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The last 30 years have seen a revolution in the provision of minimal access surgery for many conditions, and technological advances are increasing exponentially. Many instruments are superseded by improved versions before the NHS and publicly funded health services can offer widespread coverage. Although we tend to think of minimal access surgery as a modern concept, Parts I and II of this series have shown that there is a 5000-year history to this specialty and our predecessors laid down many principles which still apply today. During the 19th and early 20th centuries, minimal access surgery was driven forward by visionary individuals, often in the face of opposition from colleagues and the medical establishment. However, in the last 30 years, innovation has been driven more in partnerships between healthcare, scientific, financial, educational and charitable organisations. There are far too many individuals involved to detail every contribution here, but this third part of the series will concentrate on some of the important themes in the development of minimal access surgery to its current status.

The neuraminidase (NA) of influenza A and B viruses plays a distinct role in viral replication and has a highly conserved catalytic site. Numerous sialic (neuraminic) acid analogs that competitively bind to the NA active site and potently inhibit enzyme activity have been synthesized and tested. Four NA inhibitors are now licensed in various parts of the world (zanamivir, oseltamivir, peramivir, and laninamivir) to treat influenza A and B infections. NA changes, naturally occurring or acquired under selective pressure, have been shown to reduce drug binding, thereby affecting the effectiveness of NA inhibitors. Drug resistance and other drawbacks have prompted the search for the next-generation NA-targeting therapeutics. One of the promising approaches is the identification of monoclonal antibodies (mAbs) targeting the conserved NA epitopes. Anti-NA mAbs demonstrate Fab-based antiviral activity supplemented with Fc-mediated immune effector functions. Antiviral Fc-conjugates offer another cutting-edge strategy that is based on a multimodal mechanism of action. These novel antiviral agents are composed of a small-molecule NA inhibitor and an Fc-region that simultaneously engages the immune system. The significant advancements made in recent years further support the value of NA as an attractive target for the antiviral development.

Background Neutrophilic dermatosis of the dorsal hands is an uncommon localised variant of Sweet syndrome first described in 1995. It is characterised by tender erythematous plaques, pustules and bullae on the dorsa of the hands. Literature Review A total of 123 cases of NDDH are included in this review. The mean patient age was 62.1 years and there was a slight female preponderance. 78.0% of cases had reported bilateral involvement and other sites were affected in almost a third of cases. Underlying disease was found in around 40% of patients, with the most common associations being haematological disorders (gammopathies, myelodysplasias or malignancies), recent infection, solid organ tumours and inflammatory bowel disease. Systemic and/or topical corticosteroids were employed in the treatment of 88.1% of cases while dapsone, colchicine and tetracyclines were the commonest steroid-sparing agents used. Improvement was often rapid and complete resolution the norm. Conclusions Whilst being uncommon, NDDH is frequently misdiagnosed and thus, its exact prevalence is probably underestimated. This may have significant implications including treatment delays or incorrect management. Moreover, recognition of NDDH is important since a correct diagnosis should trigger a search for underlying diseases and proper treatment with corticosteroids and/or steroid-sparing agents which is almost invariably curative.

Background Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase (BTK) that is FDA-approved for several lymphoproliferative disorders and chronic GVHD. Objective To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor inhibitor (EGFRi)-induced dermatologic adverse events (dAEs). Methods Single-center retrospective cohort of patients referred to the Skin Toxicities Program for management of cutaneous eruptions while taking ibrutinib. Results Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. The majority of patients were able to continue ibrutinib therapy with focused management of their cutaneous toxicities. Limitations This study represents cases at a single tertiary care center and is limited to patients referred for toxicity. Conclusions With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor-induced cutaneous adverse events.

Environmental awareness consists in the way human beings understand the environment. We observe that relation between humans and the natural environment is a concern related to the currently environmental and social. Thus, this paper aims to identify what we call as environmental perception in students from a 6th grade elementary state school in Sorriso, Mato Grosso. For this case study, we used a semi structured questionnaire with open and closed questions for a group of 63 students. After the answer’s analysis phase, for some previously selected questions, were created categories and tabulated, for other questions, data’s were analyzed and demonstrated in charts. As results, as quoted by several authors, we observed that the environmental and sight perception of the students are coherent for schoolchildren in this age, however, the authors reinforce that the development of projects concerning environmental education are still needed., A percepção ambiental consiste na forma como o ser humano compreende o meio ambiente. Observando a relação do homem com o ambiente natural é uma preocupação pertinente ao quadro ambiental e social, o presente trabalho tem como objetivo identificar aquilo que chamamos de percepção ambiental de alunos de 6° ano do ensino fundamental de uma escola estadual de Sorriso, Mato Grosso. Para este estudo de caso, foi utilizado um questionário semiestruturado com perguntas fechadas e abertas, para um grupo de 63 estudantes. Após a análise do conteúdo das respostas, para algumas questões previamente selecionadas, foram criadas categorias e tabeladas, para outras, os dados foram analisados e demonstrados em tabelas. Foi possível observar que a percepção ambiental dos alunos e a visão de meio ambiente é coerente com o citado por diversos autores para estudantes dessa idade, no entanto, reforçam que ainda há uma necessidade de desenvolvimento de projetos voltados à educação ambiental.

Background Early specialist evaluation during rapid proliferative growth of complicated infantile hemangiomas (IH) is crucial. Health disparities and barriers of access-to-care for children with IH have not been examined. Objective Investigate whether socioeconomic status (SES) is associated with age at subspecialist presentation for IH evaluation. Method Retrospective cohort study of 804 children presenting to a large academic hospital. Primary outcome was age at initial presentation. Covariates included demographic, socioeconomic, geographic, and clinical characteristics. Medicaid or Children's Health Insurance Program (CHIP) were proxies for lower SES. Analysis of covariance, χ2 tests, and generalized ordered logistic regressions were performed. Results Children with lower SES had higher odds of presenting after 3 months of age (OR 2.11, 95% CI 1.31-3.38). In the subset that qualified for institutional care management program (ICMP), no risk factors were associated with delayed presentation. Limitations Use of insurance and economic distress as proxies for SES; exclusion of uninsured children may underestimate racioethnic effects; single academic center study limiting generalizability. Conclusions Children with IH and lower SES were more likely to present later to specialists, but those enrolled in an ICMP did not, suggesting that integrated ICMPs may mitigate disparities and delayed access-to-care for IH among lower SES populations.

The United States population is aging and increasing in comorbidity, and patient care is accordingly growing increasingly complex. Complexity impacts patterns of resource consumption, adverse event and medical error rates, health-related quality of life, physician burnout, and more. Tools capturing complexity can be of benefit in the modern value-based reimbursement landscape and have been well-studied in specialties other than dermatology. In this paper, we describe the validation of a tool specific to outpatient dermatologic care that captures the complexity of clinical visit medical decision-making. We performed a cross-sectional retrospective study to determine the inter-rater reliability and face validity of the tool. By objectively grading a clinical encounter based on clinical complexity, there is increased awareness of opportunities to improve clinical care and the allocation of healthcare costs and resources within the dermatologic community can be better assessed.

