A New Clock is Running for Multiple Myeloma: Circadian Clock Protein-Period 3 (PER-3) Polymorphism.

Circadian Clock Protein PERIOD 3 (PER-3) is situated on chromosome 1p36.23 and has a polymorphic domain that expresses 4 or 5 copies of the 54-bp tandem repeat sequence. PER-3 gene polymorphisms play a role in the dysregulation of the immune system. This study intended to investigate the distributions and clinical effectiveness of the PER-3 gene polymorphism in multiple myeloma (MM) patients. One hundred fifty patients diagnosed between January 2007-2009 and 100 healthy individuals were included in this study. All patients were suitable for autologous stem cell transplantation (ASCT) at first evaluation, and after 4 courses of VCD at least partial remission, ASCT was carried out. Later, LD was used as maintenance. Genotypes of PER-3 gene of patients and healthy controls were statistically compared before treatment. In addition, these genotypes' effects on overall and progression free survival (OS and PFS) were investigated. Median PFS in the 5R/5R genotype was found to be significantly longer, albeit low, at 86% (p = 0.046). In the statistical analysis performed between the 4R/4R genotype and others, the PFS of patients with 4R/4R was found to be significantly shorter at 40.4 months (p = 0.026). Patients with the 4R/4R genotype would have a risk of 2.049 times of a shorter PFS (p=0.009). With this first study investigating the effect of a circadian gene in MM, the net effect of PER-3 gene polymorphism on PFS was revealed, and it will be a guide for future studies.

Effects of COVID-19 Pandemic on the Treatment of Pancreatic Cancer: A Perspective from Central Europe.

BACKGROUND: This survey aimed to register changes determined by the COVID-19 pandemic on pancreatic surgery in a specific geographic area (Germany, Austria, and Switzerland) to evaluate the impact of the pandemic and obtain interesting cues for the future. METHODS: An online survey was designed using Google Forms focusing on the local impact of the pandemic on pancreatic surgery. The survey was conducted at 2 different time points, during and after the lockdown. RESULTS: Twenty-five respondents (25/56) completed the survey. Many aspects of oncological care have been affected with restrictions and delays: staging, tumor board, treatment selection, postoperative course, adjuvant treatments, outpatient care, and follow-up. Overall, 60% of respondents have prioritized pancreatic cancer patients according to stage, age, and comorbidities, and 40% opted not to operate high-risk patients. However, for 96% of participants, the standards of care were guaranteed. DISCUSSION/CONCLUSIONS: The first wave of the COVID-19 pandemic had an important impact on pancreatic cancer surgery in central Europe. Guidelines for prompt interventions and prevention of the spread of viral infections in the surgical environment are needed to avoid a deterioration of care in cancer patients in the event of a second wave or a new pandemic. High-volume centers for pancreatic surgery should be preferred and their activity maintained. Virtual conferences have proven to be efficient during this pandemic and should be implemented in the near future.

Elevated circulating levels of secreted frizzled-related protein 4 in relation to insulin resistance and androgens in women with polycystic ovary syndrome.

PURPOSE: Secreted frizzled-related protein 4 (SFRP4) is an adipokine involving in apoptotic process during ovulation and energy metabolism. Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder associated with insulin resistance and impaired oocyte maturation as well as apoptotic dysfunctions through oocyte development. Our aim was to determine whether there was an alteration in levels of SFRP4 and if there was an association between metabolic or hormonal parameters and SFRP4 in women with PCOS. METHODS: We enrolled 80 subjects with PCOS and 80 age- and body mass index (BMI)-matched subjects with normal menstrual cycle into current case-control study. Metabolic and hormonal parameters of enrolled subjects were determined. Circulating SFRP4 levels were measured with ELISA method. RESULTS: We found that circulating SFRP4 levels were elevated in women with PCOS with respect to controls (5.87 ± 1.91 vs. 3.72 ± 1.29 ng/ml, P < 0.001). We also found a positive association between SFRP4 and insulin resistance, androgens, ovarian follicular number or ovarian volume in women with PCOS. Binary logistic regression analysis revealed that subjects with the highest tertile of SFPR4 levels displayed increased possibility of having PCOS risk compared to those subjects with the lowest tertile of SFRP4 levels. CONCLUSIONS: Increased SFRP4 levels were not only associated with higher possibility of having PCOS but also related to insulin resistance, hyperandrogenism, ovarian follicular number and ovarian volume, suggesting that SFPR4 could be a player in different pathophysiologic pathways of PCOS.

