Comparative proteomics of a versatile, marine, iron-oxidizing chemolithoautotroph.

This study conducted a comparative proteomic analysis to identify potential genetic markers for the biological function of chemolithoautotrophic iron oxidation in the marine bacterium Ghiorsea bivora. To date, this is the only characterized species in the class Zetaproteobacteria that is not an obligate iron-oxidizer, providing a unique opportunity to investigate differential protein expression to identify key genes involved in iron-oxidation at circumneutral pH. Over 1000 proteins were identified under both iron- and hydrogen-oxidizing conditions, with differentially expressed proteins found in both treatments. Notably, a gene cluster upregulated during iron oxidation was identified. This cluster contains genes encoding for cytochromes that share sequence similarity with the known iron-oxidase, Cyc2. Interestingly, these cytochromes, conserved in both Bacteria and Archaea, do not exhibit the typical ß-barrel structure of Cyc2. This cluster potentially encodes a biological nanowire-like transmembrane complex containing multiple redox proteins spanning the inner membrane, periplasm, outer membrane, and extracellular space. The upregulation of key genes associated with this complex during iron-oxidizing conditions was confirmed by quantitative reverse transcription-PCR. These findings were further supported by electromicrobiological methods, which demonstrated negative current production by G. bivora in a three-electrode system poised at a cathodic potential. This research provides significant insights into the biological function of chemolithoautotrophic iron oxidation.

First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743.

BACKGROUND: In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up. PATIENTS AND METHODS: Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of ≤1 were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or six cycles of platinum plus pemetrexed chemotherapy. This report includes updated efficacy and safety outcomes, exploratory biomarker analyses including four-gene inflammatory expression signature score, and a post hoc efficacy analysis in patients who discontinued treatment due to treatment-related adverse events (TRAEs). RESULTS: With a median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong OS versus chemotherapy. Median OS was 18.1 versus 14.1 months [hazard ratio (95% confidence interval), 0.73 (0.61-0.87)], and 3-year OS rates were 23% versus 15%, respectively. Three-year progression-free survival rates were 14% versus 1%, and objective response rates were 40% versus 44%. At 3 years, 28% versus 0% of responders had an ongoing response. Improved survival benefit with nivolumab plus ipilimumab versus chemotherapy was observed across subgroups, including histology. A high score of the four-gene inflammatory signature appeared to correlate with improved survival benefit with nivolumab plus ipilimumab. No new safety signals were observed with nivolumab plus ipilimumab, despite patients being off therapy for 1 year. In patients who discontinued nivolumab plus ipilimumab due to TRAEs, median OS was 25.4 months, and 34% of responders maintained their responses for ≥3 years after discontinuation. CONCLUSIONS: With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology.

A Low Body Fat Mass Ratio Predicts Poor Prognosis in Patients with Advanced Non-Small Cell Lung Cancer.

PURPOSE: The aim of this study was to investigate the effect of the body fat mass ratio on survival and prognosis in advanced non-small-cell lung cancer patients. METHODS: The study includes 200 patients who were diagnosed with advanced non-small-cell lung cancer between 2014 and 2018 and whose body fat mass percentage and body mass index (BMI) were determined using the Tanita Body Composition Analyzer during admission. RESULTS: All patients had advanced incurable non-small-cell lung cancer (30% had locally advanced disease, 70% were stage IV). In the univariate and multivariate analyses, age, gender, histopathological type, smoking history, comorbidities, weight loss in the last six months and body mass index had no statistically significant effect on survival (p > 0.05). However, the performance status (p = 0.008), metastatic status (p = 0.003) and body fat mass ratio (p = 0.01) were found to have a significant effect on overall survival (OS): the median OS was 16.4 mo, in patients with the BFM ratio ≤ 22% and 29.2 mo, in those with > 22% (p = 0.01). CONCLUSION: In this study, it was found that the body fat mass ratio was an important prognostic factor in patients with advanced non-small-cell lung cancer.