ZusammenfassungIn jüngster Zeit wurden in der Therapie der eosinophilen Ösophagitis (EoE) und insbesondere im Bereich der topischen Corticosteroide erhebliche Fortschritte erreicht. Neue EoE-spezifische Darreichungsformen wurden entwickelt und haben in Form der orodispersiblen Budesonid-Tablette zu der ersten in Deutschland und anderen europäischen und außereuropäischen Ländern zugelassenen Therapie der EoE bei Erwachsenen geführt. In den USA steht eine EoE-spezifische orale Budesonid-Suspension kurz vor der Zulassung. Dagegen bleibt die wissenschaftliche Datenlage zur Wirksamkeit von Protonenpumpeninhibtoren weiterhin limitiert. Auch im Bereich der Biologika konnten nach langer Zeit Substanzen identifiziert werden, die erstmals in Phase 2 sehr vielversprechende Ergebnisse gezeigt haben und sich derzeit in klinischen Prüfungen der Phase 3 befinden. In diesem Artikel sollen die aktuellen Fortschritte und Perspektiven in der Therapie der EoE dargestellt und diskutiert werden.

Background Non-physician practitioners (NPPS), including nurse practitioners (NPs) and physician assistants (PAs) are expanding their scope of practice outside of primary care and performing more procedures in dermatology. Objective To understand the scope and geographic pattern of practice by NPs and PAs in dermatology in the US. Methods Cross-sectional retrospective cohort analysis of dermatology practices in the 2014 Medicare Physician/Supplier Procedure Summary Master File, which reflects Part B carrier and durable medical equipment fee-for-service claims in the US. Results Over 4 million procedures were billed independently by NPs and PAs, which accounts for 11.51% of all. Injection, simple repair, and biopsy were the most commonly billed by non-physician practitioners, but complex procedures were also increasingly billed independently by NPs and PAs. Proportions of their claims are higher in the East Coast, Midwest, and Mountain states. Limitations Data is at the state level, limited to Medicare beneficiaries, and doesn’t include billing incident-to physicians. Conclusions This study demonstrated the increasing scope of practice of NPs and PAs in dermatology, despite limited training and lack of uniform regulations. To ensure quality and safety of care, it is prudent to set benchmarks for proper supervision and utilization of procedures in dermatology.

Background To date, there is no comprehensive meta-analysis analyzing the association between alopecia areata, anxiety, and depression. Objective We sought to analyze the existing literature to examine the association between alopecia areata, anxiety, and depression. Methods We extracted literature from four databases including Medline, Embase, PsychINFO, and Web of Science. We utilized the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines in order to finalize a list of relevant articles to be included in our systematic review and meta-analysis. There were no restrictions placed on publication year or age of participants. Results A total of 8 studies that included 6,010 patients with AA and 20,961 control patients were included in the quantitative analysis. These included 4 cross-sectional studies and 4 case-control studies. Analysis of these studies demonstrated a positive association with anxiety (pooled OR, 2.50; 95% CI, 1.54-4.06) and depression (pooled OR, 2.71; 95% CI, 1.52-4.82). Limitations Publication bias may be a limitation of the study. Conclusion This study suggests that patients with AA are at higher risk of both anxiety and depression. Healthcare professionals must be cognizant of this higher risk and consider routine assessment of these conditions and referral to appropriate providers when indicated.

Background Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

Dua prinsip yang saling bertentangan tentang hukum tanah yang mengatur sebelum terbentuknya Undang-Undang Nomor 5 Tahun 1960 tentang Pokok-Pokok Hukum Agraria, di mana perbedaan aturan hukum bagi orang Indonesia dan bukan orang Indonesia terkait dengan hak tanah menjadikan dasar penggagas yang mendasar sebagai negara hukum untuk dibentuk suatu aturan hukum yang pasti yang berkaitan dengan pertanahan di negara Indonesia. Alasan dari pengambilan judul ini untuk mengkaji dan memberikan wawasan di bidang agraria dalam hak penguasaan tanah di Indonesia serta ketimpangan yang terjadi dalam masyarakat luas. Penulisan jurnal ini menggunakan penelitian hukum normatif atau studi kepustakaan, karena kajian yang diperoleh berdasarkan referensi dari buku-buku, artikel, maupun peraturan-peraturan yang berkaitan dengan hukum agraria atau kebijakan pertanahan. Berbagai hak penguasaan atas tanah yang diatur dalam Undang-Undang Nomor 5 Tahun 1960 tentang Pokok-Pokok Hukum Agraria yang dibentuk dengan tujuan meletakkan dasar-dasar bagi penyusun hukum agraria nasional yang merupakan sarana untuk mengupayakan sebesar-besarnya kemakmuran, kebahagiaan dan keadilan bagi rakyat, tidak selaras atau berhubungan dengan apa yang terjadi pada situasi sekarang. Sehingga terjadi ketimpangan dalam penguasaan tanah, baik itu orang, korporasi maupun pemerintah. Kata Kunci: hak, penguasaan, tanah, ketimpangan.

ZusammenfassungEine Beteiligung des Ösophagus bei der Hauterkrankung Lichen planus wurde erstmals 1982 beschrieben und fast 30 Jahre lang als eine Rarität angesehen. Untersuchungen der letzten 10 Jahre aber zeigen, dass diese Erkrankung weniger selten ist als angenommen. Es ist sogar anzunehmen, dass der ösophageale Lichen planus (Esophageal Lichen planus, ELP) häufiger ist als die Eosinophile Ösophagitis (EoE). Die Ösophagusbeteiligung betrifft meist Frauen im mittleren Alter. Das Hauptsymptom ist eine Dysphagie. Endoskopisch erkennt man in der Speiseröhre eine charakteristische Schleimhautablösung, eine Trachealisierung, und gelegentlich Hyperkeratosen und bei langem Bestehen auch Stenosen. Wegweisend ist die Histologie mit einer subepithelialen Ablösung sowie einem bandförmigen Infiltrat aus T-Lymphozyten, dem Nachweis von apoptotischen Keratinozyten (Civatte Bodies) und Dyskeratosen. Die direkte Immunfluoreszenz zeigt Fibrinogen-Ablagerungen entlang der Basalmembran. Eine etablierte Therapie gibt es bisher nicht. Die Behandlung mit topischen Steroiden ist in 2/3 der Fälle wirksam. Eine Therapie wie beim klassischen Lichen planus scheint unwirksam zu sein. Bei symptomatischen Stenosen kann eine Dilatation indiziert sein. Der ELP reiht sich in die Gruppe der „neuen“ immunologisch vermittelten Erkrankungen des Ösophagus ein.

