Intralesional photodynamic therapy induces apoptosis in basal cell carcinoma and Bowen's disease through caspase 3 and granzyme B.

BACKGROUND: Photodynamic therapy (PDT) is used to treat cutaneous cancers. It may induce cell death through direct and indirect means, including apoptosis, inflammation and certain immune mechanisms, with the depth of penetration as a potential modifying factor. OBJECTIVES: To examine the pathways of apoptosis in the intralesional PDT of basal cell carcinoma (BCC) and intraepidermal squamous cell carcinoma (Bowen's disease). METHODS: Sixteen patients with superficial or nodular BCC and Bowen's disease were treated with intralesional aminolevulinic acid-PDT. Biopsies were taken at baseline and 24 h post-PDT, and sections were examined by immunohistochemistry for the expression of markers of apoptosis, such as caspase 3, involved in the intrinsic apoptotic pathway, granzyme B, a caspase-independent apoptotic mediator, and the proapoptotic markers BAX and BAK. RESULTS: Apoptotic cells stained with TUNEL showed statistically significant staining at 24 h post PDT (p < 0.01 in both BCC and Bowen's lesions). Caspase 3 (p < 0.01 in BCC and p < 0.05 in Bowen's) and granzyme B (p < 0.01 in BCC and p < 0.01 in Bowen's) were significantly increased at 24 h post-PDT. BAX expression was apparently increased compared to baseline in Bowen's lesions at 24 h post-PDT, whereas Bak was upregulated both in BCC and Bowen's disease at baseline and at 24 h post-PDT. CONCLUSION: Intralesional PDT induces apoptosis in BCC and Bowen's disease via common and alternative apoptotic pathways involving granzyme B. Proapoptotic factors Bak in both BCC and Bowen and Bax in Bowen's disease appear to increase by intralesional PDT at 24 h.

Surgery for colorectal cancer in elderly patients: is there such a thing as being too old?

INTRODUCTION: The overall increase in life expectancy causes a rapid increase in number of elderly patients needing colorectal surgery. It remains unclear if there is a significant risk factor in patients over 80 years of age for postoperative morbidity and mortality. For this reason we investigated the perioperative, outcome and long-term survival after surgery for colorectal cancer in our hospital. MATERIALS AND METHODS: We retrospectively analysed a database containing information about patients who underwent surgery for colorectal cancer from January 2010 to December 2015 at the St. Bernhard Hospital in Kamp-Lintfort, Germany. The last follow-up date was 31th of December 2017. RESULTS: A total of 232 patients were enrolled and analysed in this study. All patients were separated in tow groups depending in age. The first group was ≥80 years old (n=49). The second group was <80 years old (n=183). High ASA-Scores (≥3) were detectable more often in elderly patients (p<0,05). Elderly and young patients had a similar risk for postoperative anastomosic leakages (p=0,047). Likewise there were no significant differences regarding the Dindo-Clavien-Classification (p=0,13). The mortality within the first 30 days after surgery was significant elevated for elderly patients compared to younger patients (p=0,04). Also the overall 1-year survival was 90% for the younger and 73,5% for the older study group (p<0,05) Conclusion. Both the short-term outcome and long-term survival rate after colorectal surgery for cancer are worse for patients older than 80 years of age. After interpretation of all data it remains unclear if the age itself is still the biggest risk factor. When old patients have a good ASA-Score and no severe comorbidities, colorectal surgery remains safe even for patients older than 80 years.

Right ventricular assessment of the adolescent footballer's heart.