A rare tumor case in an adult patient with neurofibromatosis: Lumbar ependymoma.

In patients with type 1 neurofibromatosis (NF1), there is an increased susceptibility to tumor development in the central nervous system due to the loss of neurofibromin, an inactivator of the protooncogene Ras. NF1 has a broad clinical spectrum,which includes spinal tumors. Although the most common intramedullary tumor of the spinal cord in adults is ependymoma, few patients with NF1 accompanied by spinal ependymoma have been reported to date, and the localization of the tumors is cervical and thoracic in these cases. In this study, we report the case of a patient with NF1 presenting to our clinic with low back pain and gait disturbance. The patient had an intradural extramedullary ependymoma at the L2-3 vertebra level. This report is the first case of NF1 with spinal ependymoma localized in the lumbar region.

Efficacy and tolerability of current treatments for hormone-refractory prostate cancer patients with visceral metastases.

Aim: To assess the efficacy and tolerability of the first-line treatment options for hormone-refractory prostate cancer patients with visceral metastases. Materials & methods: The records of 191 patients diagnosed with hormone-refractory prostate cancer with visceral metastases were analyzed retrospectively. Results: Docetaxel was administered to 61.2% (n = 117), abiraterone to 14.2% (n = 27) and enzalutamide to 9.4% (n = 18) as the first-line treatment. The median survival of the patients receiving docetaxel, abiraterone and enzalutamide as the first-line treatment during the hormone-refractory period was 15 (95% Cl: 12.9-17) months, 6 (95% Cl: 1.8-10.1) months and 11 (95% Cl: 0.9-23.1) months (p = 0.038), respectively. Conclusion: The present study established a statistically significant difference in favor of docetaxel in terms of overall survival and progression-free survival.

Lay abstract The optimal therapeutic option for castration-resistant prostate cancer (CRPC) patients with visceral metastases is unknown. We assessed the efficacy and tolerability of the first-line treatment options for CRPC patients with visceral metastasis. One hundred ninety-one patients diagnosed with CRPC with visceral metastases were included in the study. The present study established a statistically significant difference in favor of docetaxel in terms of overall survival and progression-free survival between first-line docetaxel, abiraterone and enzalutamide treatments in CRPC patients with visceral metastases. For patients who cannot undergo chemotherapy, enzalutamide, among novel androgen pathway inhibitors, may be the most appropriate option, given its numerical, although statistically insignificant, difference in overall survival and its fewer side effects compared with abiraterone.

Potential role of the geriatric nutritional risk index as a novel risk factor for the development of non-valvular atrial fibrillation in patients with heart failure.

PURPOSE: The geriatric nutritional risk index (GNRI) is a simple and objective nutritional assessment tool for elderly patients. Lower GNRI values are associated with a worse prognosis in heart failure with reduced ejection fraction (HFrEF). Our aim is to investigate the relationship between malnutrition and follow-up cardiovascular (CV) events in HFrEF. METHODS: A retrospective study was performed on 362 patients with HFrEF. The baseline GNRI was calculated at the first visit. The patients were divided into three groups according to the GNRI: >98, no-risk group; 92 to ≤98, low risk group; 82 to <92, moderate­to­high­risk group. The study endpoint was a composite of follow-upCV events, including all-cause mortality, non-valvular atrial fibrillation (NVAF) , need for cardioverter defibrillator (ICD) therapy, HfrEF­related hospitalizations and need for percutaneous coronary interventions (PCIs). RESULTS: Follow-up data showed that the group with moderate-to-high risk had a significantly higher incidence of NVAF, PCIs and all-cause mortality compared to other groups (p<0.001, p: 0.026 and p0.05). Mean GNRI value was 83.3 in NVAF patients and 101.1 in patients without NVAF (p<0.001). Kaplan Meier survival analysis showed that patients from the group with moderate-to-high risk had a significantly worse survival rate (p < 0.001). In the multivariate Cox regression analysis, the group with moderate-to­high risk (HR=3.872) and ICD implantations (HR=4.045) were associated with increased mortality. CONCLUSION: The GNRI value may have a potential role for predicting future events, especially NVAF in patients with HfrEF (Tab. 4, Fig. 2, Ref. 27).