Lysosomal acid lipase (LAL) deficiency is a rare, autosomal recessive disease caused by mutations in the LIPA gene, which produces cholesteryl ester and triglyceride accumulation predominantly in hepatocytes, adrenal glands, and gastrointestinal tract. We describe two new cases occurring in siblings, aged 5 and 7 years, who presented with hepatomegaly, dyslipidemia, and abnormal liver function. Percutaneous liver biopsy revealed portal inflammation, hypertrophic Kupffer cells with a foamy appearance and microvesicular steatosis with fibrosis. Immunostaining for lysosomal markers, cathepsin D and LAMP1 reflected the lysosomal nature of the lipid vacuoles. After enzymatic confirmation, enzyme replacement therapy was initiated for both siblings. Follow-up transaminase levels and lipid profiles showed a notable decrease in AST and ALT and a slight increase in HDL cholesterol. It is crucial to increase awareness of this rare condition among clinicians and pathologists. The expression of lysosomal markers around the lipid vacuoles might help diagnose LAL deficiency in pediatric patients.

Abstract: Carbon monoxide (CO) is endogenously produced upon degradation of heme by heme oxygenases (HOs) and is suggested to act as a gaseous signaling molecule. The expression of HO-1 is triggered by the Nrf2-Keap1 signaling pathway which responds to exogenous stress signals and dietary constituents such as flavonoids and glucosinolates or reactive metabolic intermediates like 4-hydroxynonenal. Endogenous CO affects energy metabolism, regulates the utilization of glucose and addresses CYP450 enzymes. Using the CO releasing molecule-401 (CORM-401), we studied the effect of endogenous CO on ATP synthesis, AMP-signaling and activation of the AMPK pathway in cell culture. Upon exposure of cells to CORM-401, the mitochondrial ATP production rate was significantly decreased (P=0.007) to about 50%, while glycolytic ATP synthesis was unchanged (P=0.489). Total ATP levels were less affected as determined by mass spectrometry. Instead, levels of ADP and AMP were elevated following CORM-401 exposure by about two- (P=0.022) and four-fold (P=0.012) compared to control, respectively. Increased concentrations of AMP activate AMPK which was demonstrated by a 10 to 15-fold increased phosphorylation of Thr172 of the α-subunit of AMPK (P=0.025). A downstream target of AMPK is the kinase ULK1 which triggers autophagic and mitophagic processes. Activation of ULK1 after CO exposure was proven by a 3 to 5-fold elevated phosphorylation of ULK1 at Ser555 (P=0.004). The present data suggest that production of endogenous CO leads to increasing amounts of AMP which mediates AMPK-dependent downstream effects and likely triggers autophagic processes. Since dietary constituents and their metabolites induce the expression of the CO producing enzyme HO-1, CO signaling may also be involved in the cellular response to nutritional factors.

Abstract: The effect of carvacrol (CAR) on oxidative stress, inflammation, and liver dysfunction induced by lipopolysaccharide (LPS) was explored. The rats (n=40) were daily injected (2 weeks) by saline as control, LPS (1 mg/kg, i.p.), and 25, 50 or 100 mg/kg CAR (i.p.) before LPS. LPS increased aspartate transaminase (AST: 162±13 U/L), alanine aminotransferase (ALT: 74.6±2.15 U/L), alkaline phosphatase (ALK-P: 811±51 U/L), interlukine-1β (IL-1β: 1254±51 pg/g tissue), malondialdehyde (MDA: 32±1.09 nM/g tissue), and nitric oxide (NO: 224±13.5 nM/g tissue) (P

Abstract: In this study, children with vitamin B12 deficiency anemia (V-B12DA) and control subjects were evaluated for erythrocyte glutathione peroxidase, catalase and superoxide dismutase enzyme activities, glutathione, malondialdehyde, serum total sialic acid, total antioxidant status, cobalt, chromium, copper, selenium, vanadium, zinc, iron, lead, magnesium, calcium, sodium, potassium, chloride, phosphorus levels, and the associations of these variables were assessed. The study included 50 children with V-B12DA and 50 control subjects. It was found that the V-B12DA group was significantly lower than the control group, with regard to the mean±the standard error of the mean levels of cobalt (0.089±0.009; 0.058±0.0063 μmol/L, p12 (427.20±21.45; 157.08±3.96 pg/mL, p12DA, significantly linear correlations were observed between cobalt – vitamin B12 (r=0.334; p=0.025), vanadium – MCV (r=0.315; p=0.017), vitamin B12 – MCV (r=−0.297; p=0.026). The findings of the study indicated that the levels of cobalt, vanadium significantly associated with traditional vitamin B12-deficiency parameters. Vitamin B12 and MCV should be measured together with cobalt, vanadium for monitoring the vitamin B12 deficiency anemia.

Leukemia and lymphoma are cancers affecting children, adolescents, and young adults and may affect reproductive outcomes and maternal metabolism. We evaluated for metabolic changes in newborns of mothers with a history of these cancers.A cross-sectional study was conducted on California births from 2007 to 2011 with linked maternal hospital discharge records, birth certificate, and newborn screening metabolites. History of leukemia or lymphoma was determined using ICD-9-CM codes from hospital discharge data and newborn metabolite data from the newborn screening program.A total of 2,068,038 women without cancer history and 906 with history of leukemia or lymphoma were included. After adjusting for differences in maternal age, infant sex, age at metabolite collection, gestational age, and birthweight, among newborns born to women with history of leukemia/lymphoma, several acylcarnitines were significantly (The varied metabolite levels suggest history of leukemia or lymphoma has metabolic impact on newborn offspring, which may have implications for future metabolic consequences such as necrotizing enterocolitis and urea cycle enzyme disorders in children born to mothers with a history of leukemia or lymphoma.

OBJECTIVE: To evaluate whether pathologic complete response (pCR) exclusively defines major pathologic response to treatment with improved survival. SUMMARY BACKGROUND DATA: pCR following trimodality therapy for esophagogastric adenocarcinoma is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint. METHODS: We analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adenocarcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage treatment response (TR) in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis. RESULTS: Among 788 patients, median follow-up was 37.5 months (range, 0.4–210.6); median OS was 48.3 months (95% CI, 42.2–58.8). Absence of residual nodal disease was independently associated with improved survival (P

Background Instrument oversupply drives cost in the operating room (OR). We review previously reported methodologies for surgical instrument reduction and report a pilot methodology for optimizing instrument supply via ethnographic instrument tracking of thumb carpometacarpal (CMC) arthroplasties. Additionally, we report a cost analysis of instrument oversupply and potential savings of tray optimization methods. Methods Instrument utilization was tracked over 8 CMC arthroplasties conducted by 2 surgeons at an ambulatory surgery center of a large academic hospital. An optimized supply methodology was designed. A cost analysis was conducted using health-system-specific data and previously published research. Results After tracking instrument use in 8 CMC arthroplasties, a cumulative total of 59 out of the 120 instruments in the Hand & Foot (H&F) tray were used in at least 1 case. Two instruments were used in all cases, and another 20 instruments were used in at least 50% of the cases. Using a reduced tray with 59 instruments, potential cost savings for tray reduction in 60 cases were estimated to be $2086 without peel-packing and $2356 with peel-packing. The estimated cost savings were lower than those reported in literature due to a reduced scope and exclusion of OR time cost in the analysis. Conclusions Instrument oversupply drives cost at our institution’s ambulatory surgery center. Ethnography is a cost-effective method to track instrument utilization and determine optimal tray composition for small services but is not scalable to large health systems. The time and cost required to observe sufficient surgeries to enable supply reduction to motivate the need for more efficient methods to determine instrument utility.

