, second subcutaneous (SC) dose, fourth SC dose, and 52 weeks. TLs were measured during maintenance, at the second SC dose, and at the fourth SC dose. IL-22 and OSM serum levels were assessed at baseline and the second SC dose. We analysed whether TLs, IL22 levels, and OSM serum levels were associated with clinical response, clinical remission, biochemical remission, and endoscopic remission using the appropriate statistical tests. Results: Out of eighty-four initially enrolled patients, five were lost to follow-up, and eleven discontinued the drug before 52 weeks. At the 52-week time point, 47% achieved biochemical remission based on faecal calprotectin levels, and 61.8% achieved clinical remission. TLs at the second SC dose significantly correlated with biochemical remission at the same time point (p = 0.011). However, TLs did not correlate with clinical remission. Baseline OSM levels did not correlate with biochemical or clinical remission or response. IL22 levels notably decreased during UST therapy (p = 0.000), but its values did not correlate with biochemical or clinical remission. Conclusions: UST is an effective therapy for patients with CD. TLs measured at the second SC dose significantly correlated with biochemical remission, emphasising their potential role in treatment monitoring. Levels of OSM and IL-22, despite a significant decrease in the latter during therapy, did not exhibit correlations with clinical or biochemical outcomes in our study. Further studies are needed to confirm these findings.

Hemorrhagic Cerebrovascular Disease: An Unusual Presentation of Hyperhomocysteinemia / Accidente cerebrovascular hemorrágico: una inusual presentación de hiperhomocisteinemia / Acidente vascular cerebral hemorrágico: uma apresentação incomum da hiper-homocisteinemia

Introduction: Stroke is a major cause of morbidity and mortality worldwide, with hemorrhagic stroke being the deadliest form of acute stroke. Therefore, the cause of the event should be determined to direct the associated therapy and take preventive measures. Hyperhomocysteinemia has been described as a rare etiology of stroke. Although hyperhomocysteinemia has been associated with venous thrombotic events, altered endothelial function, and procoagulant states, its clinical role in stroke remains controversial. Case description: We present a case of a 60-year-old male patient with primary autoimmune hypothyroidism who presented with dysarthria, facial paresis, and left upper-limb monoparesis after sexual intercourse. A simple skull computed tomography scan showed hyperintensity in the right basal ganglion, indicating an acute hemorrhagic event. Etiological studies were performed, including ambulatory blood pressure monitoring, cerebral angiography, and transthoracic echocardiogram, which ruled out underlying vascular pathology. During follow-up, vitamin B12 deficiency and hyperhomocysteinemia were detected, without other blood biochemical profile alterations. Supplementation was initiated, and homocysteine levels gradually decreased, without new neurological deficits observed during follow-up. Conclusion: Quantification of homocysteine should be considered in patients with a cerebrovascular disease without apparent cause, as documenting hyperhomocysteinemia and correcting its underlying etiology are essential not only for providing appropriate management but also for preventing future events.

Introducción: el accidente cerebrovascular es una causa importante de morbilidad y mortalidad en todo el mundo, y el accidente cerebrovascular hemorrágico es la forma más mortífera de accidente cerebro- vascular agudo. La determinación de la causa del evento es esencial para dirigir la terapia asociada y poder tomar medidas preventivas. La hiperhomocisteinemia se ha descrito como una etiología poco frecuente de accidente cerebrovascular. Aunque esta se ha asociado con eventos trombóticos venosos, disfunción endotelial alterada y estados procoagulantes, sigue siendo controvertido su papel clínico en el accidente cerebrovascular. Descripción del caso: se presenta el caso de un hombre de 60 años con hipotiroidismo autoinmune primario que presentó disartria, paresia facial y monoparesia del miembro superior izquierdo después de un encuentro sexual. Una simple tomografía computarizada de cráneo mostró hipointensidad en la región del ganglio basal derecho, que indicaba un evento hemorrágico agudo. Se realizaron estudios etiológicos, incluyendo monitorización ambulatoria de la presión arterial, angiografía cerebral y ecocardiograma transtorácico, que descartaron patología vascular subyacente. Durante el seguimiento, se detectó deficiencia de vitamina B12 e hiperhomocisteinemia, sin otras alteraciones en el perfil bioquímico sanguíneo. Se inició la suplementación y los niveles de homocisteína disminuyeron gradualmente, sin observar nuevos déficits neurológicos durante el seguimiento. Conclusión: la cuantificación de homocisteína debe ser considerada en casos de enfermedad cerebrovascular sin causa aparente, dado que documentar la hiperhomocisteinemia y corregir su etiología subyacente es esencial no solo para proporcionar un manejo adecuado, sino también para prevenir eventos futuros.