INTRODUCTION: Athletic training can result in electrical and structural changes of the right ventricle that may mimic phenotypical features of arrhythmogenic right ventricular cardiomyopathy (ARVC), such as T-wave inversion and right heart dilatation. An erroneous interpretation may have consequences ranging from false reassurance in an athlete vulnerable to cardiac arrhythmias, to unnecessary sports restriction in a healthy individual. The primary aim of this study was to define normal RV dimension reference ranges for academy adolescent footballers of different ethnicities. Secondary aims include analysis of potential overlap between this adolescent group with ARVC criteria and comparison with normal adult ranges. RESULTS: Electrocardiographic (ECG) and echocardiographic data of 1087 academy male footballers aged between 13 and 18 years old (mean age 16.0 ± 0.5 years), attending mandatory cardiac screening were analysed. Ethnicity was categorised as white (n = 826), black (African/Caribbean; n = 166) and mixed-race (one parent white and one parent black; n = 95). Arrhythmogenic right ventricular cardiomyopathy major criteria for T-wave inversion was seen in 3.3% of the cohort. This was more prevalent in black footballers (12%) when compared to mixed race footballers (6.3%) or white footballers (1%), P < 0.05. Up to 59% of the cohort exceeded adult reference ranges for some of the right ventricular parameters, although values were similar to those seen in adult footballers. There were no differences in right ventricular dimensions between ethnicities. In particular, the right ventricular outflow tract diameter would fulfil major criteria for ARVC dimension in 12% of footballers. Overall, 0.2% of the cohort would fulfil diagnosis for 'definite' arrhythmogenic right ventricular cardiomyopathy and 2.2% would fulfil diagnosis for 'borderline' arrhythmogenic right ventricular cardiomyopathy for RV dimensions and ECG changes. This was seen more frequently in black footballers (9.9%) than mixed race footballers (3.9%) or white footballer (0.6%), P < 0.05. Among athletes meeting definite or borderline arrhythmogenic right ventricular cardiomyopathy criteria, no cardiomyopathy was identified after comprehensive clinical assessment, including with cardiac magnetic resonance imaging, exercise testing, ambulatory electrocardiograms and familial evaluation. CONCLUSION: Right heart sizes in excess of accepted adult ranges occurred in as many as one in two adolescent footballers. Structural adaptations in conjunction with anterior T-wave inversion may raise concern for ARVC, highlighting the need for evaluation in expert settings.

Prevalence and Clinical Significance of Electrocardiographic Complete Right Bundle Branch Block in Young Individuals.

BACKGROUND AND AIMS: There is limited information on the clinical significance of complete right bundle branch block (CRBBB) in young individuals. The aim of this study was to determine the prevalence and significance of CRBBB in a large cohort of young individuals aged 14-35 years old. METHODS: From 2008 to 2018, 104,369 consecutive individuals underwent a cardiovascular assessment with a health questionnaire, electrocardiogram, clinical consultation, and selective echocardiography. Follow-up was obtained via direct telephone consultations. Mean follow-up was 7.3 ± 2.7 years. RESULTS: CRBBB was identified in 154 (0.1%) individuals and was more prevalent in males compared with females (0.20% vs. 0.06%; p<0.05) and in athletes compared with non-athletes (0.25% vs. 0.14%; p<0.05). CRBBB-related cardiac conditions were identified in 7 (5%) individuals (4 with atrial septal defect, 1 with Brugada syndrome, 1 with progressive cardiac conduction disease and 1 with atrial fibrillation). Pathology was more frequently identified in individuals with non-isolated CRBBB compared with individuals with isolated CRBBB (14% vs 1%; p < 0.05) and in individuals with a QRS duration of ≥130 milliseconds (ms) compared with individuals with a QRS of <130ms (10% vs 1%; p<0.05). CONCLUSION: The prevalence of CRBBB in young individuals was 0.1% and was more prevalent in males and athletes. CRBBB-related conditions were identified in 5% of individuals and were more common in individuals with non-isolated CRBBB and more pronounced intraventricular conduction delay (QRS duration of ≥130ms). Secondary evaluation should be considered for young individuals with CRBBB with symptoms, concerning family history, additional electrocardiographic anomalies or significant QRS prolongation (≥130ms).

There is limited information on the clinical significance of complete right bundle branch block (CRBBB) in young people (aged 14 to 35 years old). CRBBB is a rare finding in young individuals and is more common in male and athletic individuals. CRBBB related-conditions are found in 5% of young individuals with this electrocardiogram finding and are more common in those with additional heart symptoms, family history of premature heart disease, other abnormal electrocardiographic (ECG) findings and more pronounced forms of CRBBB (≥ 130 milliseconds). Further investigation, including at least an ultrasound of the heart (echocardiogram), is recommended for all young individuals with CRBBB with concerning symptoms, family history of heart disease, additional ECG anomalies or more pronounced CRBBB (≥130milliseconds).