Background: Actionable feedback from patients after a clinic visit can help inform ways to better deliver patient-centered care. A 2-word assessment may serve as a proxy for lengthy post-visit questionnaires. We tested the use of a 2-word assessment in an outpatient hand clinic. Methods: New patients were asked to provide a 2-word assessment of the following: (1) their physician; (2) their overall experience; and (3) recommendations for improvement and their likelihood to recommend (LTR) after their clinic visit. Sentiment analysis was used to categorize results into positive, neutral, or negative sentiment. Recommendations for improvement were classified into physician issue, system issue, or neither. We evaluated the relationship between LTR status, sentiment, actionable improvement opportunities, and classification (physician issue, system issue, or neither). Recommendations for improvement were classified into themes based on prior literature. Results: Sixty-seven (97.1%) patients noted positive sentiment toward their physician; 67 (97.1%) noted positive sentiment toward their overall experience. About 31% of improvement recommendations were system-based, 5.9% were physician-based, and 62.7% were neither. Patients not LTR were more likely to leave actionable opportunities for improvement than those LTR ( P = .01). Recommendations for improvement were classified into predetermined themes relating to: (1) physician interaction; (2) check-in process; (3) facilities; (4) unnecessary visit; and (5) appointment delays. Conclusion: Patients not likely to recommend provided actionable opportunities for improvement using a simple 2-word assessment. Implementation of a 2-word assessment in a hand clinic can be used to obtain actionable, real-time patient feedback that can inform operational change and improve the patient experience.

Background: Gastric cancer (GC) is a common tumor found worldwide, and cisplatin is the first-line agent for the treatment of GC. However, the resistance to cisplatin is an obstacle. Here, we aim to explore the biological mechanism of long noncoding RNA regulator of reprogramming (ROR) in the cisplatin resistance of GC. Materials and Methods: ROR, miR-519d-3p, and high mobility group protein A2 (HMGA2) expression in GC tissues and cells were measured by quantitative real-time polymerase chain reaction and Western blot. Cell viability, migration, invasion, and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay, and flow cytometry, respectively. The relative protein expression was detected by Western blot. The interactions between miR-519d-3p and ROR, HMGA2 were predicted using miRcode and starBase v2.0 online database, and then verified by dual luciferase reporter assay and RNA immunoprecipitation assay. In addition, the xenograft tumor mouse model was constructed to verify the biological role of ROR in vivo. Results: The levels of ROR, HMGA2 were significantly upregulated, and miR-519d-3p was apparently downregulated in GC tissues and cells. The miRcode and starBase v2.0 online websites and dual luciferase reporter assay validated that miR-519d-3p directly interacted with ROR and HMGA2. Furthermore, ROR knockdown downregulated HMGA2 to restrain cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and cisplatin resistance in GC cells by targeting miR-519d-3p. In addition, the depletion of ROR repressed the xenograft tumor growth in vivo. Conclusion: In conclusion, we first found the ROR/miR-519d-3p/HMGA2 regulatory network to regulate cell proliferation, migration, invasion, EMT, and cisplatin resistance in GC, and this may shed light on the GC tumorigenesis.

Early diagnosis and adequate surgical treatment are the key factors for the course of the laryngeal cancer of the head and neck and the outcome of the surgical treatment in these patients. The aim of the paper is to compare the characteristics of the surgically treated patients with the larynx carcinoma who developed recidivism to those who did not. The study was done as a retrospective observational case-control study on a total of 90 patients with the laryngeal cancer who had been successfully operated on and whose cases had been followed over a period of at least five years after the surgery. After that, they were shorted into two groups based on the development of recidivism, and clinical characteristics of the patients with and without recidive disease were compared. 19 out of 90 patients developed recidivism. Maximum diameter of the tumour was significantly larger in patients without local recidivism. In patients without local recidivism, most common clinical stages were 3 and 4 (32.4%, 40.8%, respectively), whereas in patients with local recidivism stages 1 and 2 were the most common (47.7%, 26.3%, respectively). The average time to disease recurrence in the 19 patients who developed local recidive disease was 648.10 (384.67-911.54) days. Pathohistological analysis showed that samller the size of the tumour and lower T grade at the moment of surgery are precautionary factors for further monitoring of patients with laryngeal cancer.

Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Homocysteine (Hcy) has a detrimental influence on human neurons, considering that human GBM cells undergo cell death already at D,L-Hcy concentrations in culture medium of 50 μM. This data demonstrate that Hcy is a potent gliotoxic agent capable of inducing the death of human glial cells already at concentrations reached in brain during hyperhomocysteinemia. The one retrospective study found that the serum vitamin B12 level can be used to predict survival time in metastatic cancer patients including neurological cancer. Cancer risk increases with elevated vitamin B12 level, mostly within the first year of the follow-up period, suggesting that vitamin B12 level could be used as a cancer diagnostic marker. In addition, the relationship between elevated vitamin B12 level and poor cancer survival time has been reported. Previous investigation suggests that the folate supplementation could be used as an adjuvant in antiglioma therapy to limit the low DNA methylation level because this confers a poor prognosis in glioblastoma multiforme patients. Taking into account all presented data, it can be concluded that effect of homocystein, folic acid and vitamin B12 on formation, development and outcome of treatment in patients with carcinoma is very intriguing question, whose response requires additional both experimental and clinical research. There lack of data in the literature on the incidence of elevated levels of Hcy in the blood, as well as the disorders of folic acid and vitamin B12, at malignant tumors of the brain.

Background: The procancer effect of TEA domain transcription factor 4 (TEAD4) has been gradually discovered. However, its expression in esophageal cancer (EC) cells and its effect on proliferation ...

Background Effects of the major ginsenoside Rg1 on mammalian longevity and physical vitality are rarely reported. Purpose To examine longevity, tumor, and spontaneous locomotor activity in rats consuming Rg1. Methods A total of 138 Wistar rats were randomized into 2 groups: control (N = 69) and Rg1 (N = 69). Rg1 (0.1 mg/kg per day) were orally supplemented from 6 months of age until natural death. Spontaneous mobility was measured by video-tracking together with body composition (dual energy x-ray absorptiometry) and inflammation markers at 5, 14, 21, and 28 months of age. Results No significant differences in longevity (control: 706 days; Rg1: 651 days, p = 0.77) and tumor incidence (control: 19%; Rg1: 12%, p = 0.24) were observed between the two groups. Movement distance in the control group declined significantly by ∼60% at 21 months of age, together with decreased TNF-α (p = 0.01) and increased IL-10 (p = 0.02). However, the movement distance in the Rg1 group was maintained ∼50% above the control groups (p = 0.01) at 21 months of age with greater magnitudes of TNF-α decreases and IL-10 increases. Glucose, insulin, and body composition (bone, muscle and fat percentages) were similar for both groups during the entire observation period. Conclusion The results of the study suggest a delay age-dependent decline in physical vitality during late life by lifelong Rg1 consumption. This improvement is associated with inflammatory modulation. Significant effects of Rg1 on longevity and tumorigenesis were not observed.