Introdução: o acidente vascular cerebral (AVC) é uma das principais causas de morbidade e mortalidade em todo o mundo, sendo o AVC hemorrágico a forma mais letal de AVC agudo. A determinação da causa do evento é essencial para direcionar a terapia associada e poder tomar medidas preventivas. A hiperhomocisteinemia tem sido descrita como uma etiologia rara de acidente vascular cerebral. Embora a hiper-homocisteinemia tenha sido associada a eventos trombóticos venosos, disfunção endotelial alterada e estados pró-coagulantes, seu papel clínico no AVC permanece controverso. Descrição do caso: apresentamos o caso de um homem de 60 anos com hipotireoidismo autoimune primário que apresentou disartria, paresia facial e monoparesia do membro superior esquerdo após relação sexual. A tomografia computadorizada de crânio mostrou hipointensidade na região do gânglio da base direito, indicando evento hemorrágico agudo. Foram realizados estudos etiológicos, incluindo monitorização ambulatorial da pressão arterial, angiografia cerebral e ecocardiograma transtorácico, que descartaram patologia vascular subjacente. Durante o acompanhamento, foram detectados deficiência de vitamina B12 e hiper-homocistei- nemia, sem outras alterações no perfil bioquímico sanguíneo. A suplementação foi iniciada e os níveis de homocisteína diminuíram gradualmente, sem novos déficits neurológicos observados durante o acompanhamento. Conclusão: a quantificação da homocisteína deve ser considerada em casos de doença vascular cerebral sem causa aparente, pois documentar a hiper-homocisteinemia e corrigir sua etiologia subjacente é essencial não apenas para fornecer manejo adequado, mas também para prevenir eventos futuros.

Involvement of APOE in Incidence of Revascularization in Patients Affected by Peripheral Arterial Disease: A Prospective Study from Southern Italy.

INTRODUCTION: Atherosclerosis is a complex multifactorial disease and apolipoprotein E (APOE) polymorphism has been associated with cardiovascular events. The APOE gene, located on chromosome 19q13.2, has an important role in lipid metabolism, in particular on circulating cholesterol levels, implying further pleiotropic effects; from its polymorphism are derived three alleles (ε2, ε3 and ε4), which induce different phenotypes, while its impact on carotid and femoral atherosclerosis is still controversial. OBJECTIVES: The aim of the study is to investigate the relationship between APOE genotypes and peripheral revascularization in a cohort of patients affected by advanced peripheral arterial disease (PAD) at a prolonged follow-up. MATERIALS AND METHODS: Some 332 patients (259 males and 73 females; mean age 70.86 ± 7.95 years) with severe PAD were enrolled in a longitudinal study, with a 90.75 ± 32.25 month follow-up, assessing major adverse cardiovascular events (MACE). RESULTS: As compared with ε3/ε3, in ε4 patients we observed a significant higher incidence of carotid (13.2% vs. 5.6%; HR = 2.485, 95% CI 1.062-5.814; p = 0.036) and lower limb (11.8% vs. 4.3%; HR = 2.765, 95% CI 1.091-7.008; p = 0.032) revascularizations and, accordingly, a higher incidence of total peripheral revascularizations (13.5% vs. 9.5%; HR = 2.705, 95% CI 1.420-5.151; p = 0.002). HR remained statistically significant even when adjusted for classic cardiovascular risk factors. CONCLUSIONS: In our observational study, we confirm that the ε4 allele is associated with higher total peripheral revascularization in patients with advanced atherosclerotic vascular disease at prolonged follow-up.