Effect of preoperative biliary drainage on bacterial flora in bile of patients with periampullary cancer.

BACKGROUND: Patients with obstructive jaundice due to periampullary tumours may undergo preoperative biliary drainage (PBD). The effect of PBD on the microbiome of the biliary system and on postoperative outcome remains unclear. METHODS: A single-centre retrospective study of patients with obstructive jaundice due to periampullary cancer, treated between July 2007 and July 2015, was undertaken. Intraoperative bile samples were obtained for microbiological analysis after transection of the common bile duct. Postoperative complications were registered. RESULTS: Of 290 patients treated, intraoperative bile samples were present for 172 patients (59·3 per cent) who had PBD and 118 (40·7 per cent) who did not. Contamination of bile was increased significantly in patients who underwent stenting (97·1 per cent versus 18·6 per cent in those without stenting; P < 0·001). PBD resulted in a shift in the biliary microbiome from Escherichia coli in non-stented patients (45 per cent versus 19·2 per cent in stented patients; P = 0·009) towards increased contamination with Enterococcus faecalis (9 versus 37·7 per cent respectively; P = 0·008) and Enterobacter cloacae (0 versus 20·4 per cent; P = 0·033). This shift was associated with a high incidence of bacterial resistance against ampicillin-sulbactam (63·6 per cent versus 18 per cent in patients with no PBD; P < 0·001), piperacillin-tazobactam (30·1 versus 0 per cent respectively; P = 0·003), ciprofloxacin (28·5 versus 5 per cent; P = 0·047) and imipenem (26·6 versus 0 per cent; P = 0·011). The rate of wound infection was higher in patients with a positive bile culture (21·0 per cent versus 6 per cent in patients with sterile bile; P = 0·002). Regression analysis revealed the presence of Enterococcus faecium (odds ratio 2·83, 95 per cent c.i. 1·17 to 6·84; P = 0·021) and Citrobacter species (odds ratio 5·09, 1·65 to 15·71; P = 0·005) as independent risk factors for postoperative wound infection. CONCLUSION: There are fundamental differences in the biliary microbiome of patients with periampullary cancer who undergo PBD and those who do not. PBD induces a shift of the biliary microbiome towards a more aggressive and resistant spectrum, which requires a differentiated perioperative antibiotic treatment strategy.

Assessment of vestibulo-ocular reflex with video head impulse test in epilepsy patients undergoing carbamazepine monotherapy.

OBJECTIVE: Carbamazepine may cause clinical effects such as dizziness and nystagmus. This may depend on the duration of use. The aim of this study is to measure the effect of carbamazepine monotherapy on the vestibular system electrophysiologically by using Video Head Impulse Test (VHIT) and to compare the numerical and objective data obtained between the groups. PATIENTS AND METHODS: In this study, in which 55 people (110 ears) participated, Video Head Impulse Test (VHIT) was performed to evaluate the vestibulo-ocular reflex (VOR) in the epilepsy patients and a healthy control group consisting of healthy individuals. In addition, patients were analyzed in two groups to demonstrate the long-term effects of carbamazepine (<10 years and >10 years). Right/left lateral, anterior, posterior semi-circular canals (SCCs) VOR gains, lateral, left anterior right posterior, and right anterior right posterior gain asymmetries were measured between groups. RESULTS: Lateral SCCs VOR gains were 0.878±0.057 and 0.921±0.045 between the patient and healthy control groups, respectively (p=0.024). A decrease in the right and left lateral SCCs VOR gains (0.885±0.062 and 0.868±0.063) was detected in the patients (p=0.011 and p=0.001). Those using carbamazepine for >10 years had a decrease in lateral SSCs VOR gains (0.843±0.055) compared to those using the drug for <10 years (0.902±0.046) (p=0.008). CONCLUSIONS: A relative reduction in lateral (right/left) SCCs VOR gains was found in epilepsy patients using carbamazepine and in the group of patients using this drug for a long time (>10 years).

Prophylactic glycine administration attenuates pancreatic damage and inflammation in experimental acute pancreatitis.

