Hyaluronic acid injections in post-enucleation or evisceration socket syndrome: a case series

Background: One of the primary goals of enucleation and evisceration surgery is the restoration of an adequate orbital volume through the use of appropriately sized alloplastic or autogenous tissues. In patients inadequately treated, post-enucleation or evisceration socket syndrome occurs. Fillers are an ideal alternative for eyelid and eyebrow arcade volume enhancement since their injection is easily performed in an outpatient setting avoiding several complications. The aim of this study is to report the use of hyaluronic acid (HA) fillers to treat volume deficits of the upper and lower eyelids, projecting the brow arcade and reducing the asymmetry. Methods: Thirteen patients (2 male, 11 female, mean age 32.7 years) were treated from June 2012 to May 2020. Non-surgical treatment by HA filler injection for aesthetic rehabilitation of deep superior sulcus, inferior tear trough deformity, and scleral show was performed. Results: No complications as orbital-ache and/or vasovagal response were reported during the injections. Minor complications such as light swelling at the site of injection, self-resolved within 2 days, were recorded. Stable results were observed at follow-ups. In two cases, two successive treatments were required at 3 and 6 years from the first injection. Conclusions: Hyaluronic acid fillers offer a versatile and safe method for replacing soft tissue lost from the upper eyelid/brow complex in cases of post-enucleation or evisceration socket syndrome. Level of evidence: Level IV, therapeutic study

Effect of fluvoxamine on plasma risperidone concentrations in patients with schizophrenia

The effect of fluvoxamine on plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was investigated in 11 schizophrenic patients with prevailingly negative or depressive symptoms. Additional fluvoxamine, at the dose of 100 mg/day, was administered for 4 weeks to patients stabilized on risperidone (3–6 mg/day). Mean plasma concentrations of risperidone, 9-OH-risperidone and the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) were not significantly modified following co-administration with fluvoxamine. After 4 weeks, fluvoxamine dosage was increased to 200 mg/day in five patients and then maintained until the end of week 8. At final evaluation, mean plasma levels of risperidone active moiety were not modified in the six patients who were still receiving the initial fluvoxamine dose, while concentrations increased slightly but significantly (by a mean 26% over pretreatment; P < 0.05) in the subgroup of five subjects treated with a final dose of 200 mg/day. Fluvoxamine co-administration with risperidone was well tolerated and no patient developed extrapyramidal side effects. These findings indicate that fluvoxamine at dosages up to 100 mg/day is not associated with clinically significant changes in plasma risperidone concentrations. However, higher doses of fluvoxamine may elevate plasma risperidone levels, presumably as a result of a dose-dependent inhibitory effect of fluvoxamine on CYP2D6-and/or CYP3A4-mediated 9-hydroxylation of risperidone

P569 Clinical correlations of infliximab trough levels (IFX-TL) and antibodies to infliximab (ATI) in inflammatory bowel disease

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Plasma Concentrations of Risperidone and Olanzapine during Coadministration with Oxcarbazepine

Purpose: Oxcarbazepine (OZC) is a secondgeneration antiepileptic drug (AED) that also may be used as a mood stabilizer. Unlike carbamazepine (CBZ), which is an inducer of the cytochrome P-450 isoforms and may accelerate the elimination of several therapeutic agents, OXC seems to have only a modest inducing action. The aim of this investigation was to evaluate the effect of a treatment with OXC on plasma concentrations of the new antipsychotics risperidone and olanzapine. Methods: OXC, at a dosage of 900–1,200 mg/day, was administered for 5 consecutive weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years, with bipolar or schizoaffective disorder. Twelve patients were stabilized on risperidone therapy (2–6 mg/day) and 13 on olanzapine (5–20 mg/day). Steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and olanzapine were measured by high-pressure liquid chromatography (HPLC) before addition of OXC and after 5 weeks from the start of adjunctive treatment. Results:OXC caused only minimal and no significant changes in the mean plasma levels of risperidone (from 5.6±3.6 ng/ml at baseline to 4.8 ± 2.6 ng/ml at week 5), 9-OH-risperidone (from 23.6±7.5 to 24.7±7.4 ng/ml), and olanzapine (from 26.5±5.7 ng/ml at baseline to 27.8 ± 5.1 ng/ml). OXC coadministration with either risperidone or olanzapine was well tolerated. Conclusions: Our findings indicate that OXC does not affect the elimination of risperidone and olanzapine, thus confirming its weak inducing effect on hepatic drug-metabolizing enzymes