Anaemia is a common complication of chronic kidney disease. The most important contributory factor is an abnormally low circulating concentration of erythropoietin, which is produced by the kidney peritubular cells. Anaemia of kidney disease is likely to develop once the glomerular filtration rate (GFR) is

Background The impact of online care on patients’ functional and psychological outcomes is critical to determine yet still unknown. Objective To evaluate how a novel online health model that facilitates physician-patient collaboration compares with in-person care for improving psoriasis patients’ functional status and mental health. Methods This 12-month randomized controlled equivalency trial randomized psoriasis patients 1:1 to online or in-person care. Functional impairment and depression were assessed at baseline and at 3-month intervals using the 5-level EuroQol-5 Dimensions (EQ-5D-5L) and Patient Health Questionnare-9 (PHQ-9). Results 296 patients were randomized to online or in-person groups. The between-group difference in overall improvement in EQ VAS (EuroQol Visual Analogue Scale) was -0.002 (95% CI -2.749, 2.745), falling within equivalence margin ±8. The between-group difference in overall improvement in EQ-5D-5L index was 0 (95% CI -0.003, 0.003), falling within equivalence margin ±0.1. The between-group difference in overall improvement in PHQ-9 was -0.33 (95% CI -1.20, 0.55), falling within equivalence margin ±3. Limitations Slightly different attrition rates between online and in-person arms (11% versus 9%), but no impact on outcomes. Conclusion The online health model was equivalent to in-person care for reducing functional impairment and depressive symptoms in psoriasis patients.

Laparoscopic surgery is currently established as the primary modality for many procedures. In has been associated with a number of benefits over traditional open surgery, including reduced pain, shorter hospital stay and quicker return to work. Despite this, significant operative challenges and the potential for life-threatening complications exist. Surgeons must understand the specialist equipment that is required, along with how to troubleshoot common issues. Furthermore, an appreciation of the distinctive surgical techniques and technical challenges is critical in limiting the risk of significant complications. Through this article we discuss these topics in the context of the current literature, aiming to recognize common pitfalls that all surgeons should make a conscious effort to avoid. We will describe those patient groups, specifically obesity, pregnancy, elderly and bowel obstruction, in whom additional caution must be maintained. Finally, we will consider these principles in the context of the wider field of minimally invasive surgery, to include robotics, single incision, transanal microsurgery (TAMIS) and transanal total mesorectal excision (TaTME). Although the landscape of minimally invasive surgery is constantly evolving, a robust understanding of the underlying principles is essential for all surgeons.

Background and Objectives The literature supporting Mohs micrographic surgery and staged excision in treating primary cutaneous melanoma is growing but has not been critically reviewed for bias. Methods Articles concerning Mohs micrographic surgery and staged excision for melanoma were assessed using modified “Risk of Bias in Non-randomized Studies of Interventions” (ROBINS-I) criteria, which measures bias in 7 categories. Results Forty-seven of 48 (97.9%) studies reviewed had serious or critical bias. None were randomized controlled trials. The most frequent cause of critical bias was poorly defined outcomes. The least frequent form of bias observed was change in intervention. Limitations The modified ROBINS-I criteria cannot account for all study limitations. Modification of the criteria leads to some degree of subjectivity. Conclusion The current body of literature suffers from limitations due to serious or critical bias in 1 or more ROBINS-I criteria. Local recurrence rate definitions are often poorly defined or not defined at all. Longer follow-up times, clear tumor classifications, and prospective, randomized study designs are necessary to improve the quality of future research.

Background Most children with atopic dermatitis(AD) suffer from sleep disturbance, but reliable and valid assessment tools are lacking. Objectives To test PROMIS (Patient Reported Outcomes Measurement Information System) sleep measures in pediatric AD and to develop an algorithm to screen, assess and intervene to reduce sleep disturbance. Methods A cross-sectional study was conducted with AD children ages 5-17 years and one parent(n=61), who completed sleep, itch, and AD-specific questionnaires; clinicians assessed disease severity. All children wore actigraphy watches for 1-week-objective sleep assessment. Results PROMIS sleep disturbance parent-proxy-reliability was high (Cronbach's α=0.90) and differentiated among Patient Oriented Eczema Measure (POEM)-determined disease severity groups (mean±SD in mild vs. moderate vs. severe was 55.7±7.5 vs. 59.8±10.8 vs. 67.1±9.5, p Limitations This was a local sample. Conclusions Sleep disturbance in pediatric AD should be screened using the POEM sleep question, with further assessment using the PROMIS sleep disturbance measure or objective sleep monitoring if needed.

Abstract. Purpose: Teas are an essential part of traditional phytotherapy. The aim of this systematic review is to assess the clinical evidence using green tea catechins in cancer care. Methods: A systematic search was conducted searching five electronic databases concerning the effectiveness and risks of epigallocatechin gallate (EGCG) on cancer patients. Results: Seven studies with 371 patients were included. Patients were mainly suffering from breast and prostate cancer. Dosing ranged from 28 mg to 1600 mg EGCG, intervention time from 7 days to 6 months with different applications (topical 2 studies; oral 5 studies). The studies showed heterogeneous methodological quality and results leading not to conduct a meta-analysis. There was a small decrease in prostate-specific-antigen levels in one study (N=60; T0:(mean±SD) 9.6±5.2 ng/ml, T1: 8.4±4.3 ng/ml vs. T0: 9.9±8.5 ng/ml, T1: 10.0±9.0 ng/ml; p=0.04), whereas in a second study only a trend was seen. Topical green tea was as effective as metronidazole powder in reducing the odor of fungating malignant wounds (1 study; N=30) with a consequent increase in quality of life (QoL) (p

Background Lentigo maligna/lentigo maligna melanoma (LM/LMM) can present with subclinical extension that may be difficult to define preoperatively and lead to incomplete excision and potential recurrence. Preliminarily studies have used reflectance confocal microscopy (RCM) to assess LM/LMM margins. Objective To evaluate the correlation of LM/LMM subclinical extension defined by RCM compared to the gold standard histopathology. Methods Prospective study of LM/LMM patients referred for dermatologic surgery. RCM was performed at the clinically-defined initial surgical margin followed by margin-controlled staged excision with paraffin-embedded tissue and histopathology was correlated with RCM results. Results Seventy-two patients were included. Mean age was 66.8 years (SD 11.1; 38 – 89 years); 69.4% were males. 70/72 (97.2%) lesions were located on the head neck with mean largest clinical diameter of 1.3cm (0.3 – 5 cm). Diagnostic accuracy for detection of residual melanoma in the tumor debulk (after biopsy) had a sensitivity of 96.7% and a specificity of 66.7% when compared to the histopathology. RCM margin assessment revealed an overall agreement with final histopathology of 85.9% (kappa 0.71; p Limitations No RCM imaging beyond initial planned margins was performed. Conclusion RCM showed moderate to excellent overall agreement between RCM imaging of LM/LMM and histopathology of staged excision margins.