BACKGROUND/AIMS: Acute pancreatitis (AP) is characterized by premature zymogen activation, systemic inflammatory response resulting in inflammatory infiltrates, sustained intracellular calcium, neurogenic inflammation and pain. The inhibitory neurotransmitter and cytoprotective amino acid glycine exerts a direct inhibitory effect on inflammatory cells, inhibits calcium influx and neuronal activation and therefore represents a putative therapeutic agent in AP. METHODS: To explore the impact of glycine, mild AP was induced in rats by supramaximal cerulein stimulation (10 µg/kg BW/h) and severe AP by retrograde injection of sodium taurocholate solution (3%) into the common biliopancreatic duct. 100/300 mmol glycine was administered intravenously before induction of AP. To elucidate the effect of glycine on AP, we determined pathomorphology, pancreatic cytokines as well as proteases, serum lipase and amylase, pancreatic and lung MPO activity and pain sensation. RESULTS: Glycine administration resulted in a noticeable improvement of pathomorphological alterations in AP, such as a reduction of necrosis, inflammatory infiltrates and cytoplasmic vacuoles in cerulein pancreatitis. In taurocholate pancreatitis, glycine additionally diminished pancreatic cytokines and MPO activity, as well as serum lipase and amylase levels. CONCLUSIONS: Glycine reduced the severity of mild and much more of severe AP by attenuating the intrapancreatic and systemic inflammatory response. Therefore, glycine seems to be a promising tool for prophylactic treatment of AP. and IAP.

Disorders of the enteric nervous system - a holistic view.

The enteric nervous system (ENS) is the largest division of the peripheral nervous system and closely resembles components and functions of the central nervous system. Although the central role of the ENS in congenital enteric neuropathic disorders, including Hirschsprung disease and inflammatory and functional bowel diseases, is well acknowledged, its role in systemic diseases is less understood. Evidence of a disordered ENS has accumulated in neurodegenerative diseases ranging from amyotrophic lateral sclerosis, Alzheimer disease and multiple sclerosis to Parkinson disease as well as neurodevelopmental disorders such as autism. The ENS is a key modulator of gut barrier function and a regulator of enteric homeostasis. A 'leaky gut' represents the gateway for bacterial and toxin translocation that might initiate downstream processes. Data indicate that changes in the gut microbiome acting in concert with the individual genetic background can modify the ENS, central nervous system and the immune system, impair barrier function, and contribute to various disorders such as irritable bowel syndrome, inflammatory bowel disease or neurodegeneration. Here, we summarize the current knowledge on the role of the ENS in gastrointestinal and systemic diseases, highlighting its interaction with various key players involved in shaping the phenotypes. Finally, current flaws and pitfalls related to ENS research in addition to future perspectives are also addressed.

Association of bacteria in pancreatic fistula fluid with complications after pancreatic surgery.

BACKGROUND: Pancreatic fistula (PF) is a common complication after pancreatic surgery. It is unclear how microbes in PF fluid affect outcomes and which microbes are present after pancreatoduodenectomy (PD) and distal pancreatectomy (DP). The aim of this study was to compare the microbiological spectrum of PF fluid after PD versus DP, and its association with postoperative complications. METHODS: Bacterial strains and antibiotic resistance rates of bacterial swabs obtained from the PF fluid of patients who underwent DP or PD were analysed. Cultured bacteria were classified as Enterobacterales and as 'other intestinal and non-intestinal microorganisms' based on whether they are typically part of the normal human intestinal flora. RESULTS: A total of 847 patients had a pancreatic resection (PD 600; DP 247) between July 2007 and December 2016. Clinically relevant PF was detected in 131 patients (15·5 per cent). Bacterial swabs were obtained from 108 patients (DP 47; PD 61), of which 19 (17·6 per cent) were sterile. Enterobacterales were detected in 74 per cent of PF fluid swabs after PD, and in 34 per cent after DP. Infected, polymicrobial or multidrug-resistant PF fluid was more common after PD (rates of 95, 50 and 48 per cent respectively) than after DP (66, 26 and 6 per cent respectively). Patients with higher grade complications (Clavien-Dindo grade IV-V) or grade C PF had more Enterobacterales and multidrug-resistant Enterobacterales in the PF fluid after DP. CONCLUSION: Enterobacterales and multidrug-resistant bacteria are detected frequently after PD and DP, and are associated with more severe complications and PF in patients undergoing DP.

