Intestinal inflammation marker calprotectin regulates epithelial intestinal zinc metabolism and proliferation in mouse jejunal organoids.

Calprotectin (CP), a heterodimer of S100A8 and S100A9, is expressed by neutrophils and a number of innate immune cells and is used widely as a marker of inflammation, particularly intestinal inflammation. CP is a ligand for toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE). In addition, CP can act as a microbial modulatory agent via a mechanism termed nutritional immunity, depending on metal binding, most notably Zn2+. The effects on the intestinal epithelium are largely unknown. In this study we aimed to characterize the effect of calprotectin on mouse jejunal organoids as a model epithelium, focusing on Zn2+ metabolism and cell proliferation. CP addition upregulated the expression of the Zn2+ absorptive transporter Slc39a4 and of methallothionein Mt1 in a Zn2+-sensitive manner, while downregulating the expression of the Zn2+ exporter Slc30a2 and of methallothionein 2 (Mt2). These effects were greatly attenuated with a CP variant lacking the metal binding capacity. Globally, these observations indicate adaptation to low Zn2+ levels. CP had antiproliferative effects and reduced the expression of proliferative and stemness genes in jejunal organoids, effects that were largely independent of Zn2+ chelation. In addition, CP induced apoptosis modestly and modulated antimicrobial gene expression. CP had no effect on epithelial differentiation. Overall, CP exerts modulatory effects in murine jejunal organoids that are in part related to Zn2+ sequestration and partially reproduced in vivo, supporting the validity of mouse jejunal organoids as a model for mouse epithelium.

[Management of patients with lymphatic diseases and lipoedema during the COVID-19 pandemic. Recommendations of the Spanish Group of Lymphology]. / La atención al paciente con patología linfática y lipedema en la pandemia COVID-19. Recomendaciones del Grupo Español de Linfología (GEL).

The COVID-19 pandemic poses a challenge to the management of non-COVID pathologies such as lymphatic diseases and lipoedema. The use of telemedicine can prevent the spread of the disease. A system is needed to help determine the clinical priority and selection of face-to-face or telemedicine options for each patient and how to carry them out during the pandemic. The Spanish Lymphology Group has drafted a consensus document with recommendations based on the literature and clinical experience, as clinical practice guidelines for the management of lymphatic abnormalities and lipoedema during the COVID-19 pandemic. These recommendations must be adapted to the characteristics of each patient, the local conditions of the centres, and the decisions of health care professionals. The document contains minimum criteria, subject to modifications according to the evolution of the pandemic, scientific knowledge and instructions from health authorities.

Author Correction: Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis.

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[Resection of recurrent neck cancers with replacement of the carotid artery]. / Résection des cancers récidivants du cou avec remplacement de l'artère carotide.

OBJECTIVES: The management of patients with recurrent neck cancer invading the carotid artery is controversial. The aim of this study was to evaluate the overall survival and healthy survival years (QALY) as well as the patency of carotid revascularization after enbloc tumor resection followed by complementary radiotherapy. METHODS: From 2000 to 2016, 42 consecutive patients with recurrent neck cancer invading the carotid artery underwent resection of the tumor associated with reconstruction of the carotid artery with a PTFE prosthesis (n=31) or with a saphenous vein graft (n=11). In 11 cases, resection was associated with musculocutaneous flap coverage. The primary tumor was a squamous cell carcinoma of the larynx (20 patients) or of the pharynx (9 patients), undifferentiated carcinoma of unknown origin (10 patients) and anaplastic thyroid carcinoma (3 patients). All patients had postoperative radiotherapy (50-70Gy) supplemented in 16 of them by chemotherapy. Nine patients had metastatic dissemination at the time of reoperation with a recurrent tumor ulcerated to the skin in 5 of them. RESULTS: The combined 30-day mortality and stroke rate was nil. Postoperative morbidity included dysphagia (n=8), vocal cord paralysis (n=6), late wound healing delay (n=2), transient mandibular claudication (n=1) and partial necrosis of the musculocutaneous flap (n=1). No infection and no thrombosis of the bypass were observed during follow-up [median: 31 months, range: 8-167 months]. Twenty-one patients (50%) died from the consequences of the spread of cancer, which had become metastatic, but without local recurrence. The 5-year survival rate was 50.9±8.3%. The median healthy survival year (QALY) was 3.38 [95% CI: 1.70-4.54] with a significant difference between patients without metastasis at the time of reoperation [n=33; QALY=4.02] and those with metastases [n=9; QALY=0.43; P=0.005]. Healthy life expectancy was also significantly longer in patients with laryngeal cancer [n=20, QALY=4.95] compared to patients with other types of tumors [n=22, QALY=1.67; P=0.032]. CONCLUSION: In the absence of metastases, enbloc resection of recurrent neck cancers invading the carotid artery improves the duration and quality of patient survival.