Photodynamic Therapy of Melanoma B16 with Chlorin E6 Conjugated with a PSMA-Ligand.

The efficacy of a new photosensitizer of chlorin E6 conjugated with a prostate-specific membrane antigen (PSMA) in photodynamic therapy of murine melanoma B16 was studied in in vivo experiments. The dynamics of photosensitizer accumulation in the tumor and surrounding tissues was evaluated and antitumor efficacy of photodynamic therapy was assessed by parameters of regression and morphological characteristics of experimental transplanted melanoma B16. The inhibitory effect of photodynamic therapy on melanoma was evaluated by complete regression of the tumor, absolute tumor growth coefficient in animals with continuation of tumor growth, and the increase in life span in comparison with the control; the criterion of cure was the absence of signs of tumor recurrence in mice within 90 days after therapy. The therapeutic potential of photodynamic therapy was determined by devitalization of tumor cells (histological examination of the zones of laser exposure on day 21 after treatment). The photosensitizer with PSMA-ligand exhibited high antitumor activity in photodynamic therapy for melanoma B16. Photodynamic therapy carried out at the optimum time after photosensitizer injection with experimentally determined parameters of laser exposure allows achieving the maximum inhibitory effect on melanoma. Pathomorphological study in the zones of exposure detected no survived tumor cells.

Photodynamic Therapy of Sarcoma M-1 in Rats with Photosensitizer Photoran E6.

We studied the effectiveness of photodynamic therapy with the photosensitizer Photoran E6 on the model of rat sarcoma M-1 positive for mutant p53 gene. Experiments showed that Photoran E6 exhibits high antitumor activity in photodynamic therapy of solid tumor of the connective tissue. Photodynamic therapy carried out during the optimal period after injections of Photoran E6 with the determined parameters of laser exposure allows achieving the maximum inhibitory effect on sarcoma M-1: 100% cured animals. Immunohistochemical study revealed no live tumor cells with expression of the mutant p53 protein in areas of photodynamic exposure.

Autoimmune and inflammatory manifestations in pediatric patients with primary immunodeficiencies and their importance as a warning sign.

INTRODUCTION AND OBJECTIVES: As well as increased susceptibility to infections, autoimmune and inflammatory manifestations also eventuate due to dysregulation of immune system in a substantial proportion of patients with primary immunodeficiency (PID). Autoimmune and inflammatory manifestations can occur prior or after diagnosis of PID. This study aimed to evaluate autoimmune and inflammatory complications among all types of PID patients in childhood and to emphasize the importance of these findings as a warning sign to diagnose PIDs. METHODS: Medical records of 1036 patients with PID, followed up between 2003 and 2019, were retrospectively screened for occurrence of autoimmunity and inflammation. During this time, demographic features, autoimmune/inflammatory findings and initial time, genetic mutations, laboratory and clinical follow up findings, treatment regimens and outcomes were recorded. RESULTS: Autoimmune and inflammatory manifestations were observed in 83 patients (10.1%). The median age of autoimmunity initial time was 61.3±53 months. Sixty-seven (80.7%) patients presented with autoimmune and inflammatory manifestations, and these findings had occurred during 16 patients' (19.3%) follow-up. The most common autoimmune manifestations were autoimmune hematologic (51.8%) and endocrine diseases (26.5%). Fifty patients (60.2%) had a single autoimmune/inflammatory manifestation, however 23 patients (27.7%) had two, eight patients (9.6%) had three and two patients (2.4%) had four different types of autoimmune/inflammatory manifestations. The frequency of autoimmune and inflammatory manifestations in phagocyte defects (56%), combined immune deficiencies (53%) and immune dysregulation diseases (52%) were observed higher than other forms of PIDs. During follow-up 13 (15.7%) patients died. CONCLUSION: Autoimmune/inflammatory manifestations are associated with high morbidity in patients with PIDs and may precede the diagnosis of PID in childhood. Therefore, physicians must be aware of underlying possible immune deficiency and patients with known PIDs should be evaluated for autoimmune and inflammatory complications.