The potential therapeutic effect of metformin in type 2 diabetic patients with severe COVID-19.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is regarded as a chief risk factor for(coronavirus disease 2019 (COVID-19) owing to dysregulation of the expression of angiotensin-converting enzyme 2 (ACE2) and chronic low-grade inflammatory disorders. Metformin, an insulin-sensitizing agent for managing T2DM, has pleiotropic anti-inflammatory and oxidant potentials, which may lessen the risk of diabetic complications. So, we aimed to reveal the potential role of metformin monotherapy in treating T2DM patients with COVID-19. PATIENTS AND METHODS: In this prospective cohort study, 60 hospitalized T2DM patients with COVID-19 on metformin plus standard anti-COVID-19 treatments compared to 40 hospitalized T2DM patients with COVID-19 on other diabetic pharmacotherapy like insulin and sulfonylurea, were recruited. Inflammatory and oxidative stress biomarkers and radiological and clinical outcomes were assessed at admission time and at the time of discharge. RESULTS: The results of this study illustrated that metformin treatment in T2DM patients with COVID-19 was more effective in reducing inflammatory and oxidative stress biomarkers with significant amelioration of radiological scores and clinical outcomes compared to T2DM patients with COVID-19 on another diabetic pharmacotherapy. CONCLUSIONS: Our findings highlighted that metformin efficiently managed T2DM patients with COVID-19 by reducing inflammatory and oxidative stress with mitigating effects on the radiological scores and clinical outcomes.

Results of a nationally implemented cardiac screening programme in elite cricket players in England and Wales.

OBJECTIVES: We assessed the diagnostic yield and costs of an electrocardiogram-based national screening programme in elite cricket players and the incremental value of transthoracic echocardiography and periodic evaluation. DESIGN: Cross-sectional study. METHODS: Between 2008 and 2019, 1208 cricketers underwent screening with a health questionnaire, 12-lead electrocardiogram and cardiology consultation. Athletes with concerning findings underwent on-site transthoracic echocardiography and further investigations as necessary. In addition, despite a normal health questionnaire and electrocardiogram, 342 (28.3%) athletes had a transthoracic echocardiogram and 493 (40.8%) underwent repeat evaluations. RESULTS: After initial evaluation, 47 (3.9%) athletes underwent on-site transthoracic echocardiography of whom 35 (2.8%) were referred for further evaluation. Four athletes (0.3%) were diagnosed with major cardiac conditions; hypertrophic cardiomyopathy (n = 1), arrhythmogenic cardiomyopathy (n = 1) and Wolff-Parkinson-White pattern (n = 2). Two athletes were identified with minor valvular abnormalities. Repeat evaluation of 493 athletes identified hypertrophic cardiomyopathy in a 22-year-old athlete, two years after his initial normal screening. During a follow-up of 5.8 ±â€¯2.9 years no additional diagnoses or adverse cardiac events were reported. The cost of the electrocardiogram-based programme was £127,844, translating to £106 per athlete and £25,569 per major cardiac condition identified.Routine transthoracic echocardiography in 342 athletes identified two athletes with major cardiac conditions (bicuspid aortic valve with severe aortopathy and aortic regurgitation and an atrial septal defect associated with right ventricular volume overload) and 10 athletes with minor abnormalities. CONCLUSIONS: An electrocardiogram-based national screening programme identified a major cardiac condition in 0.3% of athletes. Routine transthoracic echocardiography and periodic evaluation increased the diagnostic yield to 0.6%, at an incremental cost.

Ethnic differences in physiological cardiac adaptation to intense physical exercise in highly trained female athletes.

