Increased Risk of Local Recurrence in Cutaneous Squamous Cell Carcinoma Arising in Sun-Exposed Skin: A Retrospective Cohort Study.

BACKGROUND: The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing over the years. Risk factors for local recurrence and metastasis have been widely studied in highly sun-exposed areas of the body but less data exist about less sun-exposed ones. The main objective of this study is to compare the risk of local recurrence and metastases in patients with cSCC in highly sun-exposed areas compared to cSCC in less sun-exposed areas. MATERIAL AND METHODS: A retrospective observational study was carried out, including 558 patients with histopathologically confirmed cSCC at the Reina Sofía University Hospital (HURS), Córdoba, during the period from 1 January 2017 to 31 December 2020. Demographic, clinical and anatomopathological data were collected. RESULTS: Local recurrence occurs more often in highly sun-exposed areas (15.8%) compared to less sun-exposed ones (7.4%) (p < 0.05). However, no differences in the rate of metastases in both groups were found. The presence of affected surgical margins and tumor thickness were identified as independent risk factors for cSCC in low sun-exposure areas. CONCLUSIONS: cSCC located in anatomical areas of high sun exposure presented a greater risk of developing local recurrence in our population, which could suggest that these tumors have worse prognosis than those that lie in areas that do not receive chronic sun exposure.

Subspine femoroacetabular impingement: retrospective study of a series of patients treated by hip arthroscopic resection.

BACKGROUND: Femoroacetabular impingement syndrome (FAIS) is a common hip pathology that causes pain and functional limitation in young patients. subspine femoroacetabular impingement (SFAI) is an increasingly diagnosed extra-articular subtype that occurs from mechanical conflict of the anteroinferior iliac spine (AIIS) with the cervico-diaphyseal junction during hip flexion, which is poorly described in the literature. QUESTIONS/PURPOSES: We aimed to describe the clinical, functional, and radiological results of the arthroscopic treatment of a group of patients with SFAI treated in our Hip Unit. STUDY DESIGN: Case series. METHODS: We present a retrospective study of ten patients with SFAI treated between 2013 and 2020 with arthroscopic resection. Clinical results were assessed with scales such as visual analog scale (VAS); modified Harris Hip Score (mHHS), and Hip disability and Osteoarthritis Outcome Score (HOOS). Radiological results were assessed with radiological measurements, magnetic resonance imaging (MRI), and computed tomography (CT) reconstructions. RESULTS: Six patients had a Type III AIIS and four of them had Type II. Two patients had previously been surgically treated for FAIS. The range of motion improved in flexion from 107 ± 11 degrees before surgery to 127.5 ± 6 degrees (p = 0.005). MHHS improved from 48.1 (38-75.3) before surgery to 83.1 (57-91) (p = 0.007) and HOOS improved from 65.2 (58-75) to 89 (68.1-100) (p = 0.007). VAS improved from 7.3 (5-9) pre-surgical to 2.5 (0-8) post-surgical (p = 0.005). We did not have significant complications except for an asymptomatic case of heterotopic ossification (Brooker I). CONCLUSION: Arthroscopic decompression of AIIS in SFAI patients is a safe procedure that provides satisfactory short-term functional results, improving clinical symptoms, function, sports performance, and range of motion in our study.

Multiresistant Candida Endophthalmitis Treated with Intravitreal Caspofungin: A Case Report.

BACKGROUND: Candida endophthalmitis is a severe complication of candidemia. Currently, the recommended treatment of fungal endophthalmitis is a combination of intravitreal and systemic antifungal drugs, and in some cases vitrectomy is also required. Intravitreal therapies that are commonly used are amphotericin B and voriconazole, although recently the use of intravitreal caspofungin has been described in a few case reports. However, clinical experience with intravitreal caspofungin is still limited. CASE PRESENTATION: We report a case of bilateral candida tropicalis endophthalmitis, initially managed with repeated 100 µg/0.1 ml caspofungin intravitreal injections and posteriorly treated with pars plana vitrectomy in both eyes. CONCLUSIONS: Intravitreal caspofungin could be a safe intravitreal alternative to habitual antimycotic drugs in cases with resistant candida endophthalmitis.Abbreviations: Intensive Care Unit (ICU); Best-Corrected Visual Acuity (BCVA).

