Social stigmatization in Turkish patients with chronic hepatitis B and C

Background and aimViral hepatitis is the most important cause of chronic hepatitis worldwide. Stigmatization is defined as a feeling of rejection and isolation of patients by society due to illness. There are no studies on chronic viral hepatitis in the literature in English, which has its own religious and socio-cultural structure. In our study, we aimed to investigate the presence of social stigmatism and psychosocial effects on patients with different stages of chronic viral hepatitis B and C.MethodsForty-five patients with chronic hepatitis C and 114 patients with chronic hepatitis B were enrolled in the study. Berger's scale was used for stigmatization, composed of 40 four-point Likert items that have four subscales: personalized stigma, disclosure, negative self-image, and public attitude. Stigma score ranges between one and four. Stigma is accepted as present if the overall score is above two.ResultsOverall the mean stigma scores were 1.97 ± 0.58 and 2.14 ± 0.57 for chronic hepatitis B and C, respectively. There was stigma in 47.4% of the patients with chronic hepatitis B, and 60% of the patients with chronic hepatitis C. Being male was the risk factor on overall stigma, disclosure and public attitude in chronic hepatitis C. Living in an urban setting was the risk factor on negative self-image in chronic hepatitis C and on personalized stigma and disclosure in chronic hepatitis B.ConclusionsTo the best of our knowledge, this is the first study that provides qualitative information about chronic hepatitis-related stigma. Stigmatization is a major problem in Turkey and worldwide. We believe that increasing the knowledge of the patients and society by teaching about the transmission routes of the disease and focusing on vaccination studies will prevent stigmatization.     

Structural,Functional and Autonomic Changes in the Cardiovascular System in Growth Hormone Deficient Patients

Background: Growth hormone deficiency (GHD) is known to cause higher rates of cardiovascular mortality. The purpose of the study was to analyze the structural and functional changes in the heart and investigate their relation to autonomic function as assessed with heart rate variability (HRV). Methods: Eleven untreated GHD patients (mean age 50.4 ± 10.7 years, M/F: 3/8) and 15 age‐ and sex‐matched healthy persons (mean age 45.3 ± 10.4 years, M/F: 5/10) were compared. Both groups were examined with echocardiography, HRV, and exercise testing and findings were analyzed. Results: The groups were similar in height, weight, body mass index, body surface area, systolic and diastolic blood pressure, heart rate. The GHD patients had lower exercise duration and metabolic equivalent (MET) compared to controls (7.94 ± 1.26 vs. 9.8 ± 1.9 min, P < 0.001, for MET 8.85 ± 0.86 vs. 10.7 ± 2.23, P = 0.03). On echocardiography, GHD patients had lower interventricular septum diastolic diameter (9 ± 0.89 vs. 10.7 ± 0.88 mm, P < 0.001) and posterior wall thickness (8.4 ± 0.93 vs. 9.8 ± 0.91 mm, P = 0.002), and lower left ventricle mass index (90.9 ± 20 vs. 112 ± 8 g/m², P = 0.01). Left ventricular ejection fraction was lower in the GHD patients (57.4 ± 5.12% vs. 65.5 ± 4.1%, P < 0.001). Time and frequency domain heart rate variability parameters, SDNN, SDANN, VLF, LF ve LF/HF were lower in GHD patients compared to controls. There was a significant correlation between left ventricle diastolic diameter and LF (r = 0.62, P = 0.02). Conclusion: GHD seemed to cause decreased left ventricle mass and decreases in the sympathetic components of HRV that may have a bearing on the increased cardiovascular risk seen in these patients.     

A rare etiology of acute abdominal syndrome in adults: Gastric volvulus – Cases series

INTRODUCTION

Gastric volvulus is a rare surgical emergency with a high mortality rate that requires urgent surgical management.