No surgery is ever free of the risk of a complication. As the number of surgeries increase annually, the incidence of complications is expected to rise proportionally. Surgical complications are associated with significant physiological and psychological morbidity and mortality. While there are generic complications that affect all types of surgery, each specific type of surgery in addition carries its own speciality specific complications. General complications like pain, bleeding, atelectasis, infection and venous thromboembolism are just a few that can complicate the postoperative recovery phase. It cannot be over emphasized that the key to managing surgical complications is preventing them from manifesting in the first place. Preoperative assessment clinics and the implementation of the WHO checklist have allowed the identification and optimization of risk factors. This article explores the prevention and management of common surgical complications which a junior surgical trainee is likely to face.

Objective To assess the initial clinical experience with a novel endograft system (NEXUS Aortic Arch Stent Graft System) designed to treat aortic arch pathologies and address the morphology and hemodynamic challenges of the aortic arch. Summary background data The aortic arch remains the most challenging part of the aorta for both open and endovascular repair. Transcatheter aortic arch repair has the potential to significantly reduce surgical risks. Methods Patients underwent transcatheter aortic arch repair with a single branch, two stent graft system, implanted over a through-and-through guidewire from the brachiocephalic trunk, to the descending aorta with an ascending aorta stent graft. The ascending aorta stent graft is deployed into a designated docking sleeve to connect the two stent grafts and isolate the aortic arch pathology. Proximal landing zone in all cases was in Zone 0. Anatomical inclusion criteria included adequate landing zone in the ascending aorta, brachiocephalic trunk and descending thoracic aorta. Preparatory debranching procedure was performed in all patients with carotid - carotid crossover bypass and left carotid to left subclavian bypass, or parallel graft from descending aorta to left subclavian artery. Safety and performance were evaluated through one year. Survival analysis used the Kaplan-Meier method. Results Twenty-eight patients, 79% males, with a mean age of 72.2 ± 6.2 years were treated with 100% procedural success. Isolated aortic arch aneurysm was the principle pathology in 17 (60.7%) of patients while chronic aortic dissection was the principle pathology in 6 (21.4%) of patients. The remaining 5(17.8%) had combined or other pathologies. At one month, the vascular pathology was excluded in 25 of 26 alive patients (96.1%). The 30 days mortality rate was 7.1%, stroke rate was 3.6% (all non-disabling) and combined mortality/stroke rate was 10.7%. One year mortality was 10.7%, without device or aneurysm related death. Two patients (7.1%) reported stroke or transient ischemic attack at one year that recovered completely. One year combined mortality/stroke rate was 17.8%. There were three patients (10.7%) that had device related unplanned reinterventions through one year. Conclusions The NEXUS Aortic Arch Stent Graft System, a novel single branch, two stent graft system used for endovascular aortic arch repair that requires landing in the ascending aorta, demonstrates a high success rate with excellent one year safety and performance.

One of the commonest symptomatology in gynecological outpatient clinics is chronic pelvic pain, it accounts for 10% of gynecologist’s general clinics patients. The study aimed to To evaluate the role of laparoscopy in evaluation of CPP, and its correlation with clinical examination and vaginal ultrasound examination. The present prospective study was done in the Department of Obstetrics and Gynecology Salah Al-Deen general hospital in Tikrit city from 1stApril- 31st August 2020. The study sample consists of 30 patients with chronic pelvic pain, according to the ACOG criteria, with a convenient sampling method. The data collection done through: a designed closed and open-ended questionnaire, physical examination, transvaginal ultrasound & laparoscopic examination for the 30 patients for evaluation of chronic pelvic pain. By laparoscopic examination (90%) of patients had positive findings, pelvic examination identified (89%) of them correctly. Those with negative findings in laparoscopy was (10%) of patient, (33.3%) of them were diagnosed as negative by pelvic examination, there were miss diagnosis in (67%) of the negative patient and (11.1%) of positive diagnosed patient, this was a statically significant relation. Sensitivity of TVS was 85%, versus 89% for the pelvic examination. Specificity for TVS, and pelvic examination was (100%), (33%) respectively. Accuracy of the test for TVS, and pelvic examination was (87%), (83%) respectively. Exploratory laparoscopy provides a definitive diagnosis in 90% of women complaining of unexplained CPP. The surgical treatment of these lesions improves painful symptomatology in 70% of women .

MDS matrices play an important role in the design of block ciphers, and constructing MDS matrices with fewer xor gates is of significant interest for lightweight ciphers. For this topic, Duval and Leurent proposed an approach to construct MDS matrices by using three linear operations in ToSC 2018. Taking words as elements, they found \begin{document}$ 16\times16 $\end{document} and \begin{document}$ 32\times 32 $\end{document} MDS matrices over \begin{document}$ \mathbb{F}_2 $\end{document} with only \begin{document}$ 35 $\end{document} xor gates and \begin{document}$ 67 $\end{document} xor gates respectively, which are also the best known implementations up to now. Based on the same observation as their work, we consider three linear operations as three kinds of elementary linear operations of matrices, and obtain more MDS matrices with \begin{document}$ 35 $\end{document} and \begin{document}$ 67 $\end{document} xor gates. In addition, some \begin{document}$ 16\times16 $\end{document} or \begin{document}$ 32\times32 $\end{document} involutory MDS matrices with only \begin{document}$ 36 $\end{document} or \begin{document}$ 72 $\end{document} xor gates over \begin{document}$ \mathbb{F}_2 $\end{document} are also proposed, which are better than previous results. Moreover, our method can be extended to general linear groups, and we prove that the lower bound of the sequential xor count based on words for \begin{document}$ 4 \times 4 $\end{document} MDS matrix over general linear groups is \begin{document}$ 8n+2 $\end{document} .

Background The success of Mohs micrographic surgery depends on the surgeon's ability to correctly interpret intraoperative frozen sections. Objective This retrospective study analyzed the rate of concordance between Mohs surgeons and dermatopathologists in reading slides from Mohs surgery cases. Methods A dermatopathologist reviewed all the frozen sections and the corresponding Mohs map for every 30 th Mohs case at a practice employing 6 different Mohs surgeons from 2001-2017. Cases in which the dermatopathologist and the Mohs surgeon disagreed on the interpretation were noted. Results The concordance rate between Mohs surgeons and dermatopathologists was 99.79%. The three discordant cases included one case each of squamous cell carcinoma, superficial basal cell carcinoma, and hypertrophic squamous cell carcinoma in situ. Limitations This analysis is limited to fellowship-trained Mohs surgeons and therefore may not be applicable to all physicians who perform Mohs. Conclusions Fellowship-trained Mohs surgeons show very high concordance with board-certified dermatopathologists in the accurate and precise interpretation of histology slides in the setting of Mohs micrographic surgery.