Prognostic Significance of Findings on CTPA Supporting an Alternative Diagnosis to PE Among Patients Hospitalized for an Exacerbation of COPD: Predefined Subanalysis of the SLICE Trial. / Significado pronóstico de los diagnósticos alternativos a la TEP hallados en la tomografía computarizada de tórax de pacientes ingresados por agudización de EPOC: subanálisis predefinido del ensayo SLICE.

BACKGROUND: Among patients hospitalized for an exacerbation of chronic obstructive pulmonary disease (COPD), the SLICE trial showed that the addition of an active diagnostic strategy for pulmonary embolism (PE) to usual care compared with usual care alone did not improve a composite set of health outcomes. The objective of this subanalysis was to determine the frequency and prognostic significance of findings on computed tomography pulmonary angiogram (CTPA) supporting an alternative diagnosis to PE. METHODS: We analyzed all patients randomized to the intervention in the SLICE trial who received a CTPA that did not show PE. We used multivariable logistic regression to assess the independent association between findings supporting an alternative diagnosis to PE and a composite of readmission for COPD or death within 90 days after randomization. RESULTS: Among the 746 patients who were randomized, this subanalysis included 175 patients in the intervention group who received a CTPA that did not show PE. Eighty-four (48.0%) patients had acute bronchial infection, 13 (7.4%) had lung cancer, 10 (5.7%) had congestive heart failure, 8 (4.6%), 18 (10.3%) had other diagnoses, and 42 (24.0%) had a normal CTPA. In multivariable analysis, findings supporting an alternative diagnosis to PE were not significantly associated with the primary outcome (odds ratio: 0.64; 95% confidence interval: 0.30-1.38; P=0.26). CONCLUSIONS: Among patients hospitalized for an exacerbation of COPD, CTPA identified an alternative diagnosis in 76% of the patients. However, specific management of these patients was not associated with improved outcomes within 90 days after randomization.

Connection between Mesenchymal Stem Cells Therapy and Osteoclasts in Osteoarthritis.

The use of mesenchymal stem cells constitutes a promising therapeutic approach, as it has shown beneficial effects in different pathologies. Numerous in vitro, pre-clinical, and, to a lesser extent, clinical trials have been published for osteoarthritis. Osteoarthritis is a type of arthritis that affects diarthritic joints in which the most common and studied effect is cartilage degradation. Nowadays, it is known that osteoarthritis is a disease with a very powerful inflammatory component that affects the subchondral bone and the rest of the tissues that make up the joint. This inflammatory component may induce the differentiation of osteoclasts, the bone-resorbing cells. Subchondral bone degradation has been suggested as a key process in the pathogenesis of osteoarthritis. However, very few published studies directly focus on the activity of mesenchymal stem cells on osteoclasts, contrary to what happens with other cell types of the joint, such as chondrocytes, synoviocytes, and osteoblasts. In this review, we try to gather the published bibliography in relation to the effects of mesenchymal stem cells on osteoclastogenesis. Although we find promising results, we point out the need for further studies that can support mesenchymal stem cells as a therapeutic tool for osteoclasts and their consequences on the osteoarthritic joint.

Perioperative interstitial high-dose-rate brachytherapy for keloids scar.

PURPOSE: To evaluate the results of keloids treated with perioperative interstitial high-dose-rate brachytherapy (HDR-BT). MATERIAL AND METHODS: A retrospective review of 61 keloids in 51 patients treated with perioperative interstitial HDR-BT was performed. Keloid lesions were treated with 12 Gy in 4 fractions within 48 hours. Time between surgery and brachytherapy was less than 90 minutes. Local failure was defined as recurrence of apparent keloid or symptoms in the same place. Median age of patients was 46 years (range, 20-89 years). Keloid scars were located on the chest (41%), ear lobe (21%), back (1.6%), extremities (11.5%), and mean keloid size was 6.3 cm. RESULTS: With a median follow-up of 47.95 months (range, 1-96 months), the recurrence rate was 4.9%, all located on the chest. The multivariate analysis showed no statistically significant relationship between location, scar size, and previously treated lesions with the recurrence rate. CONCLUSIONS: The treatment of keloid scars with perioperative interstitial high-dose-rate brachytherapy achieved excellent results, with a recurrence rate of only 4.9% and excellent cosmetic outcomes, suggesting that this technique might be one of the best options for treating keloids.