Analysis of neutropenia as a predictive factor of the efficacy of trifluridine-tipiracil treatment.

OBJECTIVES: Trifluridine-tipiracil (TAS-102), an oral cytotoxic agent used in adult patients with refractory metastatic colorectal cancer (mCRC), has been associated with neutropenia (chemotherapy-induced neutropenia) (CIN)). MATERIALS AND METHODS: We evaluated the efficacy and safety of TAS-102 in a group of 45 mCRC patients (median age 66 years) in Huelva province, Spain, in a retrospective, multicenter observational study. RESULTS: We showed that the association between TAS-102 and CIN can be used as a predictor of efficacy. 20% (9/45) of patients with an Eastern Cooperative Oncology Group (ECOG) score of 2 had received at least one previous chemotherapy treatment. Overall, 75.5% (34/45) and 28.9% (13/45) had received anti-VEGF and anti-EGFR monoclonal antibodies, respectively. Additionally, 80% (36/45) of patients had received third-line treatment. The mean treatment period, duration of overall survival (OS), and duration of progression-free survival (PFS) were 3.4, 12, and 4 months, respectively. A partial response was seen in 2 patients (4.3%), and disease stabilization was observed in 10 patients (21.3%). Neutropenia was the most frequent grade 3 - 4 toxicity (46.7%; 21/45). Other findings were anemia (77.8%; 35/45), all grades of neutropenia (73.3%; 33/45), and gastrointestinal toxicity (53.3%; 24/45). The dose of TAS-102 needed to be reduced in 68.9% (31/45) of patients, whereas treatment needed to be interrupted in 80% (36/45) of patients. Grade 3 - 4 neutropenia was a positive prognostic factor for OS (p = 0.023). CONCLUSION: A retrospective evaluation shows that grade 3 - 4 neutropenia is an independent predictor of treatment response and survival in patients undergoing routine treatment for mCRC, but this finding needs confirmation in a prospective study.

Vedolizumab is superior to infliximab in biologic naïve patients with ulcerative colitis.

There are no prospective, head-to-head, controlled trials comparing the efficacy and safety of Infliximab (IFX) and Vedolizumab (VDZ) for the treatment of moderate-to-severe ulcerative colitis (UC), while only a few real-life retrospective studies have been published so far. We assessed the efficacy of IFX vs. VDZ in two cohorts of biologic-naïve outpatients with moderate-to-severe UC or mild, but refractory, disease. Data were extracted from patients' files and reviewed. The duration of follow-up (FU) was 52 weeks. The primary endpoint was the clinical remission (CR) at the end of FU. Secondary endpoints were: drug persistency, time to obtain CR, clinical response at the end of the induction phase (IP), steroid-free CR (compared to patients who used steroids at baseline) at the end of FU, need for drug optimization, adverse events (AEs), and normalization of C-reactive protein (CRP). We also analyzed the causes of dropping out (primary non-response), or secondary loss of response (immunogenic or not), for each group. We enrolled 82 patients (50 IFX and 32 VDZ) who met the inclusion criteria. At the end of FU, CR was obtained in 32% of the patients on IFX and 75% on VDZ (p = 0.0003). Drug persistency was superior for VDZ compared to IFX (78% vs. 52%, p = 0.033). Clinical response at the end of induction was reached in 54% and in 81% in the IFX and VDZ group, respectively (p = 0.014). Steroid-free clinical remission at the end of FU was 62% and 94% in the IFX vs. VDZ group, respectively (p = 0.036). The need for drug optimization was higher for VDZ than for IFX (28% vs. 57%, p = 0.009), while the time to obtain CR, the incidence of AEs, mean duration of FU, and rate of CRP normalization at the end of IP were comparable between the two groups. There was a prevalence of patients dropping out because of primary non-response in IFX group (p = 0.027), while the incidence of secondary loss of response was similar in the two groups. At the multivariate analysis, CRP and Partial Mayo Score (PMS) at T0 did not correlate with CR at the end of FU in both groups. In this retrospective, real world data study in biologic-naïve patients, VDZ was superior to IFX in CR, clinical response rate at the end of IP, drug persistency, steroid-free remission, and need for optimization at the end of FU.