BACKGROUND: Ethnicity is an important determinant of cardiovascular adaptation in athletes. Studies in black male athletes reveal a higher prevalence of electric repolarization and left ventricular hypertrophy than observed in white males; these frequently overlap with those observed in cardiomyopathy and have important implications in the preparticipation cardiac screening era. There are no reports on cardiac adaptation in highly trained black females, who comprise an increasing population of elite competitors. METHODS AND RESULTS: Between 2004 and 2009, 240 nationally ranked black female athletes (mean age 21+/-4.6 years old) underwent 12-lead ECG and 2-dimensional echocardiography. The results were compared with 200 white female athletes of similar age and size participating in similar sports. Black athletes demonstrated greater left ventricular wall thickness (9.2+/-1.2 versus 8.6+/-1.2 mm, P<0.001) and left ventricular mass (187.2+/-42 versus 172.3+/-42 g, P=0.008) than white athletes. Eight black athletes (3%) exhibited a left ventricular wall thickness >11 mm (12 to 13 mm) compared with none of the white athletes. All athletes revealed normal indices of systolic and diastolic function. Black athletes exhibited a higher prevalence of T-wave inversions (14% versus 2%, P<0.001) and ST-segment elevation (11% versus 1%, P<0.001) than white athletes. Deep T-wave inversions (-0.2 mV) were observed only in black athletes and were confined to the anterior leads (V(1) through V(3)). CONCLUSIONS: Systematic physical exercise in black female athletes is associated with greater left ventricular hypertrophy and higher prevalence of repolarization changes than in white female athletes of similar age and size participating in identical sporting disciplines. However, a maximal left ventricular wall thickness >13 mm or deep T-wave inversions in the inferior and lateral leads are rare and warrant further investigation.

The impact of bone mineral density on the degree of curvature of the lumbar spine.

OBJECTIVE: The prevailing perception is that one of the causes of postural deformities is osteoporosis. Nonetheless, studies of the correlation between bone mineral density (BMD) and spinal curvatures have produced contradictory results. This study was undertaken in order to determine whether (BMD) is associated with the curvature of the lumbar spine. METHODS: 105 postmenopausal women, aged 45-76 years (average= 57.3 years), were examined. All the participants underwent DXA scanning and spinal radiography using the same equipment and techniques. Lumbar curvatures were measured using the Cobb method. Subjects were divided according to their T-score into osteoporosis patients (n=54) and controls (n=51). Statistical analysis was performed using one way ANOVA, Mann-Whitney as well as Pearson and Spearman rank correlations. RESULTS: There were no statistically significant correlations between BMD and lumbar curvature angles either in the total sample or in either group individually. Furthermore, these angles were not significantly different between patients with osteoporosis and controls. CONCLUSIONS: The reduction in BMD and the alteration of the lumbar curvature that are observed in elderly individuals are concurrent but not related phenomena. The findings of this study contradict the claim that reduced bone mineral density is the cause of postural deformities.

Clinical significance of hepatitis B surface antigen in cord blood of hepatitis B e-antigen-negative chronic hepatitis B virus-infected mothers.

Vertical transmission of hepatitis B virus (HBV) infection during the perinatal period is the major cause of HBV transmission. The aim of our study was to evaluate the serological and virological profiles of HBV infection in cord blood samples obtained from HBeAg-negative chronic HBV-infected women, at delivery, and to investigate their relationship with the clinical outcome (possible transmission of HBV) in neonates receiving the currently approved passive-active immunoprophylaxis schedule. Sixteen women (32%) exhibited HBsAg positivity in the cord blood but HBV-DNA has not been detected in any of the 50 cord blood samples evaluated. We conclude that HBsAg can be transferred through the placental barrier, as with other proteins, in about one third of HBeAg-negative chronic HBV-infected pregnant women, irrespective of the maternal viral load, the mode of delivery or the placenta HBV pathology. The clinical impact of this phenomenon on the intrauterine-transplacental or perinatal transmission of HBV infection and/or passive-active immunoprophylaxis failure does not seem to be important.

Electrocardiographic screening in athletes: the time is now for universal screening.