Data on predictors and time to relapse in patients with psoriasis who discontinue therapy in a real-world setting are scarce.To investigate predictors of relapse after withdrawal of ustekinumab in patients with psoriasis.This study screened 500 patients with psoriasis who received ustekinumab (669 treatment episodes) between 2011 and 2018. Overall, 202 patients (accounting for 304 treatment episodes) who had responded to therapy and were withdrawn from ustekinumab treatment were included.The cumulative probabilities of being relapse-free at 6, 12, 18, 24, and 36 months after withdrawal from ustekinumab treatment were 49.3%, 12.6%, 5.3%, 4.7%, and 1.6%, respectively. Multivariate regression analyses with a generalized estimating equation showed that after adjustments, biologic-naive status, maximum improvement in Psoriasis Area and Severity Index during ustekinumab treatment, time to achieve a 50% improvement in baseline Psoriasis Area and Severity Index score after initiation of ustekinumab, family history of psoriasis, chronic kidney disease, and immunosuppressant use while not taking ustekinumab were significant predictors of time to relapse following discontinuation of ustekinumab.Nonrandomized allocation of duration of treatment and follow-up.Given the high rates of relapse, withdrawal of ustekinumab from patients with well-controlled psoriasis cannot be recommended.

Resumen Introduccion y objetivos Los nodulos tiroideos requieren con frecuencia evaluacion mediante ecografia y puncion aspiracion con aguja fina (PAAF). No obstante, la PAAF no permite la diferenciacion entre adenoma y carcinoma folicular en lesiones de tipo IV segun la clasificacion de Bethesda. Esto provoca numerosas intervenciones quirurgicas innecesarias porque no es posible garantizar el caracter benigno de las lesiones, ni siquiera cuando la mayoria de las muestras corresponden a adenomas o incluso a otras lesiones benignas. El objetivo de este estudio es establecer si hay caracteristicas ecograficas que nos ayudarian a pronosticar el riesgo de malignidad de los nodulos con un diagnostico anatomopatologico de neoplasia folicular para conseguir un abordaje mas conservador de los nodulos sin sospecha de malignidad. Material y metodos Estudiamos 61 nodulos en 61 pacientes (51 mujeres y 10 varones) que se habian sometido a intervencion quirurgica de la glandula tiroides y tenian resultados histopatologicos de adenoma o carcinoma folicular. Se analizaron diversas caracteristicas ecograficas de los nodulos (composicion, ecogenicidad, borde, estado de calcificacion, presencia de halo y sospecha general de malignidad segun el observador) y se establecio su correlacion con el analisis histopatologico. Resultados Observamos una relacion estadisticamente significativa entre el carcinoma folicular y la presencia de calcificaciones, bordes mal definidos y la sospecha o impresion general del observador (definida por sospecha clara de signos ecograficos de malignidad, como calcificacion, borde mal definido y un nodulo solido marcadamente hipoecoico; y signos ecograficos de benignidad, como composicion ecogenica predominantemente quistica y presencia de halo hipoecogenico perinodular). Sin embargo, todas estas caracteristicas han mostrado una sensibilidad baja en el estudio que nos ocupa (30%, 30% y 50%, respectivamente). En cambio, la ausencia del signo de halo ha demostrado una sensibilidad del 100% y un valor predictivo negativo del 100% en nuestro estudio. Conclusiones La presencia de calcificaciones, los bordes mal definidos y la impresion o sospecha general de malignidad se asocian con un riesgo mayor de carcinoma folicular en nodulos tiroideos de tipo IV segun la clasificacion de Bethesda, pero su ausencia no permite pronosticar el caracter benigno de estos nodulos. En cambio, cuando se observa una lesion con signo de halo, deberia considerarse una neoplasia folicular benigna.

Bladder cancer is an aggressive and lethal disease. Even when presenting as localized muscle-invasive disease, the 5-year survival rate is about 70%, and the recurrence rate after radical cystectomy is approximately 50%. Neoadjuvant chemotherapy (NAC) has the potential to downstage the primary tumor and treat micrometastases, leading to a decrease in recurrence rates and an increase in cure rates. There is level 1 evidence in favor of neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy. However, data from clinical trials evaluating NAC for patients undergoing bladder-sparing treatments are less robust, so this strategy remains controversial. The response to NAC is prognostic and patients with favorable pathological response have better overall survival. Strategies to select patients based on molecular biomarkers have the potential to guide treatment decisions and even de-intensify treatment, avoiding local treatment for those with complete responses to systemic therapy. This review outlines the current literature on the use of NAC in the context of bladder preservation for muscle-invasive bladder cancer, highlights neoadjuvant studies in patients ineligible for cisplatin-based NAC, and discusses novel bladder-preservation strategies, including multimodality combinations and biomarker-driven studies of definitive chemotherapy.

Non-muscle-invasive bladder cancer is one of the most common malignancies. Patients with intermediate-risk or high-risk disease can be treated with intravesical Bacillus Calmette-Guerin, a vaccine against tuberculosis. However, many of these patients will experience tumor recurrence, despite appropriate treatment. 1 The standard of care in these patients is radical cystectomy (RC) with urinary diversion. 2 Patients diagnosed with muscle-invasive bladder cancer (MIBC) have traditionally faced 2 main treatment options: RC and urinary diversion, as in Bacillus Calmette-Guerin-unresponsive Non-muscle-invasive bladder cancer, or alternatively, trimodal therapy comprising maximal transurethral resection of bladder tumor plus chemoradiation. 3 For patients with MIBC and clinical (c)T2-T4a, neoadjuvant chemotherapy (NAC) preceding RC is supported by Level 1 evidence with a modest 5-year overall survival benefit of 5% with cisplatin-based regimens. 4-9 A number of factors preclude MIBC patients from standard treatment options. For example, patients with serious comorbidities might be unable to tolerate general anesthesia, while others might be unwilling to adapt to the lifestyle changes after RC. 10-12 Likewise, patients with extensive carcinoma in situ or poor bladder function might not be optimal candidates for trimodal therapy or be prepared for the ongoing risk that salvage RC might be ultimately required. Reasons for the underuse of NAC range from the fear of delaying potentially curative surgery in nonresponders to patient ineligibility to cisplatin-based NAC. 13,14 Despite best efforts, in both surgical and bladder-sparing approaches, the 5-year overall survival in treated patients with MIBC is only 35% to 50%. 3,15 Strategies to improve overall prognosis as well as to reduce the indications of RC are desperately needed. Trial results have demonstrated the unprecedented ability of immune-checkpoint inhibitors to induce durable remissions in some patients with metastatic urothelial carcinoma. 16-20 Furthermore, immune-checkpoint inhibitors have shown to be better tolerated than traditional chemotherapy. 16 These successful results have spearheaded the research on these agents in earlier curative settings, with the shared goal of improving overall outcomes, and potentially avoid surgery in patients who show complete response (pT0). Strategies to enhance the immune response by combining immunotherapy with immune sensitizers such as chemotherapy, immunotherapy, targeted therapy or radiation are on the rise.