Analysis of Blood Biochemistry and Pituitary-Gonadal Histology after Chronic Exposure to Bisphenol-A of Mice.

Bisphenol-A is an emerging pollutant that is widespread in the environment, and to which live beings are continuously and inadvertently exposed. It is a substance with an endocrine-disrupting capacity, causing alterations in the reproductive, immunological, and neurological systems, among others, as well as metabolic alterations. Our study aimed to assess its clinical signs, and effects on the most relevant blood biochemical parameters, and to evaluate pituitary and gonadal histology after a chronic exposure of adult mice to different BPA doses (0.5, 2, 4, 50 and 100 µg/kg BW/day) through their drinking water. The biochemical results showed that a marked significant reduction (p < 0.05) was produced in the levels of serum glucose, hypoproteinaemia and hypoalbuminemia in the groups exposed to the highest doses, whereas in the group exposed to 50 µg/kg BW/day the glucose and total protein levels dropped, and the animals exposed to 100 µg/kg BW/day experienced a diminution in albumin levels. In the case of the group exposed to 50 µg/kg BW/day, however, hypertriglyceridemia and hypercholesterolemia were determined, and the blood parameters indicating kidney alterations such as urea and creatinine experienced a significant increase (p < 0.05) with respect to the controls. Regarding the pituitary and gonads, none of the animals exposed presented histological alterations at the doses tested, giving similar images to those of the control group. These results suggest that continuous exposure to low BPA doses could trigger an inhibition of hepatic gluconeogenesis, which would result in a hypoglycaemic state, together with an induction of the enzymes responsible for lipidic synthesis, a mechanism by which the increase in the lipid and serum cholesterol levels could be explained. Likewise, the decline in the protein and albumin levels would be indicative of a possible hepatic alteration, and the increase in urea and creatinine would point to a possible renal perturbation, derived from continuous exposure to this xenobiotic. Based on our results, it could be said that chronic exposure to low BPA doses would not produce any clinical signs or histological pituitary-gonadal effects, but it could cause modifications in some blood biochemical parameters, that could initially indicate a possible hepatic and renal effect.

Endophytic fungi from kale (Brassica oleracea var. acephala) modify roots-glucosinolate profile and promote plant growth in cultivated Brassica species. First description of Pyrenophora gallaeciana.

Endophytic fungi of crops can promote plant growth through various mechanisms of action (i.e., improve nutrient uptake and nutrient use efficiency, and produce and modulate plant hormones). The genus Brassica includes important horticultural crops, which have been little studied in their interaction with endophytic fungi. Previously, four endophytic fungi were isolated from kale roots (Brassica oleracea var. acephala), with different benefits for their host, including plant growth promotion, cold tolerance, and induction of resistance to pathogens (Xanthomonas campestris) and pests (Mamestra brassicae). In the present work, the molecular and morphological identification of the four different isolates were carried out, describing them as the species Acrocalymma vagum, Setophoma terrestris, Fusarium oxysporum, and the new species Pyrenophora gallaeciana. In addition, using a representative crop of each Brassica U's triangle species and various in vitro biochemical tests, the ability of these fungi to promote plant growth was described. In this sense, the four fungi used promoted the growth of B. rapa, B. napus, B. nigra, B. juncea, and B. carinata, possibly due to the production of auxins, siderophores, P solubilization or cellulase, xylanase or amylase activity. Finally, the differences in root colonization between the four endophytic fungi and two pathogens (Leptosphaeria maculans and Sclerotinia sclerotiorum) and the root glucosinolate profile were studied, at different times. In this way, how the presence of progoitrin in the roots reduces their colonization by endophytic and pathogenic fungi was determined, while the possible hydrolysis of sinigrin to fungicidal products controls the colonization of endophytic fungi, but not of pathogens.