Regular physical exercise reduces cardiovascular morbidity and mortality. A small proportion of athletes, however, are at increased risk of exercise-related sudden cardiac death (SCD) as a result of quiescent cardiac anomalies. The preventable nature of such deaths has prompted the medical and sporting governing bodies to recommend preparticipation cardiovascular screening (PPS) in young athletes (< or =35 years) to permit the identification of potentially fatal disorders. Although evidence from the Italian experience suggests that electrocardiographic screening of young athletes has led to a significant reduction in SCD from cardiomyopathies, considerable controversy relating to the efficacy, cost-effectiveness and the impact of false-positive results of PPS still exists. This review presents an appraisal of all the available scientific evidence, attempting to resolve the concerns of the antagonists and examine how PPS compares with the World Health Organization screening criteria, providing compelling justifications for the implementation of universal PPS in young, competitive athletes.

A Case Report of Aggressive Chronic Rhinosinusitis with Nasal Polyps Mimicking Sinonasal Malignancy.

INTRODUCTION: Cases of extensive nasal polyps rarely occur and may mimic more aggressive lesions of the nose and paranasal sinuses. A case of extensive nasal polyposis with unusually aggressive behavior and its management is presented. PRESENTATION OF CASE: A 27-year-old male patient visited the emergency department of a tertiary center, complaining of recurrent episodes of epistaxis. The patient presented with a large polypoid lesion protruding from the right nostril and producing asymmetry of the face. Diagnostic imaging illustrated a lesion of the right maxillary sinus producing excessive bone remodeling and extension into neighboring structures in every direction. Fine limits were noted, however, with no invasive characteristics. Biopsy under local anesthesia was performed, showing findings consistent with nonspecific inflammation. Open surgery through a lateral rhinotomy under general anesthesia was performed, and the mass was readily mobilized and removed. No macroscopic invasion of neighboring structures was noted. Permanent histology confirmed the diagnosis of nasal polyposis. Postoperative follow-up has shown no evidence of recurrence after 12 months. CONCLUSION: Nasal polyps do not typically expand in an aggressive manner, producing bone resorption or extending into neighboring structures. However, nasal polyposis should be included in the differential diagnosis of nasal tumors with such behavior.

Left Ventricular Function and Cardiac Biomarker Release-The Influence of Exercise Intensity, Duration and Mode: A Systematic Review and Meta-Analysis.

OBJECTIVE: We performed a systematic review, meta-analysis and meta-regression of exercise studies that sought to determine the relationship between cardiac troponin (cTn) and left ventricular (LV) function. The second objective was to determine how study-level and exercise factors influenced the variation in the body of literature. DATA SOURCES: A systematic search of Pubmed Central, Science Direct, SPORTDISCUS and MEDLINE databases. ELIGIBILITY CRITERIA: Original research articles published between 1997 and 2018 involving > 30 mins of continuous exercise, measuring cardiac troponin event rates and either LV ejection fraction (LVEF) or the ratio of the peak early (E) to peak late (A) filling velocity (E/A ratio). DESIGN: Random-effects meta-analyses and meta-regressions with four a priori determined covariates (age, exercise heart rate [HR], duration, mass). REGISTRATION: The systematic search strategy was registered on the PROSPERO database (CRD42018102176). RESULTS: Pooled cTn event rates were evident in 45.6% of participants (95% confidence interval (CI) 33.6-58.2); however, the overall effect was non-significant (P > 0.05). There were significant (P < 0.05) reductions in E/A ratio of - 0.38 (SMD = - 1.2, 95% CI - 1.4 to - 1.0), and LVEF of - 2.02% (SMD = - 0.38, 95% CI - 0.7 to - 0.1) pre- to post-exercise. Increased exercise HR was a significant predictor of troponin release and E/A ratio. Participant age was negatively associated with cTn release. There was a significant negative association between E/A ratio with increased rates of cTn release (P < 0.05). CONCLUSIONS: High levels of statistical heterogeneity and methodological variability exist in the majority of EICF studies. Our findings show that exercise intensity and age are the most powerful determinants of cTn release. Diastolic function is influenced by exercise HR and cTn release, which implies that exercise bouts at high intensities are enough to elicit cTn release and reduce LV diastolic function. Future EICF studies should (1) utilise specific echocardiographic techniques such as myocardial speckle tracking, (2) ensure participants are euhydrated during post-exercise measurements, and (3) repeat measures in the hours following exercise to assess symptom progression or recovery. It is also recommended to further explore the relationship between aging, training history, and exercise intensity on cTn release and functional changes.