International Dermatology Outcome Measures and the American Academy of Dermatology recently agreed on a physician-reported global severity measure to demonstrate quality of care in inflammatory dermatoses.Because patient-reported outcome measures are also important, we aimed to achieve consensus on 1 of these measures for clinical practice.Patients and providers participated in a consensus-building study involving a modified-Delphi technique. Voting was focused on identifying a minimal set of assessments for clinical practice, patient global assessments (PtGAs), Skindex instruments, and final instrument selection for quality improvement.Among 53 stakeholders,70% agreed that identification of patient goals, assessment of treatment harm, and assessment of the adequacy of treatment response were the minimal assessments needed for clinical practice. The most preferred PtGA was a 5-point PtGA (scale 0-4; 0 = clear, 4 = severe) having an optional check-box for worst ever. A new metric to assess change since treatment initiation, which we called a trajectory measure, was proposed. Stakeholders preferred Skindex instruments over PtGAs and a trajectory measure for clinical practice.A small number of patients and caregivers were involved and a consensus was not reached on all items.PtGAs as standalone measures do not adequately capture the patient's assessment of disease severity or the effect of care. The combination of a PtGA with a Skindex instrument or another measure of health-related quality of life might provide a more comprehensive evaluation of patients in clinical practice.

Background: Hyaluronic acid fillers are known for a reliable safety profile, but complications do occur, even serious vascular adverse events. Objective: To improve the treatment outcome after a vascular adverse event with use of hyaluronic acid filler treatments.Methods: Duplex ultrasonography is used to detect the hyaluronic acid filler causing the intra-arterial obstruction. Results: If treated in time, 1 single treatment of ultrasonographically guided injections of hyaluronidase into the filler deposit will prevent skin necrosis. Conclusion: Because the use of duplex ultrasonography adds extra essential information, its use may become an integral part of the prevention and treatment of injection adverse events.

Resumen Antecedentes y objetivo El manejo actual de la diverticulitis aguda de colon izquierdo requiere pruebas con alto valor pronostico. Los objetivos del estudio son analizar la utilidad de la ecografia como metodo diagnostico inicial y evaluar la validez de las clasificaciones actuales de gravedad de dicha enfermedad. Pacientes Estudio observacional retrospectivo de pacientes con diverticulitis aguda de colon izquierdo. Se solicito ecografia o tomografia computarizada (TC) siguiendo un algoritmo clinico. Tras los hallazgos de imagen, se clasifico la enfermedad como leve, localmente complicada y complicada. Se evaluaron la eficacia de la ecografia como herramienta diagnostica inicial y las razones por las que se realizo una TC como tecnica inicial. Se compararon los hallazgos con las clasificaciones de diverticulitis publicadas. Resultados De 311 pacientes con diverticulitis aguda, se seleccionaron 183 con diverticulitis aguda de colon izquierdo, que fueron clasificadas por imagen como leves (104), localmente complicadas (60) y complicadas (19). En 98 pacientes, el diagnostico se realizo por ecografia, en 77 por TC y en 8 mediante ambas. Las principales razones de utilizacion inicial de TC fueron falta de experiencia del radiologo en ecografia abdominal y falta de disponibilidad de un radiologo de guardia. A 6 pacientes diagnosticados por ecografia se les realizo una nueva evaluacion por TC, pero solo en 3 cambio la clasificacion. Ninguna de las clasificaciones publicadas recoge todos los hallazgos en imagen. Conclusiones La ecografia deberia ser la primera tecnica a utilizar para el diagnostico de diverticulitis aguda de colon izquierdo. Para establecer el pronostico de la enfermedad, son utiles diversos parametros analiticos y hallazgos de imagen. Para una apropiada toma de decision terapeutica se necesitarian nuevas clasificaciones de gravedad.

Radical cystectomy with bilateral pelvic lymphadenectomy and trimodality bladder-sparing therapy or TMT, are both curative options for patients with nonmetastatic muscle invasive bladder cancer. Patients should be afforded the opportunity for a multidisciplinary evaluation with equipoise in discussing these options for eligible patients. We discuss the barriers to broader acceptance and utilization of TMT and encourage support of clinical trials of TMT.

ZusammenfassungTabakrauchen ist die wichtigste vermeidbare Krebsursache in Deutschland. Je mehr und je länger jemand raucht, desto stärker steigt sein Krebsrisiko. Wird Tabakrauch kombiniert mit Alkohol, vervielfacht sich das Krebsrisiko. Bis zu 30 % der Krebstodesfälle können auf das Rauchen zurückgeführt werden. 23,3 % der 18- bis 64-jährigen Bevölkerung rauchen und weitere 11 % sind hierzulande regelmäßig einer Passivrauch­belastung ausgesetzt. Zu den Tabakrauch-assoziierten Malignomen zählen Karzinome der Mundhöhle, der Nase, der Nebenhöhlen, des Pharynx, des Larynx, der Lunge, des Ösophagus, des Magens, des Pankreas, der Leber, der Gallenwege, des Dickdarms, der Nieren, der Ureteren, der Harnblase, der Zervix und der Eierstöcke sowie Leukämien. Bei stattgehabter Tabakexposition soll den Betroffenen frühzeitig zu etablierten Krebsfrüh­erkennungsmaßnahmen geraten werden. Rauchern soll eine professionelle Tabakentwöhnung angeboten werden. Das tabakbedingte Krebsrisiko wird durch den Rauchstopp effektiv und zeitabhängig gesenkt.

Background Despite high utilization of complementary and alternative medicine (CAM) for alopecia areata (AA), efficacy and safety remain unclear. Objective To identify all CAM therapies studied for treatment of AA. Outcomes of interest included disease course and psychological well-being. Methods PubMed and Embase were searched to identify English articles containing original data investigating CAM in human subjects with AA from 1950-2018. Quality was assessed with Oxford Centre for Evidence Based Medicine criteria. Results Of 1,015 initial citations, 16 articles met inclusion criteria: 5 randomized controlled trials, 5 prospective controlled cohorts, 4 prospective non-controlled cohorts, 1 retrospective cohort, and 1 case series. CAM therapies with best evidence and efficacy for hair growth in AA include essential oil aromatherapy, topical garlic, and oral glucosides of peony with compound glycyrrhizin. Hypnosis and mindfulness psychotherapy represent low quality evidence for improvement of psychological and quality of life outcomes. Adverse events were rare and mild for all therapies evaluated. Limitations Inconsistent or poorly reported study methodology and non-standardized outcomes limit the conclusions that can be made from these studies. Conclusions This work serves to inform physician management of patients with AA seeking CAM, while encouraging further investigation into these therapies to address some of the therapeutic challenges of AA.