Rare Tumours of the Testis: Twelve Years of Experience.

Rare tumours of the testis includes a wide variety of tumours. We aim to present clinical and histological characteristics of our patients with rare tumours of the testis. The medical records of 33 patients who were treated and followed-up for testicular rare tumours in our center between 2007 and 2020 were retrospectively reviewed. Of all the 243 testicular tumours, 222 cases (91.4%) were germ cell tumours and 21 cases (8.6%) were non-germ cell tumours. Thirty-three rare tumours of the testis including rare germ cell tumours and non-germ cell tumours were detected. The mean age of the patients at diagnosis was 34 years (range 18-68 years). The histological types of rare testicular tumours were as follows: teratoma 4.5% (n=11), sex-cord stromal tumours 4.5% (n=11), paratesticular tumours 3.2% (n=8), and the others [lymphoma 0.4% (n=1), mesothelioma 0.4% (n=1) and choriocarcinoma 0.4% (n=1)]. The median duration of follow-up was 32 months (range 1 to 256 months). None of the patients with non-metastatic disease stage developed recurrence after having received appropriate therapy. Metastatic disease was documented in 9 cases at the time of diagnosis (five patients with teratomas, two patients with Leydig cell tumour, one patient with choriocarcinoma and rhabdomyosarcoma). The most common subtypes of testicular rare tumours in our center was teratoma and sex-cord stromal tumours. Because of testicular rare tumours have different biological features and different clinical outcomes, the management of each tumour requires a different approach.

Monocyte/HDL ratio predicts hypertensive complications.

OBJECTIVE: We aimed to investigate whether a simple and easily calculated parameter such as monocyte/ HDL ratio (MHR) may be used in predicting non-dipper (NDHT)-dipper HT (DHT) end organ damage. METHODS: 70 NDHT and 73 DHT patient groups were included in the study according to ambulatory blood pressure screening results. Basic laboratory parameters and spot urine samples were evaluated. Transthoracic echocardiography and ophthalmological examination were performed for end-organ damages. RESULTS: The MHR among the groups was higher in the NDHT group; which was statistically significant (p≤0.001). In the NDHT group, albumin, creatinine, protein values, protein/creatinine ratio in the spot urine were significantly higher than in the DHT group (p≤0.05). Left ventricular hypertrophy (LVH) and retinopathy were also more frequently observed in the NDHT group (p≤0.001 and p=0.001, respectively). MHR in patients with LVH and retinopathy was significantly higher than in those without these complications (p=0.001). CONCLUSION: Easy to use, non-invasive and simple calculation, MHR can be used to predict end organ damage in hypertensive cases, and can be also used to distinguish between DHT/NDHT groups. This data supports the role of inflammation (Tab. 7, Ref. 14).

3D evaluation of tooth crown size in unilateral cleft lip and palate patients.