Outcome After Open and Laparoscopic Aortic Surgery in Matched Cohorts Using Propensity Score Matching.

OBJECTIVE/BACKGROUND: To compare the post-operative and mid-term outcomes of laparoscopic aortic surgery with those of conventional aortic surgery performed by a surgical team trained in laparoscopic aortic surgery. METHODS: A prospective study was conducted between January 2006 and December 2011 with 228 consecutive patients having undergone aortic bypass surgery for either an abdominal aortic aneurysm (n = 139) or occlusive aorto-iliac disease (n = 89). Conventional open aortic surgery was carried out in 145 patients, and total laparoscopic repair in 83 patients. The composite primary end point measure grouped together the following adverse events (AEs): (1) any deaths < 30 days or later deaths related to the operation; (2) post-operative hemorrhage necessitating reoperation; (3) myocardial infarction ≤ 30 days; (4) stroke ≤ 30 days; (5) post-operative respiratory failure necessitating re-intubation or assisted ventilation ≥ 4 days; (6) aortic prosthesis infection; (7) aortic prosthesis occlusion; (8) any re-operation related to aortic surgery. In order to diminish bias attributable to the absence of randomization, the two surgical groups were matched by a propensity score enabling analysis of 50 pairs of patients having presented with identical pre-operative characteristics. Univariate analysis of the AE occurring during the first 30 post-operative days was followed by multivariate analysis through logistic regression. The rate of AE during follow up was calculated using the Kaplan-Meier method and the roles of the different co-variables were analyzed using the Cox model. RESULTS: Univariate analysis of the groups adjusted for propensity score showed that laparoscopic repair was associated with a significantly higher risk of AE over the first 30 post-operative days (p = .03). Logistic regression analysis showed that laparoscopic aortic technique (odds ratio [OR] 4.50; p = .01) and coronary artery disease (OR 4.67; p = .02) were independently related to the occurrence of an AE during the post-operative period. The occurrence of AEs during follow up was analyzed using the Cox model. Only two variables, laparoscopic aortic surgery (hazard ratio [HR] 4.40; p = .002) and coronary artery disease (HR 2.70, p = .02), were independently associated with the occurrence of an AE during follow up. The small number of patients included prevented a separate analysis with regard to aneurysmal and occlusive aortic disease. CONCLUSION: This study suggests that even with a well trained surgical team, the laparoscopic approach increases the risk for AEs observed in the course of aortic surgery. ClinicalTrials.gov Identifier: NCT02325700.

[Efficacy and safety profile of cranberry in infants and children with recurrent urinary tract infection]. / Eficacia y perfil de seguridad del arándano americano en lactantes y niños con infección urinaria recurrente.

OBJECTIVE: Cranberry prophylaxis of recurrent urinary tract infection in infants has proven effective in the experimental model of the adult. There are few data on its efficacy, safety and recommended dose in the pediatric population. METHODS: A controlled, double-blind Phase III clinical trial was conducted on children older than 1 month of age to evaluate the efficacy and safety of cranberry in recurrent urinary tract infection. The assumption was of the non-inferiority of cranberry versus trimethoprim. Statistical analysis was performed using Kaplan Meier analysis. RESULTS: A total of 85 patients under 1 year of age and 107 over 1 year were recruited. Trimethoprim was prescribed to 75 patients and 117 received cranberry. The cumulative rate of urinary infection associated with cranberry prophylaxis in children under 1 year was 46% (95% CI; 23-70) in children and 17% (95% CI; 0-38) in girls, effectively at doses inferior to trimethoprim. In children over 1 year-old cranberry was not inferior to trimethoprim, with a cumulative rate of urine infection of 26% (95% CI; 12-41). The cranberry was well tolerated and with no new adverse effects. CONCLUSIONS: Our study confirms that cranberry is safe and effective in the prophylaxis of recurrent urinary tract infection in infants and children. With the doses used, their efficiency is not less than that observed for trimethoprim among those over 1 year-old. (Clinical Trials Registry ISRCTN16968287).