The Impact of Depression on the Functional Outcome of the Elderly Stroke Victim from a Gender Perspective: A Systematic Review.

(1) Background: The aim of this systematic review focused on analyzing the impact of depression on the functional outcome of the elderly stroke victim and how this disorder affects both the female and the male population. (2) Methods: We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review was registered in PROSPERO (ID 346284). The systematic search for clinical trials was performed in the databases Pubmed, Otseeker, Scopus, Web of Science, Psycinfo, Medline Complete, ScienceDirect, SciELO, and Dialnet. Articles were selected according to the inclusion and exclusion criteria, including those dealing with post-stroke depression in adults whose psychological status had changed. Studies that only assessed the psychological state of caregivers were excluded. (3) Results: In total, 609 articles were identified, of which 11 randomized controlled trials were finally included in the review. The results indicate that post-stroke depression influences the recovery of functionality and quality of life. In addition, the need to detect the mood of the adult population after the stroke and to provide individualized treatment according to the characteristics of the person is highlighted. (4) Conclusions: This systematic review shows how early detection of post-stroke depressive symptoms can improve the degree of disability and quality of life of the person, especially in women.

Adrenal Neuroblastoma Producing Catecholamines Diagnosed in Adults: Case Report.

Neuroblastoma is a solid tumor considered almost exclusively pediatric, with more than 95% of patients diagnosed before 10 years of age, with a mostly benign clinical course and with encouraging survival rates in these age ranges. It occurs rarely in adolescents, and the presentation in young adults or older people is even rarer; consequently, a more severe prognosis and higher mortality rates have been documented within this population. This is also due to a great limitation within the treatment since the chemotherapeutic regimens proposed so far are valid for pediatric patients, with low tolerance to it within the adult population. We present the case of a 24-year-old female patient with catecholamine-secreting neuroblastoma who obtained surgical management, with subsequent local tumor recurrence, with subsequent need for onco-specific and symptomatic management.

Fungal endophytes of Brassicaceae: Molecular interactions and crop benefits.

Brassicaceae family includes an important group of plants of great scientific interest, e.g., the model plant Arabidopsis thaliana, and of economic interest, such as crops of the genus Brassica (Brassica oleracea, Brassica napus, Brassica rapa, etc.). This group of plants is characterized by the synthesis and accumulation in their tissues of secondary metabolites called glucosinolates (GSLs), sulfur-containing compounds mainly involved in plant defense against pathogens and pests. Brassicaceae plants are among the 30% of plant species that cannot establish optimal associations with mycorrhizal hosts (together with other plant families such as Proteaceae, Chenopodiaceae, and Caryophyllaceae), and GSLs could be involved in this evolutionary process of non-interaction. However, this group of plants can establish beneficial interactions with endophytic fungi, which requires a reduction of defensive responses by the host plant and/or an evasion, tolerance, or suppression of plant defenses by the fungus. Although much remains to be known about the mechanisms involved in the Brassicaceae-endophyte fungal interaction, several cases have been described, in which the fungi need to interfere with the GSL synthesis and hydrolysis in the host plant, or even directly degrade GSLs before they are hydrolyzed to antifungal isothiocyanates. Once the Brassicaceae-endophyte fungus symbiosis is formed, the host plant can obtain important benefits from an agricultural point of view, such as plant growth promotion and increase in yield and quality, increased tolerance to abiotic stresses, and direct and indirect control of plant pests and diseases. This review compiles the studies on the interaction between endophytic fungi and Brassicaceae plants, discussing the mechanisms involved in the success of the symbiosis, together with the benefits obtained by these plants. Due to their unique characteristics, the family Brassicaceae can be seen as a fruitful source of novel beneficial endophytes with applications to crops, as well as to generate new models of study that allow us to better understand the interactions of these amazing fungi with plants.

