Risk of Melanoma and Non-Melanoma Skin Cancer in Patients with Psoriasis and Psoriatic Arthritis Treated with Targeted Therapies: A Systematic Review and Meta-Analysis.

Targeted therapies represent major advancements in the treatment of chronic skin conditions such as psoriasis. While previous studies have shown an increased risk of melanoma and non-melanoma skin cancer (NMSC) in patients receiving TNF-α inhibitors, the risks associated with newer biologics (IL-12/23 inhibitors, IL-23 inhibitors, IL-17 inhibitors) and Janus kinase (JAK) inhibitors remain less known. Using a systematic and meta-analytical approach, we aimed to summarize the currently available literature concerning skin cancer risk in patients treated with targeted therapies. The MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched to find studies reporting the incidence rates (IR) of melanoma and NMSC in patients with psoriasis and psoriatic arthritis treated with biologics or JAK inhibitors. Nineteen studies were included in the analysis with a total of 13,739 patients. The overall IR of melanoma was 0.08 (95% CI, 0.05-0.15) events per 100 PYs and the overall IR of NMSC was 0.45 (95% CI, 0.33-0.61) events per 100 PYs. The IRs of melanoma were comparable across patients treated with IL-17 inhibitors, IL-23 inhibitors, and JAK inhibitors, while the IRs of NMSC were higher in patients treated with JAK inhibitors than in those treated with biologics. Prospective, long-term cohort studies are required to reliably assess the risks associated with novel targeted therapies.

The role of cyclins in the development and progression of prostate cancer.

The role of cyclins in hormone-dependent neoplasms is crucial in the development of the disease that is resistant to first-line therapy, as the example of breast cancer shows. However, in prostate cancer, cyclins are studied to a lesser extent. There are some well-described molecular pathways, including cyclins A1 and D1 signaling, however the role of other cyclins, e.g., D2, D3, E, and H, still requires further investigation. Recent studies indicate that cyclins regulate various cellular processes, not only the cell cycle. Furthermore, they remain in cross-talk with many other signaling pathways, e.g., MAPK/ERK, PI3K/Akt, and Notch. The androgen signaling axis, which is pivotal in prostate cancer progression, interferes with cyclin pathways at many levels. This article summarizes current knowledge on the influence of cyclins on prostate cancer progression by describing interactions between the androgen receptor and cyclins, as well as mechanisms underlying the development of resistance to currently used therapies.

Tissue Fillers for the Nasolabial Fold Area: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Tissue fillers injections remain to be one of the most commonly performed cosmetic procedures. The aim of this meta-analysis was to systematize and present available data on the aesthetic outcomes and safety of treating the nasolabial fold area with tissue fillers. We conducted a systematic review of randomized clinical trials that report outcomes concerning treatment of nasolabial fold area with tissue fillers. We searched the MEDLINE/PubMed, ScienceDirect, EMBASE, BIOSIS, SciELO, Scopus, Cochrane Controlled Register of Trials, CNKI and Web of Science databases. Primary outcomes included aesthetic improvement measured using the Wrinkle Severity Rating Scale score and Global Aesthetic Improvement Scale. Secondary outcomes were incidence rates of complications occurring after the procedure. At baseline, the pooled mean WSRS score was 3.23 (95% CI: 3.20-3.26). One month after the procedure, the pooled WSRS score had reached 1.79 (95% CI: 1.74-1.83). After six months it was 2.02 (95% CI: 1.99-2.05) and after 12 months it was 2.46 (95% CI: 2.4-2.52). One month after the procedure, the pooled GAIS score had reached 2.21 (95% CI: 2.14-2.28). After six months, it was 2.32 (95% CI: 2.26-2.37), and after 12 months, it was 1.27 (95% CI: 1.12-1.42). Overall, the pooled incidence of all complications was 0.58 (95% CI: 0.46-0.7). Most common included lumpiness (43%), tenderness (41%), swelling (34%) and bruising (29%). Tissue fillers used for nasolabial fold area treatment allow achieving a satisfying and sustainable improvement. Most common complications include tenderness, lumpiness, swelling, and bruising. LEVEL OF EVIDENCE II: "This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 ."