Open surgery for chronic limb ischemia: a review.

This review considers the role of the different revascularization strategies in patients with chronic limb ischemia (CLI) and reveals that clinical evidence guiding therapeutic decision-making in CLI is poor and only careful basic recommendations can be made. For diffuse aortoiliac disease with occlusion of the aorta, aortobifemoral bypass remains the best option if the patient is fit for open surgery. Unilateral iliac occlusion should be treated by primary stenting, but an iliofemoral bypass may be the best option when the disease extends down to the common and deep femoral arteries. For infrainguinal revascularisation, bypass using the saphenous vein remains the best option for patients with occlusion of the superficial femoral artery >25 cm and for patients with multiple occlusions of the infrapopliteal arteries. In the absence of leg veins, arm veins should be used. Prosthetic grafts are the last option. Endovascular techniques are recommended in patients with short arterial lesions and limited life expectancy <2 years. Finally some patients with CLI are best treated by primary amputation. In conclusion, this review demonstrates that neither an endo- first nor a bypass-first attitude is appropriate in patients with CLI and suggests that these patients should be cared for by specialists in a multidisciplinary center in order to preserve their life and limbs, to conduct clinical trials and to control costs.

The diabetic foot: a review.

Diabetic foot ulceration (DFU) is among the most frequent complications of diabetes. Neuropathy and ischaemia are the initiating factors and infection is mostly a consequence. We have shown in this review that any DFU should be considered to have vascular impairment. DFU will generally heal if the toe pressure is >55 mmHg and a transcutaneous oxygen pressure (TcPO2) <30 mmHg has been considered to predict that a diabetic ulcer may not heal. The decision to intervene is complex and made according to the symptoms and clinical findings. If both an endovascular and a bypass procedure are possible with an equal outcome to be expected, endovascular treatments should be preferred. Primary and secondary mid-term patency rates are better after bypass, but there is no difference in limb salvage. Bedridden patients with poor life expectancy and a non-revascularisable leg are indications for performing a major amputation. A deep infection is the immediate cause of amputation in 25% to 50% of diabetic patients. Patients with uncontrolled abscess, bone or joint involvement, gangrene, or necrotising fasciitis have a "foot-at risk" and need prompt surgical intervention with debridement and revascularisation. As demonstrated in this review, foot ulcer in diabetic is associated with high mortality and morbidity. Early referral, non-invasive vascular testing, imaging and intervention are crucial to improve DFU healing and to prevent amputation. Diabetics are eight to twenty-four times more likely than non-diabetics to have a lower limb amputation and it has been suggested that a large part of those amputations could be avoided by an early diagnosis and a multidisciplinary approach.

Urinary excretion of phenolic acids by infants and children: a randomised double-blind clinical assay.

OBJECTIVES: The present study, which is part of the ISRCTN16968287 clinical assay, is aimed at determining the effects of cranberry syrup or trimethoprim treatment for UTI. METHODS: This Phase III randomised clinical trial was conducted at the San Cecilio Clinical Hospital (Granada, Spain) with a study population of 192 patients, aged between 1 month and 13 years. Criteria for inclusion were a background of recurrent UTI, associated or otherwise with vesico-ureteral reflux of any degree, or renal pelvic dilatation associated with urinary infection. Each child was randomly given 0.2 mL/Kg/day of either cranberry syrup or trimethoprim (8 mg/mL). The primary and secondary objectives, respectively, were to determine the risk of UTI and the levels of phenolic acids in urine associated with each intervention. RESULTS: With respect to UTI, the cranberry treatment was non-inferior to trimethoprim. Increased urinary excretion of ferulic acid was associated with a greater risk of UTI developing in infants aged under 1 year (RR 1.06; CI 95% 1.024-1.1; P = 0.001). CONCLUSIONS: The results obtained show the excretion of ferulic acid is higher in infants aged under 1 year, giving rise to an increased risk of UTI, for both treatment options.