Transforming a conventional theatre into a gynaecological endoscopy unit.

OBJECTIVE: Most minimally invasive procedures are now performed in operating rooms that were originally designed for traditional open surgery. We designed an endoscopic theatre based on our experience with special features specific for gynaecological endoscopy. METHOD: We designed a detailed plan with an architect's aid of a gynaecological unit (based on a Greek presidential decree published in 1991). The space utilized was that of a conventional theatre. RESULTS: With the architectural plan we anticipated every area needed in a gynaecological endoscopic theatre. A twin theatre was considered appropriate in order for the surgical team to operate alternatively in one theatre while the other is being cleaned and prepared for use. CONCLUSION: The design of a unit dedicated to gynaecologic laparoscopy is a multidisciplinary task where the endoscopic surgeon undertakes an active and prominent role. It is a project with great benefits and rewards for all parties involved. We present our design for evaluation.

Automated 3-D Detection of Dendritic Spines from In Vivo Two-Photon Image Stacks.

Despite the significant advances in the development of automated image analysis algorithms for the detection and extraction of neuronal structures, current software tools still have numerous limitations when it comes to the detection and analysis of dendritic spines. The problem is especially challenging in in vivo imaging, where the difficulty of extracting morphometric properties of spines is compounded by lower image resolution and contrast levels native to two-photon laser microscopy. To address this challenge, we introduce a new computational framework for the automated detection and quantitative analysis of dendritic spines in vivo multi-photon imaging. This framework includes: (i) a novel preprocessing algorithm enhancing spines in a way that they are included in the binarized volume produced during the segmentation of foreground from background; (ii) the mathematical foundation of this algorithm, and (iii) an algorithm for the detection of spine locations in reference to centerline trace and separating them from the branches to whom spines are attached to. This framework enables the computation of a wide range of geometric features such as spine length, spatial distribution and spine volume in a high-throughput fashion. We illustrate our approach for the automated extraction of dendritic spine features in time-series multi-photon images of layer 5 cortical excitatory neurons from the mouse visual cortex.

Neuroprotection and neurogenesis: modulation of cornus ammonis 1 neuronal survival after transient forebrain ischemia by prior fimbria-fornix deafferentation.

Severe transient forebrain ischemia causes selective neuronal death in the hippocampal cornus ammonis 1 region. We tested the hypothesis that fimbria-fornix deafferentation can provide long-term protection to cornus ammonis 1 neurons and modulate neurogenesis following ischemia. Fimbria-fornix lesion or sham-fimbria-fornix lesion was performed on Wistar rats 13 days prior to 10 min forebrain ischemia or sham ischemia. Temperature was regulated and rats survived for 7, 14 or 28 days. Immunofluorescent bromodeoxyuridine and neuron specific nuclear protein staining and immunochemistry terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining were performed. At 7 days after ischemia, 73%+/-14% of cornus ammonis 1 neurons were damaged, while deafferentation reduced the injury to 36%+/-17% of cornus ammonis 1 neurons. This protection persisted for at least 28 days. Ischemia significantly increased the number of bromodeoxyuridine-positive cells (85-90 cells/section in stroke group vs. 6 to 11 cells/section in normal or sham stroke group), with very few terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-stained cells adjacent to the hippocampal cornus ammonis 1. Fimbria-fornix lesioning followed by ischemia increased the percentage of new neurons 13-fold over ischemia alone and 6.5-fold over sham lesion plus ischemia. The results indicate that fimbria-fornix deafferentation provides long-term neuroprotection in cornus ammonis 1 following forebrain ischemia and promotes neurogenesis after ischemic insults.