Clinical and Prognostic Impact of Low Diffusing Capacity for Carbon Monoxide Values in Patients With Global Initiative for Obstructive Lung Disease I COPD.

BACKGROUND: The Global Initiative for Obstructive Lung Disease (GOLD) does not promote diffusing capacity for carbon monoxide (Dlco) values in the evaluation of COPD. In GOLD spirometric stage I COPD patients, the clinical and prognostic impact of a low Dlco has not been explored. RESEARCH QUESTION: Could a Dlco threshold help define an increased risk of death and a different clinical presentation in these patients? STUDY DESIGN AND METHODS: GOLD stage I COPD patients (n = 360) were enrolled and followed over 109 ± 50 months. Age, sex, pack-years' history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, and history of exacerbations were recorded. A cutoff value for Dlco was identified for all-cause mortality and the clinical and physiological characteristics of patients above and below the threshold compared. Cox regression analysis explored the predictive power of that cutoff value for all-cause mortality. RESULTS: A Dlco cutoff value of <60% predicted was associated with all-cause mortality (Dlco ≥ 60%: 9% vs Dlco < 60%: 23%, P = .01). At a same FEV1% predicted and Charlson score, patients with Dlco < 60% had lower BMI, more dyspnea, lower inspiratory capacity (IC)/total lung capacity (TLC) ratio, lower 6-min walk distance (6MWD), and higher BODE. Cox multiple regression analysis confirmed that after adjusting for age, sex, pack-years history, smoking status, and BMI, a Dlco < 60% is associated with all-cause mortality (hazard ratio [HR], 95% CI = 3.37, 1.35-8.39; P = .009) INTERPRETATION: In GOLD I COPD patients, a Dlco < 60% predicted is associated with increased risk of death and worse clinical presentation. What the cause(s) of this association are and whether they can be treated need to be determined.

Ulcerative colitis induced by ixekizumab: a case report.

A possible case of ulcerative colitis (UC) developed during treatment with ixekizumab is reported. Ixekizumab is a human monoclonal antibody approved for chronic plaque psoriasis that works by blocking interleukin-17 (IL-17). Cytoquines, such as IL-17, may be involved in the pathophysiology of psoriasis and inflammatory bowel diseases. We describe the case of a 76-year-old woman who presented with an episode of acute self-limited colitis after receiving ten doses of ixekizumab. It was resolved after treatment withdrawal. A re-challenge was done after 3 months and symptoms returned. Colonoscopy results confirmed the diagnosis of UC. Symptoms remitted after drug discontinuation and treatment with corticosteroids. Four months after stopping ixekizumab, she remains asymptomatic and she is being treated with guselkumab with adequate response. The Naranjo algorithm revealed a probable causal relationship.This adverse event should be taken into account by physicians and pharmacists before prescribing or reviewing therapies in order to improve patients' safety.

Characteristics of Acute Nystagmus in the Pediatric Emergency Department.

OBJECTIVES: Acute nystagmus (AN) is an uncommon neurologic sign in children presenting to pediatric emergency departments. We described the epidemiology, clinical features, and underlying causes of AN in a large cohort of children, aiming at identifying features associated with higher risk of severe underlying urgent conditions (UCs). METHODS: Clinical records of all patients aged 0 to 18 years presenting for AN to the pediatric emergency departments of 9 Italian hospitals in an 8-year period were retrospectively reviewed. Clinical and demographic features and the underlying causes were analyzed. A logistic regression model was applied to detect predictive variables associated with a higher risk of UCs. RESULTS: A total of 206 patients with AN were included (male-to-female ratio: 1.01; mean age: 8 years 11 months). The most frequently associated symptoms were headache (43.2%) and vertigo (42.2%). Ataxia (17.5%) and strabismus (13.1%) were the most common neurologic signs. Migraine (25.7%) and vestibular disorders (14.1%) were the most common causes of AN. Idiopathic infantile nystagmus was the most common cause in infants <1 year of age. UCs accounted for 18.9% of all cases, mostly represented by brain tumors (8.3%). Accordant with the logistic model, cranial nerve deficits, ataxia, or strabismus were strongly associated with an underlying UC. Presence of vertigo or attribution of a nonurgent triage code was associated with a reduced risk of UCs. CONCLUSIONS: AN should be considered an alarming finding in children given the risk of severe UCs. Cranial nerve palsy, ataxia, and strabismus should be considered red flags during the assessment of a child with AN.