[Loss of quality of life in family caregivers of stroke patients: an entity to be considered]. / Deterioro de la calidad de vida en cuidadores familiares de pacientes con discapacidad por ictus: una entidad a considerar.

INTRODUCTION: Among stroke consequences highlights the negative impact on the informal carers' health related quality of life (HRQoL). OBJECTIVES: To identify HRQoL dimensions most greatly affected in stroke caregivers and establish relations with dependent variables of survivors and caregivers. METHODS: Transversal study of 215 informal caregivers of stroke survivors (1:3 man/woman, mean age 63.6 (±11.03) years). Main outcome measure was health perception assessed with the Short Fom 36 (SF-36). Clinical and demographic data of stroke patients were also registered. Statistical tests used were Chi-square, t-Student test and Spearman correlation coefficient. RESULTS: Vitality and general health were the most affected dimensions perceived by caregivers. In comparison with the Spanish general population, female caregivers aged 45-54 years presented a significant reduction in the SF-36 subscales of vitality (p=0.003), social function (p=0.01), emotional role (p=0.038) and mental health (p=0.002). Female caregivers aged 55-64 years also showed a significant reduction in social function (p=0.027) and emotional role (p=0.024). Male caregivers did not present significant lower HRQoL. CONCLUSIONS: Caregiving experience has a negative impact on HRQoL, specially middle-aged female caregivers. Some carer physical and psychological characteristics (depression, musculoskeletal pain, time spent on caring) and survivor disability shown to influence carers outcomes. Caregivers play an important role in the recovery of stroke patients, so that the identification of strategies which help them to cope with the stroke might avoid that the role of caring results in a loss of quality of life.

Overweight and obesity as risk factors for the asymptomatic carrier state of Neisseria meningitidis among a paediatric population.

We analysed the asymptomatic carrier state of Neisseria meningitidis in a sample of 339 children. We obtained data for the children's weight and height, in order to calculate the body mass index (BMI). The cutoff points defined by Cole were employed in determining the BMI, and the population was divided into three groups: normal, overweight and obese. Twenty carriers of N. meningitidis were identified. There was found to be a statistically significant trend to increased risk of being a carrier with increased BMI (z=2.03; P=0.04); after adjusting for age using the Mantel-Haenszel weighting method, this relationship was strengthened (z=2.38; P=0.01). Paediatric patients with increased BMI in the range of obesity present a three times greater risk of being carriers of N. meningitidis than non-obese patients, with a trend for this risk to increase with higher BMI.

[Short form 36 health questionnaire in hemiplegic patients 2 years after stroke]. / Cuestionario de salud Short Form 36 en pacientes hemipléjicos a los 2 años postictus.

INTRODUCTION: Many studies show that subjects with sequelae after stroke have a worse health perception in western societies. Due to the shortage of papers on the Spanish population in this regard, a study was carried out to assess health perception in hemiplegic patients 2 years after stroke in comparison with that of the general population and correlate health perception with demographic, clinical and functional variables. METHODS: Cross-sectional study of 212 community stroke survivors. The main variables collected were: health perception assessed with the Short Form 36 (SF-36), disability assessed with the motor Functional Independence Measure (FIM) and Geriatric Depression Scale (GDS). Statistical tests used: chi2, Student t test and Spearman correlation coefficient. RESULTS: In comparison with the Spanish general population, health perception in hemiplegic male stroke patients is diminished in all areas. In hemiplegic female patients, physical function is the only subscale significantly affected in all age groups. Variables related to worse health perception are: presence of depression, dependence and the belief of the need for kind of social support, A significant correlation was observed between SF-36 values and the motor FIM (r = 0.737 with physical function) and the GDS (r = -0.821 with mental health). CONCLUSIONS: Health perception in hemiplegic patients 2 years after stroke is diminished in comparison with that 348 of the general population. Factors which determine worst health perception are depression, motor dependence, need of caregiver assistance and need of social support.