Relationship between bariatric surgery outcomes and the preoperative gastrointestinal microbiota: a cohort study.

BACKGROUND: The composition of the gastrointestinal microbiota is associated with obesity. We hypothesized that the gut microbiota influences the outcomes of bariatric surgery. OBJECTIVES: We aimed to analyze using oral swabs and stool samples the microbiota of patients with morbid obesity who were undergoing laparoscopic sleeve gastrectomy (SG). SETTING: A university hospital in Poland. METHODS: This prospective cohort study was conducted between November 2018 and June 2019. Participants underwent SG or no surgery (controls). Results were then analyzed as a group 1 (surgical participants who achieved a percentage of excess weight loss [%EWL] >50%), group 2 (surgical participants who achieved a %EWL <50%), and group 3 (nonsurgical controls). %EWL was measured 6 months following surgery. Before surgery, oral swabs were obtained and stool samples were provided. The endpoint was the composition of the gut microbiota. RESULTS: Group 1 comprised 19 participants, group 2 comprised 11 participants, and group 3 comprised 16 participants. No participants were lost to follow-up during the study. Participants in group 1 had an oral microbiota that was enriched in the phyla Proteobacteria, and Bacteroidetes. Their intestinal microbiota was enriched in the Proteobacteria. In contrast, the oral microbiota of group 2 was enriched in the Actinobacteria and the intestinal microbiota was enriched in the phyla Bacteroidetes and Firmicutes. CONCLUSIONS: The compositions of the microbiota of the oral cavity and large intestine are related to the weight loss achieved following SG.

The Impact of Mobile Phone Use on Tinnitus: A Systematic Review and Meta-Analysis.

Tinnitus is a perception of sound in the absence of an external source. The aim of our study was to investigate with a meta-analytical approach, whether mobile phone (MP) use increases the risk of tinnitus. Eight studies reporting the risk of tinnitus in relation to MP use were identified, and six high-quality studies (two cohort studies, one case-control study, and three cross-sectional ones) were included in the meta-analysis. The quality assessment was performed using the Newcastle-Ottawa scale. The risk of tinnitus was analyzed depending on the exposure to MPs in subgroups according to the study design and method of exposure assessment. Two cohort studies, which assessed the exposure to MPs using network operator data, indicated no significantly increased risk of tinnitus among highly exposed MP users in comparison to lightly exposed individuals (odds ratio [OR]: 1.03 [95% confidence interval [CI]: 0.93-1.15]). Likewise, the self-reported exposure data from two cohorts/case-control and four cross-sectional studies did not find an association between exposure to MPs and tinnitus (OR: 1.20 [95% CI: 0.40-3.61] and OR: 1.73 [95% CI: 0.67-4.49], respectively). Current scientific knowledge, including high-quality studies with a reliable exposure assessment based on network operator data, does not support the hypothesis that MP use is associated with tinnitus. © 2020 Bioelectromagnetics Society.

Does Postoperative Oral and Intestinal Microbiota Correlate with the Weight-Loss Following Bariatric Surgery?-A Cohort Study.

The composition of the gastrointestinal microbiota is associated with obesity. The aim of this study was to verify if, six months after bariatric surgery, patients who achieve satisfying weight-loss after sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) have a different composition of oral and intestinal microbiota in comparison with those who do not. This prospective cohort study was conducted between November 2018 and November 2020. Participants underwent either SG or RYGB and were allocated into: Group 1-participants who achieved a percentage of excess weight loss (%EWL) of ≥ 50%, and Group 2-patients with %EWL of < 50%. The %EWL was measured 6 months following surgery. At this time, oral swabs were obtained and stool samples were provided. The endpoint was the composition of the gut microbiota. Group 1 comprised 20 participants and Group 2 comprised 11 participants. Group 1 had oral microbiota more abundant in phylum Fusobacteria and intestinal microbiota more abundant in phylum Firmicutes. Group 2 had oral microbiota was more enriched in phylum Actinobacteria and intestinal microbiota was more enriched in phylum Bacteroidetes. The compositions of the microbiota of the oral cavity and large intestine 6 months after bariatric surgery are related to the weight-loss.

Arterial resections in pancreatic cancer - Systematic review and meta-analysis.