Study of Drilling Process by Cooling Compressed Air in Reinforced Polyether-Ether-Ketone.

This study is focused on the application of a cooling compressed air system in drilling processes; this environmentally friendly technique allows removing material at very low temperatures, approximately up to -22 °C in the cutting area. The main goals are to find the most improve cutting conditions with less energy consumption, for the drilling of reinforced polyether-ether-ketone with glass fiber at 30% (PEEK-GF30) with cooling compressed air by a Ranque-Hilsch vortex tube, and to find a balance between environmental conditions and adequate process performance. Drilling tests were carried out on plates of PEEK-GF30 to analyze the influence of cutting parameters and environmental temperature (-22, 0 and 22 °C) on variables such as thrust forces, energy and material removed rate by the use of statistical methods; analysis of variance, analysis of means, response surface, and desirability function were employed to identify the optimum region that provides the most improved values of the aforementioned variables. Drill bit diameter was also analyzed to determine the quality of drilled holes. During the drilling processes, force signals were detected by a piezoelectric dynamometer connected to multichannel amplifier and a pyrometer was used to control the temperature. The diameters of the drilled holes were measured by a coordinate measuring machine. Cooling compressed air can be considered an adequate technique to improve the results from an environmental and efficient perspective; in particular, the maximum desirability function was found at a spindle speed of 7000 rpm, a feedrate of 1 mm/rev and a temperature close to -22 °C.

Full-term pregnancy in breast cancer survivor with fertility preservation: A case report and review of literature.

A 43-year-old woman with an associated history of gynecological pathology and breast cancer with only one cryopreserved embryo wished to be a mother. Several factors that influenced the success of the pregnancy in this case were analyzed. Favorable factors included: triple positive breast cancer [positive hormone receptors and positive human epidermal growth factor receptor 2], which is more hormosensitive and chemosensitive; absence of metastasis; correct endometrium preparation; and the patient's optimistic attitude and strict health habits. In contrast, the factors against success were: breast cancer; adjuvant breast cancer therapy gonadotoxicity; the age of the patient (> 40-year-old); endometriosis; ovarian cyst; hydrosalpinx; submucosal fibroids and the respective associated surgery done for the above-mentioned pathology (all resolved prior to the embryo transfer); and a low quantity of ovules (low ovarian reserve) after ovarian stimulation. This is a very special clinical case of a patient with theoretically low pregnancy success probability due to the consecutive accumulation of gynecological and oncological pathologies, who nonetheless became pregnant and delivered a full-term infant and was able to provide adequate breastfeeding.

A Pharmacological Update of Ellagic Acid.

Ellagic acid is a common metabolite present in many medicinal plants and vegetables. It is present either in free form or as part of more complex molecules (ellagitannins), which can be metabolized to liberate ellagic acid and several of its metabolites, including urolithins. While ellagic acid's antioxidant properties are doubtless responsible for many of its pharmacological activities, other mechanisms have also been implicated in its various effects, including its ability to reduce the lipidemic profile and lipid metabolism, alter pro-inflammatory mediators (tumor necrosis factor-α, interleukin-1ß, interleukin-6), and decrease the activity of nuclear factor-κB while increasing nuclear factor erythroid 2-related factor 2 expression. These events play an important role in ellagic acid's anti-atherogenic, anti-inflammatory, and neuroprotective effects. Several of these activities, together with the effect of ellagic acid on insulin, glycogen, phosphatases, aldose reductase, sorbitol accumulation, advanced glycation end-product formation, and resistin secretion, may explain its effects on metabolic syndrome and diabetes. In addition, results from recent research have increased the interest in ellagic acid, both as a potential protective agent of the liver and skin and as a potential anticancer agent, due to the specific mechanisms affecting cell proliferation, apoptosis, DNA damage, and angiogenesis and its aforementioned anti-inflammatory properties. Taken together, these effects make ellagic acid a highly interesting compound that may contribute to different aspects of health; however, more studies are needed, especially on the compound's pharmacokinetic profile. In this review, we selected papers published from 2005 to the present.

Influence of Dimerization of Apocynin on Its Effects in Experimental Colitis.