PRESENTATION OF CASE

A 19-year-old male and 51-year-old female patient underwent emergency surgery with a prediagnosis of acute abdomen syndrome, and a 60-year-old female patient underwent elective surgery due to diaphragmatic hernia. Abdominal exploration revealed gastric volvulus together with perforation in received emergency surgery patients, and a mesenteroaxial gastric volvulus due to diaphragmatic defect in third patient.

DISCUSSION

Gastric volvulus is classified into four subgroups depending on the mechanism of development, and organoaxial form is the most common type of gastric volvulus. The most challenging step in diagnosing gastric volvulus is the consideration of this diagnosis.

CONCLUSION

Preoperative diagnosis is often difficult, and its management involves surgical correction of the pathology followed by institution of resuscitative treatment.     

Urinary calcium excretion in Swedish children

Urinary calcium excretion was measured in an unselected population of 153 healthy Swedish children aged 2–18 years. Urine was collected after an ordinary meal. Urinary calcium excretion was measured as the calcium/creatinine concentration ratio (UCa/Cr) and expressed in mmol/1 per mmol/1. UCa/Cr was 0.44 ± 0.379 (mean ±SD). As the UCa/Cr in this childhood population was not distributed in a normal manner, the results are more correctly presented as the 50th (0.33) and 97th (1.5) centiles. There was a weak but significant correlation between UCa/Cr and age, with higher values in the lower age groups. There was no correlation between UCa/Cr and the anamnestic intake of cow's milk. Repeated samples from some children showed a coefficient of variation between days of 30–40%. The upper limits of normal UCa/Cr (97th centile = 1.5; +2 SD = 1.2) in this investigation were higher than what is considered normal by others. In spite of this, none of the children had a history of renal stone disease or any other symptoms of hypercalciuria. Renal stone disease is thought to be rare in Swedish children although the real incidence is not known. The diagnosis of hypercalciuria should be based on repeated samples from an individual with symptoms and related to age-related reference values from the same population group.     

Prognostic Significance of Depth of Invasion in Cancer of the Larynx

To determine the prognostic significance of depth of invasion in laryngeal cancer, the depth of invasion of tumor was measured with an ocular micrometer on the laryngectomy specimens of 94 surgically treated patients with T1, T2, and T3 laryngeal cancer and was expressed in millimeters. There was a significant negative correlation between the depth of invasion and disease-free survival. The tumors with no clinical involvement of regional lymph nodes in neck (N0 neck) had significantly less depth of invasion than those with involvement (N+ neck). The tumors with pathologically confirmed cervical lymph node metastasis had significantly more depth of invasion than those without metastasis. For tumors with a depth of invasion equal to or greater than 3.25 mm, the rate of cervical metastasis in this study has always been significantly higher than for those with a depth of invasion less than 3.25 mm (P < .05). The mean depths of invasion for cases with and without recurrence were not significantly different. According to the multivariate analysis, depth of invasion (P = .047) and patient age (P = .113) significantly affected the disease-free survival independently. The depth of invasion did not significantly affect the recurrence and the interval between surgery and the development of recurrence (P > .15). The depth of invasion should be measured in every laryngectomy specimen. The depth of invasion influences the cervical metastasis and disease-free survival significantly but does not affect the recurrence rate. The depth of invasion plays an independent role in determining the disease-free survival.     

Carcinosarcoma of the ovary compared to ovarian high-grade serous carcinoma: impact of optimal cytoreduction and standard adjuvant treatment

Objective

The purpose of this retrospective study was to compare the prognoses of women with ovarian carcinosarcoma (OCS) who had optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy to those of women with ovarian high-grade serous carcinoma (HGSC) treated in the same manner.

Methods

A multicenter, retrospective department database review was performed to identify patients with OCS at eight gynecologic oncology centers in Turkey. A total of 54 women with OCS who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy between 1999 and 2017 were included in this case–control study. Each case was matched to two women with ovarian HGSC who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy. The Kaplan–Meier method was used to generate survival data. Factors predictive of outcome were analysed using Cox proportional hazards models.