Italian Case Report with a Double Mutation in PSEN1 (K311R and E318G).

Alzheimer's disease (AD) is the most common cause of dementia worldwide. The clinical spectrum of suspected AD has been extended from mild cognitive impairment (MCI) to preclinical AD which includes people who have typical cognitive function but harbor the underlying biological features of AD. We report the first case of an Italian patient affected by MCI (MMSE 24\30), characterized by a double mutation p.Lys311Arg (K311R) and p.Glu318Gly (E318G) in Presenilin-1 but with the absence of abnormal accumulation of amyloid beta.

Depressive risk among Italian socioeconomically disadvantaged children and adolescents during COVID-19 pandemic: a cross-sectional online survey.

BACKGROUND: Children and adolescents and low-income individuals are considered particularly vulnerable for mental health implications during the current COVID-19 pandemic. Depression is a frequent negative emotional response during an epidemic outbreak and is also prone importantly to environmental risk like stressors derived from income inequality. We aimed to assess depressive symptomatology in a sample of Italian low-income minors during the COVID-19 outbreak. We hypothesized that the stronger were the negative effects of the pandemic on socioeconomic conditions, the higher would have been the risk for showing depressive symptoms. METHODS: We performed a cross-sectional study during July 2020, at the end of the Italian first wave of COVID-19 pandemic. We recruited 109 Italian socioeconomically disadvantaged children and adolescents from 7 to 17 years. We used an online survey to collect socio-demographic and clinical data and information about pandemic-related stressors and to assess depressive symptoms with the Children's Depression Inventory 2 (CDI 2), Parent Version (Emotional Problems subscale) and Self-Report Short Form. We performed logistic regression analysis to assess the association between depressive symptoms and potential risk factors for mental health. RESULTS: 22% and 14% of participants showed depressive symptoms at the CDI 2 Parent Version and Self-Report, respectively. Participants coming from families experiencing a lack of basic supplies during the pandemic (34.9%) were more expected to show depressive symptoms at CDI 2 Parent Version. Participants with a pre-existing neuropsychiatric diagnosis (26.6%) were more likely to exhibit depressive symptoms measured by CDI 2 Parent Version. CONCLUSIONS: The results of our study showed that a group of Italian socioeconomically disadvantaged children and adolescents were more vulnerable to depressive symptoms if they suffered from a paucity of essential supplies during the pandemic or had pre-existing neurodevelopmental disorders. The promotion of educational and child-care programs and activities could be crucial in sustaining the prevention of mental distress in those frail subjects who particularly need support outside the family. Further studies are needed to detect effective preventive and therapeutic strategies to adopt promptly in the case of another pandemic wave.

Comparison of 5 acute pulmonary embolism mortality risk scores in patients with COVID-19.