AIM: The aim of this retrospective study is to evaluate and compare the 3-dimensional (3D) crown sizes of the left and right sides of upper and lower dental arches in patients with unilateral cleft lip and palate (UCLP). MATERIALS AND METHODS: Dental casts of 94 patients all in permanent dentition were included in this study. Dental casts were divided into three groups as 36 casts with unilateral left cleft lip and palate (ULCLP), 18 casts with unilateral right cleft lip and palate (URCLP), and 40 casts without cleft (control). Mesiodistal (MD), buccolingual (BL), and gingiva incisal (GI) values of each tooth were measured by scanning the dental models with a high-precision optical 3D scanner. Paired t-test and independent t-test were used for statistical analysis. RESULTS: U1 MD, U6 MD (P = 0.001) and BL (P = 0.01), L3 GI (P = 0.05) were greater in UCLP patients on the non-cleft side while U1 GI, L1 BL, L5 MD (P = 0.001), L4 MD, and BL (P = 0.01) values were found to be greater on the cleft side. Comparison of the cleft-sides and the control group showed that MD, BL, and GI dimensions of teeth on the cleft sides were generally found to be smaller, excluding the UR7 GI values for URCLP group (P = 0.05). CONCLUSION: In the measurements of teeth size, reliable and repeatable results were acquired through 3D software. Tooth size asymmetries can occur non-syndromic UCLP patients in both jaws. MD, BL, and GI dimensions of teeth are mostly found to be smaller in patients with CLP.

Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development - the 2Close study: a multicentre randomised controlled trial.

BACKGROUND: Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility. METHODS: Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound. TRIAL REGISTRATION: Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.

The novel diagnostic marker in low-LVEF heart failure patients.

OBJECTIVE: The structural and compositional changes in the myocardium seem to have a major role in the development of heart failure (HF).Imbalance between production and degradation in extracellular collagen results in increase of collagen synthesis biomarkers in the circulation as the carboxy-terminal propeptide of type I procollagen (PIP). Here we aimed to determine role of PIP in the diagnosis of chronic HF. MATERIAL AND METHODS: 87 patients with HF group and 80 healthy subjects were enrolled into the study. Echocardiographic examination was performed.At the beginning of the study, serum B type natriuretic peptide (BNP), PIP, high sensitive C-reactive protein (hs-CRP) were measured . The subjects were followed for one year then after. RESULTS: Average PIP value of HF group was significantly higher than that of the control group (p < 0.001). Both hs-CRP and BNP values were well correlated to PIP values (p < 0.001). In the HF group, PIP value of patients who died at the end of one year was similar to that of patients who survived at the end of first year. CONCLUSION: PIP may not mirror acute events in follow-up of chronic heart failure but it is a very beneficial biomarker in diagnosis of low-LVEF heart failure with high sensitivity and specificity (Tab. 2, Fig. 1, Ref. 16).

Evaluation of pentraxin-3 in familial Mediterranean fever patients during attack and attack-free periods.

INTRODUCTION: Pentraxin-3 (PTX-3) is a prototype of pentraxin proteins that have been shown to be involved in acute phase response. In this study, we aimed to investigate the relationship between PTX-3 levels and familial Mediterranean fever (FMF) disease, and to evaluate PTX-3 as a novel diagnostic marker of FMF. METHOD: Forty-three male patients diagnosed with FMF and 42 healthy individuals were included in the study. Patients with other inflammatory diseases and patients who used drugs having anti-inflammatory properties were excluded from the research. Blood samples were obtained during both attack and attack-free periods. RESULTS: Patient attack periods were confirmed by combining physical examination and elevation of acute phase reactants. Acute phase reactants were significantly higher in attack versus attack-free periods (p < 0.01), however PTX-3 levels were not significantly different between the two periods. Additionally, PTX-3 levels in FMF patients were higher than in controls in both attack (917.29 ± 725.29 vs 451.83 ± 291.95, p < 0.01) and attack-free periods (748.23 ± 487.53 vs 451.83 ± 291.95, p < 0.01). CONCLUSION: In this study, we showed that PTX-3 levels, in both FMF attack and attack-free periods, were significantly higher than in the control group. Finally, PTX-3 may be a promising biomarker for FMF diagnosis and may predict FMF attacks (Tab. 2, Fig. 2, Ref. 18).

Laparoscopy in the management of lumboperitoneal shunt catheter in obese patients with pseudotumor cerebri.