Colorectal cancer residual disease at maximal response to EGFR blockade displays a druggable Paneth cell–like phenotype

Blockade of epidermal growth factor receptor (EGFR) causes tumor regression in some patients with metastatic colorectal cancer (mCRC). However, residual disease reservoirs typically remain even after maximal response to therapy, leading to relapse. Using patient-derived xenografts (PDXs), we observed that mCRC cells surviving EGFR inhibition exhibited gene expression patterns similar to those of a quiescent subpopulation of normal intestinal secretory precursors with Paneth cell characteristics. Compared with untreated tumors, these pseudodifferentiated tumor remnants had reduced expression of genes encoding EGFR-activating ligands, enhanced activity of human epidermal growth factor receptor 2 (HER2) and HER3, and persistent signaling along the phosphatidylinositol 3-kinase (PI3K) pathway. Clinically, properties of residual disease cells from the PDX models were detected in lingering tumors of responsive patients and in tumors of individuals who had experienced early recurrence. Mechanistically, residual tumor reprogramming after EGFR neutralization was mediated by inactivation of Yes-associated protein (YAP), a master regulator of intestinal epithelium recovery from injury. In preclinical trials, Pan-HER antibodies minimized residual disease, blunted PI3K signaling, and induced long-term tumor control after treatment discontinuation. We found that tolerance to EGFR inhibition is characterized by inactivation of an intrinsic lineage program that drives both regenerative signaling during intestinal repair and EGFR-dependent tumorigenesis. Thus, our results shed light on CRC lineage plasticity as an adaptive escape mechanism from EGFR-targeted therapy and suggest opportunities to preemptively target residual disease

ANALISIS SISTEM PENGENDALIAN INTERN PENERIMAAN DAN PENGELUARAN KAS PADA PT. ASURANSI BRINGIN SEJAHTERA ARTAMAKMUR CABANG MEDAN

Penelitian ini bertujuan untuk mengetahui sejauh mana sistem pengendalian intern penerimaan dan pengeluaran kas yang dilakukan PT. Asuransi Bringin Sejahtera Artamamakmur Cabang Medan dalam menjalankan kegiatan usahanya guna mencapai tujuan perusahaan. Teori yang digunakan dalam penelitian ini adalah teori Mulyadi. Metode yang digunakan dalam penelitian ini adalah Penelitian Kualitatif, dengan teknik analisis data Deskriptif, yaitu dengan terlebih dahulu mengumpulkan data, mengklasifikasikan serta menafsirkan data sehingga dapat memberikan gambaran yang jelas mengenai masalah yang diteliti. Dalam pengumpulan data menggunakan teknik wawancara dan dokumentasi, dimana data yang diambil merupakan data primer yang berupa bukti catatan atau laporan historis yang telah tersusun dalam arsip yang dipublikasi maupun yang tidak dipublikasikan. Hasil penelitian ini menunjukan bahwa pengendalian intern penerimaan dan pengeluaran kas PT. Asuransi Bringin Sejahtera Artamakmur Cabang Medan belum sepenuhnya memenuhi unsur-unsur pengendalian intern, karena masih adanya beberapa hal yang tidak sesuai dengan teori yang ada. Diantaranya, masih ada perangkapan tugas yang dilakukan bagian kasir dengan bagian akuntansi. Demikian juga dalam hal pembagian tugas, dimana bagian kasir diberi tanggung jawab dalam hal penagihan premi, yang sebaiknya tugas ini bukan dipegang unit tersebut. Praktik-praktik ini ditakutkan akan mengurangi keakuratan pencatatan dan juga akan membuka peluang terjadinya penyelewengan terhadap kas yang mengakibatkan kerugian perusahaan. Hal ini juga akan mengurangi keefektifan dalam praktik kerja bagian kasir, karena terlalu banyak memegang fungsi