OBJECTIVE: Pulmonary embolism (PE) is a common complication of SARS-CoV-2 infection. We aimed to explore the short-term outcomes among patients with acute PE and COVID-19 and to further determine and compare the performance of the different prognostic scores (PESI, sPESI, BOVA, FAST and ESC scores) for risk-stratification in this scenario. METHODS: Retrospective single-centre study of 85 patients with SARS-CoV-2 infection and PE admitted to the Emergency Department (ED). The diagnostic accuracy of each above-mentioned prognostic score was calculated post hoc, and their discriminative power was evaluated through an AUC curve. RESULTS: Among the 85 patients, all-cause death occurred within 7 days for 6 patients (7.1%) and within 30 days for 14 patients (16.5%). Despite being older and having a higher percentage of altered mental status on presentation, non-survivors patients did not differ from survivors regarding comorbidities, traditional risk factors for venous thromboembolism and signs and symptoms at the ED presentation.Each risk stratification tool had modest discriminative power for 7-day mortality (AUC range, 0.601-0.730) with slightly lower discrimination for 30-day mortality (AUC range, 0.543-0.638). The pair-wise comparison of ROC curves showed that PESI had better predictive value for short-term mortality than ESC score (z test = 3.92, p = 0.001) and sPESI (z test = 2.43, p = 0.015); there is no significant difference between PESI and BOVA score (z test = 1.05, p = 0.295) and FAST score (z test = 0.986, p = 0.324). CONCLUSION: The most common risk-stratification tools for PE had modest discriminative power to predict short-term mortality in patients with acute PE and COVID-19.

Depletion of mitochondrial methionine adenosyltransferase α1 triggers mitochondrial dysfunction in alcohol-associated liver disease.

MATα1 catalyzes the synthesis of S-adenosylmethionine, the principal biological methyl donor. Lower MATα1 activity and mitochondrial dysfunction occur in alcohol-associated liver disease. Besides cytosol and nucleus, MATα1 also targets the mitochondria of hepatocytes to regulate their function. Here, we show that mitochondrial MATα1 is selectively depleted in alcohol-associated liver disease through a mechanism that involves the isomerase PIN1 and the kinase CK2. Alcohol activates CK2, which phosphorylates MATα1 at Ser114 facilitating interaction with PIN1, thereby inhibiting its mitochondrial localization. Blocking PIN1-MATα1 interaction increased mitochondrial MATα1 levels and protected against alcohol-induced mitochondrial dysfunction and fat accumulation. Normally, MATα1 interacts with mitochondrial proteins involved in TCA cycle, oxidative phosphorylation, and fatty acid ß-oxidation. Preserving mitochondrial MATα1 content correlates with higher methylation and expression of mitochondrial proteins. Our study demonstrates a role of CK2 and PIN1 in reducing mitochondrial MATα1 content leading to mitochondrial dysfunction in alcohol-associated liver disease.

Prognostic Accuracy of the Modified CHA2DS2-VASc Score in COVID-19 Patients Admitted to the Emergency Department Due to Clinical Worsening.

INTRODUCTION: Risk factors comprising the CHA2DS2VASc score are recognized as risk factors for venous thromboembolism and mortality in COVID-19 patients. A modified CHA2DS2VASc score (M-CHA2D2VASc), developed by changing gender criteria from female to male, has been proposed to predict in-hospital mortality in COVID-19 patients. The aim of this study was to evaluate the prognostic accuracy of M-CHA2D2VASc for adverse clinical outcomes and short-term mortality in COVID-19 patients admitted to the Emergency Department. MATERIAL AND METHODS: Retrospective study of patients admitted to the ED who underwent computed tomography pulmonary angiography due to suspected pulmonary embolism or clinical worsening. Patients were stratified into three M-CHA2DS2-VASc risk-categories: low (0 - 1 points), intermediate (2 - 3 points) and high-risk (≥ 4 points). RESULTS: We included 300 patients (median age 71 years, 59% male). The overall mortality was 27%. The M-CHA2DS2-VASc score was higher in non-survivors compared to survivors [4 (IQR:3 - 5) vs 2 (IQR: 1 - 4), respectively, p < 0.001). The M-CHA2DS2-VASc score was identified as an independent predictor of mortality in a multivariable logistic regression model (OR 1.406, p = 0.007). The Kaplan-Meier survival curves showed that the M-CHA2DS2-VASc score was associated with short-term mortality (log-rank test < 0.001), regardless of hospitalization (log-rank test p < 0.001 and p = 0.007, respectively). The survival proportion was 92%, 80% and 63% in the lower, intermediate, and higher risk-groups. As for the risk-categories, no difference was found in pulmonary embolism, Intensive Care Unit admission, and invasive mechanical ventilation. DISCUSSION: This is the first study to validate M-CHA2DS2-VASc score as a predictor of short-term mortality in patients admitted to the Emergency Department. CONCLUSION: The M-CHA2DS2-VASC score might be useful for prompt risk-stratification in COVID-19 patients during admission to the Emergency Department.