Apocynin has been widely used as an inhibitor of the nicotinamide adenine dinucleotide phosphate oxidase (NADPH-oxidase) system and shows promise as an anti-inflammatory drug. Diapocynin, the dimeric product generated by the oxidation of apocynin in the presence of myeloperoxidase (MPO), is supposed to be its active form. In this study, diapocynin has been chemically synthesized and its activity on several inflammatory mediators in LPS-stimulated RAW 264.7 macrophages and its anti-inflammatory effect on ulcerative colitis induced by dextran sodium sulfate (DSS) in mice analyzed. We found that diapocynin showed higher inhibitory activity than apocynin. The dimer reduced ROS production, TNF-α, IL-6, and IL-1ß levels and inhibited iNOS and COX-2 expression as well as decreased NO and PGE2 production induced in LPS-stimulated RAW 264.7 cells. The anti-inflammatory molecular mechanism of diapocynin was associated with the suppression of NF-κB activation. However, these results were not paralleled by in vivo studies. Oral administration of apocynin and diapocynin (100 mg/kg) three times a week exhibited similar protections against experimental inflammatory bowel disease induced by DSS; therefore, apocynin should not be considered a prodrug. However, it should be taken into account that the dimer is more potent because its dose (0.3 mmol/kg) is half that of apocynin.

Lung cancer screening in patients with chronic obstructive pulmonary disease.

Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment.

Intestinal anti-inflammatory activity of ellagic acid in the acute and chronic dextrane sulfate sodium models of mice colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pomegranate (Punica granatum L.; Lythraceae) has traditionally been used for the treatment of various inflammatory diseases, including ulcerative colitis (UC). Because its fruits and extracts are rich in ellagitannins, which release ellagic acid when hydrolyzed, consumption of pomegranate products is currently being widely promoted for their potential health effects, including the prevention of inflammatory diseases and cancer. To evaluate the anti-inflammatory effects of ellagic acid on dextran sulfate sodium (DSS)-induced acute and chronic experimental colitis in two different strains of mice and to elucidate its possible mechanisms of action. MATERIALS AND METHODS: In the acute UC model, female Balb/C mice were treated with DSS (5%) for seven days while concomitantly receiving a dietary supplement of ellagic acid (2%). In the chronic UC model, female C57BL/6 mice received four week-long cycles of DSS (1% and 2%) interspersed with week-long recovery periods along with a diet supplemented with ellagic acid (0.5%). RESULTS: In acute model of UC, ellagic acid ameliorated disease severity slightly as observed both macroscopically and through the profile of inflammatory mediators (IL-6, TNF-α, and IFN-γ). In the chronic UC model, ellagic acid significantly inhibited the progression of the disease, reducing intestinal inflammation and decreasing histological scores. Moreover, mediators such as COX-2 and iNOS were downregulated and the signaling pathways p38 MAPK, NF-κB, and STAT3 were blocked. CONCLUSIONS: Our study reinforces the hypothetical use of ellagic acid as an anti-inflammatory complement to conventional UC treatment in chronic UC patients and could be considered in the dietary prevention of intestinal inflammation and related cancer development.

Protective effect of apocynin in a mouse model of chemically-induced colitis.

Apocynin, a constituent of Picrorhiza kurroa, successfully inhibits NADPH oxidase and shows promise as an anti-inflammatory drug. Now, we report anti-inflammatory effects of apocynin in an experimental colitis model induced by dextran sulfate sodium as well as the effects on the mediators involved in this process. Apocynin reduced the colitis induced in mice by administration of 5 % dextran sulfate sodium during 7 days. Mice were fed a control diet or a diet supplemented with 2 % of apocynin or 2 % of rutin. Sulfasalazine (50 mg/kg, p. o.) was used as a positive control. Treatment with apocynin and rutin ameliorated the course of colonic inflammation with results similar to those of the reference drug, as could be seen by reductions in the disease activity index scores and colon length. NO and PGE2 production as well as the iNOS and COX-2 expression were reduced by apocynin and rutin. Moreover, the activation of NF-κB p65 as well as STAT3 in dextran sulfate sodium-treated colon tissues was significantly reduced by apocynin. These results are promising for further experimental studies on treating gastrointestinal diseases and on the potential protective effects of apocynin.