Epidermal Growth Factor Receptor (EGFR) mutation analysis, gene expression profiling and EGFR protein expression in primary prostate cancer

<p>Abstract</p> <p>Background</p> <p>Activating mutations of the epidermal growth factor receptor (<it>EGFR</it>) confer sensitivity to the tyrosine kinase inhibitors (TKi), gefitinib and erlotinib. We analysed EGFR expression, EGFR mutation status and gene expression profiles of prostate cancer (PC) to supply a rationale for EGFR targeted therapies in this disease.</p> <p>Methods</p> <p>Mutational analysis of EGFR TK domain (exons from 18 to 21) and immunohistochemistry for EGFR were performed on tumour tissues derived from radical prostatectomy from 100 PC patients. Gene expression profiling using oligo-microarrays was also carried out in 51 of the PC samples.</p> <p>Results</p> <p>EGFR protein overexpression (EGFR_high) was found in 36% of the tumour samples, and mutations were found in 13% of samples. Patients with EGFR_hightumours experienced a significantly increased risk of biochemical relapse (hazard ratio-HR 2.52, p=0.02) compared with patients with tumours expressing low levels of EGFR (EGFR_low). Microarray analysis did not reveal any differences in gene expression between EGFR_highand EGFR_lowtumours. Conversely, in EGFR_hightumours, we were able to identify a 79 gene signature distinguishing mutated from non-mutated tumours. Additionally, 29 genes were found to be differentially expressed between mutated/EGFR_high(n=3) and mutated/EGFR_lowtumours (n=5). Four of the down-regulated genes, U19/EAF2, ABCC4, KLK3 and ANXA3 and one of the up-regulated genes, FOXC1, are involved in PC progression.</p> <p>Conclusions</p> <p>Based on our findings, we hypothesize that accurate definition of the EGFR status could improve prognostic stratification and we suggest a possible role for EGFR-directed therapies in PC patients. Having been generated in a relatively small sample of patients, our results warrant confirmation in larger series.</p

Self-medication of migraine and tension-type headache: summary of the evidence-based recommendations of the Deutsche Migräne und Kopfschmerzgesellschaft (DMKG), the Deutsche Gesellschaft für Neurologie (DGN), the Österreichische Kopfschmerzgesellschaft (ÖKSG) and the Schweizerische Kopfwehgesellschaft (SKG)

The current evidence-based guideline on self-medication in migraine and tension-type headache of the German, Austrian and Swiss headache societies and the German Society of Neurology is addressed to physicians engaged in primary care as well as pharmacists and patients. The guideline is especially concerned with the description of the methodology used, the selection process of the literature used and which evidence the recommendations are based upon. The following recommendations about self-medication in migraine attacks can be made: The efficacy of the fixed-dose combination of acetaminophen, acetylsalicylic acid and caffeine and the monotherapies with ibuprofen or naratriptan or acetaminophen or phenazone are scientifically proven and recommended as first-line therapy. None of the substances used in self-medication in migraine prophylaxis can be seen as effective. Concerning the self-medication in tension-type headache, the following therapies can be recommended as first-line therapy: the fixed-dose combination of acetaminophen, acetylsalicylic acid and caffeine as well as the fixed combination of acetaminophen and caffeine as well as the monotherapies with ibuprofen or acetylsalicylic acid or diclofenac. The four scientific societies hope that this guideline will help to improve the treatment of headaches which largely is initiated by the patients themselves without any consultation with their physicians