BACKGROUND: The number of pancreatic resections due to cancers is increasing. While concomitant venous resections are routinely performed in specialized centers, arterial resections are still controversial. Nevertheless they are performed in patients presenting with locally advanced tumors. Our aim was to summarize currently available literature comparing peri-operative and long-term outcomes of arterial and non-arterial pancreatic resections. METHODS: We included studies comparing pancreatic operations with and without concomitant arterial resection. Inclusion criteria were morbidity or mortality. Studies additionally reporting venous resections with no possibility of excluding this data during the extraction were discarded. RESULTS: The initial search yielded 1651 records. Finally, 19 studies were included in the analysis involving 2710 patients. Arterial resection was associated with a greater risk of death(RR: 4.09; p < 0.001) and complications (RR: 1.4; p = 0.01). There were no differences in the rate of pancreatic fistula, biliary fistula rate, cardiopulmonary complications, length of hospital stay and non-R0 rate. Oncologically, patients after arterial resection were at higher risk of worse 3-year survival. CONCLUSION: Arterial resection in pancreatic cancer is associated with an increased risk of mortality and complications in comparison to standard non-arterial resections. Nevertheless, arterial resection may become a viable treatment for selected patients in high volume centers.

Variations and morphometric features of the vermiform appendix: A systematic review and meta-analysis of 114,080 subjects with clinical implications.

Determining the true and indisputable data regarding the vermiform appendix (VA) morphology is of a great clinical interest. The aim of this study was to provide the best evidence-based anatomical overview of the variations in location and size of VA using a systematic and meta-analytical approach. A systematic review with meta-analysis was performed of studies reporting variants of the location and morphometric data regarding the VA. The MEDLINE/PubMed, ScienceDirect, EMBASE, BIOSIS, SciELO, and Web of Science databases were thoroughly searched throughout June 2018. The reported locations of the body of the VA were re-classified into a new, standardized classification system divided into nine categories. The AQUA tool was used to assess the quality of included studies. The research was conducted following PRISMA guidelines and registered at PROPSERO database. Our meta-analysis included 242 studies (n = 114,080). Overall, the VA was most commonly found in the retrocecal location (32.1%, 95%CI: 29.2-35.1), followed by the pelvic (28.5%, 95%CI: 26.7-30.4) and ileal (14.5%, 95%CI: 11.8-17.7) locations. Subjects without known appendiceal pathologies had significantly smaller VA outer diameters (5.84 mm, 95%CI: 5.68-5.99) than patients diagnosed with acute appendicitis (10.64 mm, 95%CI: 10.14-11.15). The overall pooled mean length of the VA was 80.29 mm (95%CI: 76.68-83.89). Significant differences were found in size of the VA between imaging modalities. The results obtained from this evidence-based anatomy study will improve the clinical understanding of the VA anatomy, which in turn will have major implications for clinical practice. Clin. Anat. 32:85-98, 2019. © 2019 Wiley Periodicals, Inc.

Clinical outcomes and plasma clot permeability and lysability in patients with venous thromboembolism on rivaroxaban: a cohort study.

INTRODUCTION: Denser fibrin structure and impaired fibrinolysis reported in patients following venous thromboembolism (VTE) can predict recurrent VTE after cessation of anticoagulation. OBJECTIVES: The aim of the study was to investigate whether the properties of fibrin clot may be useful in predicting adverse events in patients with VTE receiving rivaroxaban. PATIENTS AND METHODS: In 132 patients with VTE treated with rivaroxaban for 8 weeks or longer, we determined plasma clot permeability (Ks) and clot lysis time (CLT) in blood samples collected 2 to 28 hours after rivaroxaban intake (20 mg/d). The primary endpoint was a composite of major and clinically relevant nonmajor bleeding, while the secondary endpoint was recurrent symptomatic VTE. RESULTS: During a median follow­ up of 32 months, the annual rates of primary and secondary endpoints were 3.6% and 2.7%, respectively. There were no differences in Ks and CLT between individuals who experienced the primary endpoint and the remainder. Patients with recurrent VTE had lower baseline Ks (-26.7%) and prolonged CLT (+20.8%) on rivaroxaban, without differences in rivaroxaban concentrations at the time of blood collection. After adjustment for confounding factors, Ks was the only predictor of VTE recurrence on rivaroxaban (odds ratio, 0.23; 95% CI, 0.06-0.94). CONCLUSIONS: Our study suggests that Ks assessed on rivaroxaban may provide prognostic information about the risk of recurrent VTE in anticoagulated patients.