Results

Median disease-free survival (DFS) was 29 months [95% confidence interval (CI) 0–59, standard error (SE) 15.35] versus 27 months (95% CI 22.6–31.3, SE 2.22; p = 0.765) and median overall survival (OS) was 62 versus 82 months (p = 0.53) for cases and controls, respectively. For the entire cohort, the presence of ascites [hazard ratio (HR) 2.32; 95% CI 1.02–5.25, p = 0.04] and platinum resistance [HR 5.05; 95% CI 2.32–11, p < 0.001] were found to be independent risk factors for decreased OS.

Conclusion

DFS and OS rates of patients with OCS and HGSC seem to be similar whenever optimal cytoreduction is achieved and followed by platinum plus taxane combination chemotherapy.

     

Phosphoproteomic characterization of DNA damage response in melanoma cells following MEK/PI3K dual inhibition

Targeted therapeutics that block signal transduction through the RAS–RAF–MEK and PI3K–AKT–mTOR pathways offer significant promise for the treatment of human malignancies. Dual inhibition of MAP/ERK kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) with the potent and selective small-molecule inhibitors GDC-0973 and GDC-0941 has been shown to trigger tumor cell death in preclinical models. Here we have used phosphomotif antibodies and mass spectrometry (MS) to investigate the effects of MEK/PI3K dual inhibition during the period immediately preceding cell death. Upon treatment, melanoma cell lines responded by dramatically increasing phosphorylation on proteins containing a canonical DNA damage-response (DDR) motif, as defined by a phosphorylated serine or threonine residue adjacent to glutamine, [s/t]Q. In total, >2,000 [s/t]Q phosphorylation sites on >850 proteins were identified by LC-MS/MS, including an extensive network of DDR proteins. Linear mixed-effects modeling revealed 101 proteins in which [s/t]Q phosphorylation was altered significantly in response to GDC-0973/GDC-0941. Among the most dramatic changes, we observed rapid and sustained phosphorylation of sites within the ABCDE cluster of DNA-dependent protein kinase. Preincubation of cells with the inhibitors of the DDR kinases DNA-dependent protein kinase or ataxia-telangiectasia mutated enhanced GDC-0973/GDC-0941–mediated cell death. Network analysis revealed specific enrichment of proteins involved in RNA metabolism along with canonical DDR proteins and suggested a prominent role for this pathway in the response to MEK/PI3K dual inhibition.Dysregulation of the RAS–RAF–MAP/MEK and PI3K–AKT–mTOR pathways represents a common theme in human cancer. The importance of these interconnected pathways is highlighted by the frequency of mutational activation of pathway members including RAS, RAF, and PI3K, as well as inactivation of the inhibitory phosphatase and tensin homolog (PTEN) (1, 2). Targeted therapies that block signaling through the RAS–RAF–MEK pathway, including specific inhibitors of oncogenic forms of BRAF (e.g., BRAF-V600E, which is observed in ∼50% of melanomas) and of the downstream effector MEK have shown clinical efficacy in melanoma and other tumor types (3, 4). Likewise, suppression of cell-survival signaling through inhibition of PI3K has been shown to kill cancer cells (5, 6). Although inhibition of either pathway individually can elicit measureable responses, feedback through signal-transduction networks often limits the effectiveness of single-agent therapies. Mounting evidence suggests that dual inhibition of the RAS–RAF–MEK and PI3K–AKT–mTOR pathways will demonstrate improved efficacy over single-agent therapies.At the heart of the RAS–RAF–MEK and PI3K–AKT–mTOR pathways is a web of phosphorelay networks in which individual phosphorylation sites serve as nodes. Many key nodes reside on protein kinases, where phosphorylation individually and in aggregate modulates the amplitude and specificity of downstream signaling. Our understanding of these networks has been shaped by studies using phosphospecific antibodies against these individual, site-specific phosphorylation events including ERK1/2 at Thr202/Tyr204 (7, 8) and AKT at Thr308 (9, 10). Although this strategy has proven successful, the generation of sensitive phosphospecific reagents capable of reading out signal unambiguously remains a challenge. Likewise, multiply phosphorylated sequences or those occurring adjacent to other posttranslational modifications can confound data interpretation. A key limitation is that phosphospecific antibodies are intended to interrogate only a single node in a signal-transduction network, so that even when multiplexed they provide only a narrow portal through which to view the dynamic system.Mass spectrometry (MS) proteomics provides a platform to dissect signaling networks in breadth and depth. Although theoretically the phosphorylated peptides can be profiled directly from digested cell lysates, interrogating signal-transduction networks requires enrichment of modified peptides from the cellular milieu. One approach involves immunoaffinity enrichment (IAE) with antibodies recognizing classes of phosphopeptides, such as phosphotyrosine (11). IAE methods also have been reported for assaying phosphorylation in the AKT (12) and DNA damage-response (DDR) signaling networks (13, 14), using antibodies that recognize phosphorylation within a local sequence context. For substrates of AKT family kinases, phosphorylation occurs within an RXRXX[s/t] sequence, where X represents any amino acid and [s/t] refers to the phosphorylated serine or threonine (12). For substrates of ataxia-telangiectasia mutated (ATM) and other DDR kinases, phosphorylation occurs on serine or threonine adjacent to glutamine, [s/t]Q (15). In contrast to phosphospecific antibodies directed against a single sequence, motif-specific antibodies recognize a degenerate motif and permit enrichment of an array of peptides. Likewise, these reagents provide a readout for screening conditions by immunoblot before phosphopeptide enrichment and LC-MS/MS.In the current study, we noticed that MEK/PI3K dual inhibition in melanoma lines resulted in a marked DDR. Using motif-directed IAE and MS proteomics, we investigated the signaling elicited by small-molecule inhibitors of MEK and PI3K currently in clinical development to establish a molecular understanding of this response.     