Introdução: O score CHA2DS2VASc engloba variáveis reconhecidas como fatores de risco para tromboembolismo venoso e mortalidade nos doentes com COVID-19. O score CHA2DS2VASc modificado (M-CHA2DS2-VASc), criado pela alteração do critério de género de feminino para masculino, foi proposto como preditor da mortalidade intra-hospitalar nestes doentes. O objetivo deste trabalho foi avaliar o valor prognóstico do M-CHA2DS2-VASc como preditor de eventos adversos e mortalidade a curto-prazo nos doentes com COVID-19 admitidos no Serviço de Urgência. Material e Métodos: Análise retrospetiva de doentes admitidos no Serviço de Urgência que realizaram tomografia computorizada pulmonar com administração de contraste por agravamento clínico e/ou suspeita de embolia pulmonar. Definiram-se três categorias de risco M-CHA2DS2-VASc: baixo, intermédio e alto (0 - 1; 2 - 3 e ≥ 4 pontos, respectivamente). Resultados: Incluíram-se 300 doentes (idade mediana: 71 anos, 59% homens). A mortalidade global foi 27%. O M-CHA2DS2-VASc foi maior em não sobreviventes [4 (IQR: 3 - 5) vs 2 (IQR: 1 - 4), p < 0,001) e constituiu um preditor independente de mortalidade numa análise multiparamétrica (OR: 1.406, p = 0,007). As curvas de sobrevivência demonstraram a associação do M-CHA2DS2-VASc com a mortalidade a curto-prazo (log-rank test < 0,001), independentemente dos doentes serem hospitalizados ou não (log-rank test p < 0,001 e p = 0,007, respetivamente). A taxa de sobrevida foi de 92%, 80% e 63% nos grupos de baixo, intermédio e alto risco. De acordo com as categorias de risco, não foram encontradas diferenças na incidência de embolia pulmonar, admissão em Cuidados Intensivos e ventilação mecânica invasiva. Discussão: Este é o primeiro estudo a validar o M-CHA2DS2-VASc como preditor de mortalidade a curto prazo na admissão no Serviço de Urgência. Conclusão: O M-CHA2DS2-VASc pode ser útil para estratificação de risco nos doentes com COVID-19 admitidos no Serviço de Urgência.

Treating the N0 neck in early stage oral cancer: a pause for re-assessment?

The incidence of metastases following neck dissection in the apparent lymph node negative neck in oral cancer is between 7% and 33%; early resection of cervical metastases may well increase survival. Modern imaging techniques can reduce the yield of previously undiagnosed metastatic nodes in elective neck dissection (END). An audit of 112 consecutive cases was conducted to determine the proportion of undiagnosed nodal metastases, after END. There were neck metastases in 10 cases (9%), which were mainly (but not all) micrometastic. The 20% likelihood of nodal metastases was only apparent in primary tumours greater than 6 mm thick. The length of inpatient stay was increased from 3.7 to 16.5 days with free vascularised transfer. There were complications including cranial nerve damage. There were two peri-operative deaths. No ipsilateral neck failures occurred, median follow up was 937 days. To reduce unnecessary END, resection can be undertaken as a prior procedure, subsequently only carrying out END on tumours greater than 6 mm, or with unfavourable tumour characteristics.