[Paraganglioma of the vagus nerve]. / Paraganglioma del nervio vago.

Paragangliomas of the vagus nerve are uncommon vascular benign neoplasms of neuroectodermic origin. Initial clinical manifestation is usually as an asymptomatic cervical mass, although sometimes may cause lower cranial nerve palsies. These paragangliomas seldom associate to high levels of circulating catecholamines. Diagnosis is based on the clinics aided by imaging, where CT and MRI play an important role. Angiography is not only diagnostic, but it also allows preoperative embolization of the mass. Most accepted treatment is surgical removal, even though some paragangliomas are suitable for radiation therapy in very specific patients. In this paper we describe a new case of paraganglioma of the vagus nerve in a cervical location, with hypertensive episodes and high catecholamine-levels. The authors review the literature describing the clinical presentation, the diagnosis and the treatment of this rare lesion.

Trunk control test as a functional predictor in stroke patients.

The purpose of this study was to evaluate prospectively the Trunk Control Test (TCT) correlation at admission to rehabilitation with length of stay, functional independence measure (FIM), gait velocity, walking distance and balance measured at discharge in 28 hemiparetic patients. FIM and TCT were registered on admission. Outcome measures at discharge were: FIM, gait velocity, walking distance and balance assessed with the Berg Balance Scale and computerized posturography. TCT was significantly correlated with length of stay (r = -0.722), discharge FIM (r = 0.738), discharge motor FIM (r = 0.723), gait velocity (r = 0.654), walking distance (p = 0.003), centre of gravity symmetry r = 0.601) and Berg Balance Scale (r = 0.755). Initial TCT predicts the 52% of the variation in length of stay and 54% in the discharge FIM. The predictive value of a compound variable (TCT and admission FIM) reaches 60% of the variation in length of stay and 66% in the FIM at discharge.

A review of facial nerve outcome in 100 consecutive cases of acoustic tumor surgery.

OBJECTIVE: To determine the facial nerve outcomes at a tertiary neurotological referral center specializing in acoustic neuroma and skull base surgery. STUDY DESIGN: Retrospective review of 100 consecutive patients in whom acoustic neuromas were removed using all of the standard surgical approaches. METHODS: Functional facial nerve outcomes were independently assessed using the House-Brackmann facial nerve grading system. RESULTS: The tumors were categorized as small, medium, large, and giant. If one excludes the three patients with preoperative facial palsies, 100% of the small tumors, 98.6% of the medium tumors, 100% of the large tumors, and 71% of the giant tumors had facial nerve function grade I-II/VI after surgery. CONCLUSION: Facial nerve results from alternative nonsurgical treatments must be compared with facial nerve outcomes from experienced surgical centers. Based on the facial nerve outcomes from our 100 consecutive patients, microsurgical resection remains the preferred treatment modality for acoustic tumors.

Laser bronchoscopy with transglottic/supraglottic ventilation to relieve dysphonia and subglottic obstruction.

Dysphonia after endotracheal intubation usually indicates a glottic lesion but it can also herald an obstructing subglottic airway mass. Outpatient strobovideolaryngoscopy may be anatomically extended by transglottic videotracheobronchoscopy to achieve a thorough examination of the proximal bronchi, trachea, subglottis, glottis, and supraglottis in selected cases. Combining these techniques with lateral soft tissue x-ray studies of the neck in two patients with dysphonia and stridor, nearly identical postendotracheal intubation subglottic severely obstructing granulation "tumors" were diagnosed. Operative subglottic resection with a rigid ventilating laser bronchoscope combined with transglottic/supraglottic anesthetic ventilation techniques and contact-tip Nd-YAG laser phototherapy relieved the dysphonia and airway obstruction simultaneously. Normal vocal quality and full anatomical airway patency were achieved in both cases. Follow-up postoperative vocal rehabilitation and medical therapy sustained the surgical results.