c-myc and bcl-2 Expression in supraglottic squamous cell carcinoma of the larynx.

OBJECTIVES: To evaluate the expression and prognostic significance of c-myc and bcl-2 oncogenes in squamous cell carcinoma (SCC) of the supraglottic larynx.Study design A retrospective cohort study of 61 patients who underwent surgery for SCC of the supraglottic larynx. Gender, age, TNM status, operative procedure, recurrences, and disease-free survival periods were recorded. METHODS: Hematoxylin and eosin-stained sections were reexamined for grade, invasion of tumor margins, lymphovascular invasion, lymphocyte infiltration, and perineural invasion. Immunohistochemical detection of c-myc and bcl-2 oncogenes was performed using monoclonal antibodies. RESULTS: No correlation was observed between either c-myc or bcl-2 and the clinical and histopathologic parameters. Survival analysis revealed no correlation of either c-myc (P = 0.88) or bcl-2 (P = 0.85) with the disease-free survival. c-myc expression was found to be significantly higher in bcl-2-positive patients (P = 0.001). CONCLUSION: Neither c-myc nor bcl-2 had shown to be prognostic factor for laryngeal carcinoma in this present study. Correlation between c-myc and bcl-2 supports the experimental observations of cooperative action between these two genes in tumorigenesis.     

SHORT-TERM EFFECT OF LATANOPOST ON INTRAOCULAR PRESSURE AND OCU-LAR CIRCULATION IN OCULAR HYPER-TENSION

Purpose: To determine the stort-term effects of latano-prost (Xalatan) on the retrobulbar circulation and intraocular pressure (IOP) in ocular hypertension. Materials and Methods: Forty-six eyes of 23 consecutive ocular hypertension patients older than 20 years. All patients had IOP greater than 22 mmHg. One eye of each patient was randomly selected to take