Genetic Profile and Clinical Implications of Hepatoblastoma and Neuroblastoma Coexistence in a Child.

The aim of the following case report is to provide a description of the coexistence of two independent tumors in a child. A 9-month-old male was referred to Department of Pediatric Oncology and Hematology with hepatic tumor present on ultrasound imaging and symptoms of enlarged abdominal circumference. Physical examination revealed a palpable epigastric mass and the imaging techniques showed a tumor of the left hepatic lobe measuring 11 × 6.5 × 8.9 cm with pancreas infiltration, distant metastases in both lungs and abnormal lesion in the left adrenal gland. Basing on histopathological examination, after a core-needle biopsy, hepatoblastoma (HBL) (mixed epithelial-mesenchymal subtype) was diagnosed. The α-fetoprotein level was 112 993 ng/ml. Elevated values of normetanephrine, 3-methoxytyramine as well as neuron-specific enolase were observed. Due to the clinical picture and diagnosis, the patient was qualified to preoperative chemotherapy according to the SIOPEL-3 protocol, followed by SIOPEL-4 protocol for the high-risk patients. After undergoing preoperative chemotherapy, imaging tests revealed regression of hepatic tumor and no focal pulmonary masses, while regression of adrenal gland mass was not completed. The patient was qualified for left hemihepatectomy with left adrenalectomy. Histopathological examination of liver specimen confirmed the HBL diagnosis. However, in left adrenal gland and paraaortic lymph nodes the residual neuroblastoma (NBL) cells were detected. Whole exome sequencing (WES) was utilized to identify disease-associated germline mutations. WES revealed a novel germline insertion variant in TWIST1 (p.Gly86dup), along with the potentially pathogenic non-synonymous variants in NF1 (p.Val2511Ile), RAF1 (p.Leu445Arg), and WHSC1 (p.Ser4Asn) genes. Currently, 6 months after completion of treatment according to the SIOPEL-4 protocol, the patient is in good general condition, without any signs, and symptoms of relapse of both neoplasms. The coexistence of two different primary childhood malignancies is rarely seen. So far, only one case of synchronous HBL and NBL has been reported. However, for the first time therapeutic process was successful. A specific signature of rare germline mutations can be proposed as a predisposing factor to synchronous HBL and NBL occurrence.

Challenges associated with bariatric surgery - a multi-center report.

INTRODUCTION: Due to the constantly growing demand for surgical treatment of obesity, it is necessary to create new bariatric centers and further improve presently active ones. AIM: To identify which stages of conducting peri-operative care and organizing a modern bariatric center currently pose the greatest challenge. MATERIAL AND METHODS: An anonymous survey was designed and distributed to bariatric surgeons. Our questionnaire was divided into three parts: demographic characteristics, difficulties associated with peri-operative care for bariatric patients (assessed on a scale of 1-5) and difficulties associated with organization or running of bariatric centers in which participants are currently working (assessed on a scale of 1-5). RESULTS: Overall, 70 surgeons and surgical residents from 17 surgical centers participated in our survey. The most difficult element of the pre-operative care was compliance with the recommendation to cease smoking (3.47 ±1.28). The most difficult obstacle during the postoperative care period was implementation of the enhanced recovery after surgery (ERAS) protocol (2.27 ±1.31). Funding for the bariatric treatment was obtained exclusively from the National Health Fund by 60 (85.7%) respondents working in 15 different bariatric centers (88.2%). Among elements of bariatric infrastructure access to operating theater equipment sized for morbidly obese patients was reported to be the most difficult (3.8 ±1.68). CONCLUSIONS: Pre-operative recommendations including smoking, physical activity or weight loss, as well as introducing ERAS protocol based peri-operative care, are difficult to execute in bariatric departments. Future specialized bariatric centers should be included in the centralized register and equipped with specialized infrastructure for morbidly obese patients.