Lumboperitoneal shunts are widely used for the treatment of patients diagnosed with pseudotumor cerebri (PTC). Obesity is a risk factor for PTC. In particular, catheter migration out of the abdominal cavity is more commonly observed in morbidly obese patients. The aim of this study was to discuss the underlying mechanisms of catheter migration and treatment modalities in morbidly obese patients with PTC. The present study included four morbidly obese patients. All cases had undergone the previous laparotomy for insertion of a distal catheter into the abdominal cavity. In three cases, migration of the distal catheter out of the abdominal cavity was observed. Migration of the proximal tip of the catheter out of the spinal canal was observed in the fourth case. In all cases, laparoscopic revision surgeries were performed. During revision surgery, a catheter tunnel was prepared immediately over the external oblique fascia to obtain the shortest and deepest tunnel, and a distal catheter was inserted by laparoscopic guidance posterolaterally, i.e., through the postaxillary line. None of the patients developed any complications during the follow-up period of 4 years. We recommend laparoscopic insertion of distal catheters through the postaxillary line into the abdominal cavity using as short a catheter route as possible. Thus, tension and traction on the catheter due to abdominal movements can be decreased in morbidly obese patients to prevent catheter migration.

An economic analysis of immediate delivery and expectant monitoring in women with hypertensive disorders of pregnancy, between 34 and 37 weeks of gestation (HYPITAT-II).

OBJECTIVE: To assess the economic consequences of immediate delivery compared with expectant monitoring in women with preterm non-severe hypertensive disorders of pregnancy. DESIGN: A cost-effectiveness analysis alongside a randomised controlled trial (HYPITAT-II). SETTING: Obstetric departments of seven academic hospitals and 44 non-academic hospitals in the Netherlands. POPULATION: Women diagnosed with non-severe hypertensive disorders of pregnancy between 340/7 and 370/7  weeks of gestation, randomly allocated to either immediate delivery or expectant monitoring. METHODS: A trial-based cost-effectiveness analysis was performed from a healthcare perspective until final maternal and neonatal discharge. MAIN OUTCOME MEASURES: Health outcomes were expressed as the prevalence of respiratory distress syndrome, defined as the need for supplemental oxygen for >24 hours combined with radiographic findings typical for respiratory distress syndrome. Costs were estimated from a healthcare perspective until maternal and neonatal discharge. RESULTS: The average costs of immediate delivery (n = 352) were €10 245 versus €9563 for expectant monitoring (n = 351), with an average difference of €682 (95% confidence interval, 95% CI -€618 to €2126). This 7% difference predominantly originated from the neonatal admissions, which were €5672 in the immediate delivery arm and €3929 in the expectant monitoring arm. CONCLUSION: In women with mild hypertensive disorders between 340/7 and 370/7  weeks of gestation, immediate delivery is more costly than expectant monitoring as a result of differences in neonatal admissions. These findings support expectant monitoring, as the clinical outcomes of the trial demonstrated that expectant monitoring reduced respiratory distress syndrome for a slightly increased risk of maternal complications. TWEETABLE ABSTRACT: Expectant management in preterm hypertensive disorders is less costly compared with immediate delivery.

Anoperineal lesions in Crohn's disease: French recommendations for clinical practice.