ANTECEDENTES: La fístula pancreática (pancreatic fistula, PF) es una complicación frecuente de la cirugía pancreática. No está claro cómo los microorganismos que se encuentran en el líquido de la PF (pancreatic fistula fluid, PFF) afectan los resultados y qué microbios están presentes después de la duodenopancreatectomía (pancreaticoduodenectomy, PD) y de la pancreatectomía distal (distal pancreatectomy, DP). El objetivo de este estudio fue comparar el espectro microbiológico del PFF después de PD versus DP y su asociación con las complicaciones postoperatorias. MÉTODOS: Se analizaron las cepas bacterianas y las tasas de resistencia a los antibióticos de las muestras bacterianas obtenidas del PFF de pacientes de nuestra institución que se sometieron a DP o PD. Las bacterias identificadas en los cultivos se clasificaron en "enterobacterias" y "otros microorganismos intestinales y no intestinales" en función de si típicamente forman parte de la flora intestinal humana normal o no. RESULTADOS: Un total de 847 pacientes se sometieron a resección pancreática (PD: 600, DP: 247) entre julio de 2007 y diciembre de 2016, y se detectó FP clínicamente relevante en 131 pacientes (15,5%). Se obtuvieron muestras bacterianas de 108 pacientes (DP n = 47, PD N = 61), de los cuales 19 (18%) eran estériles. Se detectaron enterobacterias en el 74% del PFF después de PD y en el 34% después de DP. El PFF infectado, con flora polimicrobiana o flora multirresistente fue más frecuente después de la PD (95,1%, 50%, 47,5%, respectivamente) que después de la DP (66,0%, 25,8%, 6,4%, respectivamente). Los pacientes con complicaciones de grado superior (Clavien-Dindo 4/5) o PF grado C presentaron más enterobacterias y enterobacterias multirresistentes en el PFF después de DP. CONCLUSIÓN: Las enterobacterias y las bacterias multirresistentes se detectaron con frecuencia después de la PD y la DP, y se asociaron a complicaciones más graves y PF en pacientes sometidos a DP.

Nanoplankton population dynamics and dissolved oxygen change across the Bay of Izmir by neural networks.

The bay of Izmir, which is the biggest harbor on the Aegean Sea, is of upmost economical importance for Izmir, the third largest city in Turkey. Most of the studies carried out focused on the effects of intensive industrial activity and agricultural production on the bay pollution within the region. These studies, most of the time, are limited to monitoring the level of pollution. However, it is believed that these studies should be supported with models and statistical analysis techniques, as the models, especially the prediction ones, provide an important approach to assessing risk and assessment. In this study, neural network analysis was used to construct prediction models for nanoplankton population change with nutrients and other environmentally important parameters. The results indicated that, using data over a 52 week period, it is possible to predict nanoplankton population dynamics and dissolved oxygen change for the future.

Outcomes of arterial switch operation for Taussig-Bing anomaly versus transposition of great arteries and ventricular septal defect.

BACKGROUND: This study aims to present the outcomes of arterial switch operation for Taussig-Bing anomaly versus transposition of the great arteries and ventricular septal defect. METHODS: Between November 2010 and December 2016, a total of 100 consecutive arterial switch operations in 42 pediatric patients (25 males, 17 females; median age 17 days; range, 2 to 210 days) were performed in two centers. Among them, 42 patients had associated ventricular septal defect and were diagnosed with Taussig-Bing anomaly (n=15) or transposition of the great arteries and ventricular septal defect (n=27). Aortic arch anomalies were present in six patients (40%) with Taussig-Bing anomaly and two patients (7.4%) with transposition of the great arteries and ventricular septal defect (p=0.016). Coronary anomaly was observed in five (33.3%) and six (22.2%) patients, respectively. All patient had a large defect (multiple n=4), except for eight patients who had moderate defect in the transposition of the great arteries group. RESULTS: Early mortality was 13.3% in the Taussig-Bing anomaly group and 7.4% in the other group. Extracorporeal membrane oxygenation support was needed in three patients. Delayed sternal closure was used in most of the patients (92.9%). The median length of intensive care unit and hospital stays were similar between the groups. The median follow-up was 16 (range, 1 to 50) months. Two patients including one planned (debanding and multiple defect closure) and one unplanned (residual defect closure) were reoperated. Three patients needed aortic balloon angioplasty due to recoarctation and one patient underwent pulmonary balloon angioplasty. Overall reintervention rate was 18.4%. CONCLUSION: Although the incidence of aortic arch and coronary anomalies were higher in patients with Taussig-Bing anomaly, early and mid-term results were similar. Based on these results, primary arterial switch operation seems to be successfully performed for both pathologies.