BACKGROUND: Anoperineal lesion (APL) occurrence is a significant event in the evolution of Crohn's disease (CD). Management should involve a multidisciplinary approach combining the knowledge of the gastroenterologist, the colorectal surgeon and the radiologist who have appropriate experience in this area. Given the low level of evidence of available medical and surgical strategies, the aim of this work was to establish a French expert consensus on management of anal Crohn's disease. These recommendations were led under the aegis of the Société Nationale Française de Colo-Proctologie (SNFCP). They report a consensus on the management of perianal Crohn's disease lesions, including fistulas, ulceration and anorectal stenosis and propose an appropriate treatment strategy, as well as sphincter-preserving and multidisciplinary management. METHODOLOGY: A panel of French gastroenterologists and colorectal surgeons with expertise in inflammatory bowel diseases reviewed the literature in order to provide practical management pathways for perianal CD. Analysis of the literature was made according to the recommendations of the Haute Autorité de Santé (HAS) to establish a level of proof for each publication and then to propose a rank of recommendation. When lack of factual data precluded ranking according to the HAS, proposals based on expert opinion were written. Therefore, once all the authors agreed on a consensual statement, it was then submitted to all the members of the SNFCP. As initial literature review stopped in December 2014, more recent European or international guidelines have been published since and were included in the analysis. RESULTS: MRI is recommended for complex secondary lesions, particularly after failure of previous medical and/or surgical treatments. For severe anal ulceration in Crohn's disease, maximal medical treatment with anti-TNF agent is recommended. After prolonged drainage of simple anal fistula by a flexible elastic loop or loosely tied seton, and after obtaining luminal and perineal remission by immunosuppressive therapy and/or anti-TNF agents, the surgical treatment options to be discussed are simple seton removal or injection of the fistula tract with biological glue. After prolonged loose-seton drainage of the complex anal fistula in Crohn's disease, and after obtaining luminal and perineal remission with anti-TNF ± immunosuppressive therapy, surgical treatment options are simple removal of seton and rectal advancement flap. Colostomy is indicated as a last option for severe APL, possibly associated with a proctectomy if there is refractory rectal involvement after failure of other medical and surgical treatments. The evaluation of anorectal stenosis of Crohn's disease (ARSCD) requires a physical examination, sometimes under anesthesia, plus endoscopy with biopsies and MRI to describe the stenosis itself, to identify associated inflammatory, infectious or dysplastic lesions, and to search for injury or fibrosis of the sphincter. Therapeutic strategy for ARSCD requires medical-surgical cooperation.

Modifying Effect of Autotransfusion of Mesenchymal Stromal Cells on the Production of Reactive Oxygen Species and Cytokines by Mononuclear Cells in Patients with Chronic Heart Failure.

We studied in vivo modifying effect of autotransfusion of human bone marrow mesenchymal stromal cells on ROS generation and production of cytokines (TNFα,TNFß, IL-1α, IL-10, IFNγ, and GM-CSF) and PGE2 by mononuclear cells of patients (N=21) with chronic heart failure. These parameters were evaluated prior to (control) and after (immediately and on day 14) intravenous administration of stromal cells in doses of 100-200×106. Immediately after autotransfusion, significant increase of in vitro zymosan-induced chemiluminescence of blood mononuclear cells from 10 patients was observed. At later terms after autotransfusion (day 14), inhibition of chemiluminescent activity of blood mononuclear cells was revealed in 50% patients. We discuss possible mechanisms of involvement of transplanted autologous bone marrow mesenchymal stromal cells in reprogramming of blood mononuclear phagocytes from the pro- to anti-inflammatory phenotype under conditions of their in vivo interaction manifesting in transition from activation to inhibition of ROS-producing activity of macrophages and significant suppression of in vitro LPS-induced production of TNFα and GM-CSF by blood mononuclears against the background of significantly elevated TNFß, IL-10, and IL-1α concentrations.

Efficacy of photodynamic therapy for basal cell carcinoma using photosensitizers of different classes.

The paper presented results of photodynamic therapy for 139 patients with basal cell carcinoma. We conducted a study of the efficacy and safety of four methods of photodynamic therapy. There were used the following photosensitizers: photohem, photosens, photolon and photodithazine. Photodynamic therapy using photosensitizers of chlorine series (photolon and photoditazin) provides a better long-term results improving disease-free 3-year survival rate to 90.4% and 92.3%, respectively compared to 54.7% and 71.1% in groups, in which treatment was restricted by photohem and photosens.