Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174: 01/27/19

Κυριακή 27 Ιανουαρίου 2019

Feasibility of Image Registration for Ultrasound-Guided Prostate Radiotherapy Based on Similarity Measurement by a Convolutional Neural Network

Technology in Cancer Research &Treatment, Volume 18, Issue , January 2019.

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Charged particle spectrometry to measure 10 B concentration in bone

Abstract

Osteosarcoma is the most common primary malignant tumour of bone in young patients. The survival of these patients has largely been improved due to adjuvant and neo-adjuvant chemotherapy in addition to surgery. Boron neutron capture therapy (BNCT) is proposed as a complementary therapy, due to its ability to inactivate tumour cells that may survive the standard treatment and that may be responsible for recurrences and/or metastases. BNCT is based on neutron irradiation of a tumour enriched in ¹⁰B with a boron-loaded drug. Low-energy neutron capture in ¹⁰B creates charged particles that impart a high dose to tumour cells, which can be calculated only knowing the boron concentration. Charged particle spectrometry is a method that can be used to quantify boron concentration. This method requires acquisition of the energy spectra of charged particles such as alpha particles produced by neutron capture reactions in thin tissue sections irradiated with low-energy neutrons. Boron concentration is then determined knowing the stopping power of the alpha particles in the sample material. This paper describes the adaptation of this method for bone, with emphasis on sample preparation, experimental set-up and stopping power assessment of the involved alpha particles. The knowledge of boron concentration in healthy bones is important, because it allows for any dose limitation that might be necessary to avoid adverse effects such as bone fragility. The measurement process was studied through Monte Carlo simulations and analytical calculations. Finally, the boron content of bone samples was measured by alpha spectrometry at the TRIGA reactor in Pavia, Italy, and compared to that obtained by neutron autoradiography. The agreement between the results obtained with these techniques confirms the suitability of alpha spectrometry to measure boron in bone.

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The influence of prior ramucirumab treatment on the clinical activity of FOLFIRI as third-line therapy in patients with metastatic gastric Cancer

Summary

Purpose Few data described the activity of chemotherapy after ramucirumab plus paclitaxel progression in metastatic gastric cancer patients. The aim of this phase II study is to assess the efficacy and safety of the FOLFIRI regimen as a third-line of treatment. Methods The study enrolled patients with histologically proven metastatic gastric cancer or gastroesophageal junction carcinoma whose disease had progressed after ramucirumab-based second line of treatment. Treatment consisted of biweekly irinotecan 150 mg/m2 as a 1-h infusion on day 1, folinic acid 100 mg/m2 intravenously on days 1–2, and 5-fluorouracil as a 400 mg/m2 bolus and then 600 mg/m2 continuous infusion over 22 h on days 1–2. Primary end-point was tumor response rate (confirmed complete and partial response). Results Twenty-six patients were enrolled. Overall response rate and disease control rate were 11.5% and 38.5%. The median progression free survival (PFS) was 52 days (95% CI:42–74), and the median overall survival was 117 days (95% CI: 94–154). no unexpected adverse events have been observed. A longer PFS and OS were observed in patients who had achieved PFS ≥ 3 months during prior ramucirumab treatment. Conclusions Our findings suggest a poor efficacy of the FOLFIRI regimen in metastatic gastric or gastroesophageal junction cancer patients whose disease progressed during a ramucirumab-based second line of treatment. However, FOLFIRI could be an option for patients who responded to prior ramucirumab.

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Mechanomyography-based muscle fatigue detection during electrically elicited cycling in patients with spinal cord injury

Abstract

Patients with spinal cord injury (SCI) benefit from muscle training with functional electrical stimulation (FES). For safety reasons and to optimize training outcome, the fatigue state of the target muscle must be monitored. Detection of muscle fatigue from mel frequency cepstral coefficient (MFCC) feature of mechanomyographic (MMG) signal using support vector machine (SVM) classifier is a promising new approach. Five individuals with SCI performed FES cycling exercises for 30 min. MMG signals were recorded on the quadriceps muscle group (rectus femoris (RF), vastus lateralis (VL), vastus medialis (VM)) and categorized into non-fatigued and fatigued muscle contractions for the first and last 10 min of the cycling session. For each subject, a total of 1800 contraction-related MMG signals were used to train the SVM classifier and another 300 signals were used for testing. The average classification accuracy (4-fold) of non-fatigued and fatigued state was 90.7% using MFCC feature, 74.5% using root mean square (RMS), and 88.8% with combined MFCC and RMS features. Inter-subject prediction accuracy suggested training and testing data to be based on a particular subject or large collection of subjects to improve fatigue prediction capacity.

Graphical abstract

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Fluorescence microscopy image classification of 2D HeLa cells based on the CapsNet neural network

Abstract

The development of computer technology now allows the quick and efficient automatic fluorescence microscopy generation of a large number of images of proteins in specific subcellular compartments using fluorescence microscopy. Digital image processing and pattern recognition technology can easily classify these images, identify the subcellular location of proteins, and subsequently carry out related work such as analysis and investigation of protein function. Here, based on a fluorescence microscopy 2D image dataset of HeLa cells, the CapsNet network model was used to classify ten types of images of proteins in different subcellular compartments. Capsules in the CapsNet network model were trained to capture the possibility of certain features and variants rather than to capture the characteristics of a specific variant. The capsule at the same level predicted the instantiation parameters of the higher level capsule through the transformation matrix, and the higher level capsule became active when multiple dynamic routing forecasts were consistent. Experiments show that using the CapsNet network model to classify 2D HeLa datasets can achieve higher accuracy.

Graphical abstract

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The impact of environmental pollution on the quality of mother's milk

Abstract

Breastfeeding is a gold standard of neonate nutrition because human milk contains a lot of essential compounds crucial for proper development of a child. However, milk is also a biofluid which can contain environmental pollution, which can have effects on immune system and consequently on the various body organs. Polychlorinated biphenyls are organic pollutants which have been detected in human milk. They have lipophilic properties, so they can penetrate to fatty milk and ultimately to neonate digestive track. Another problem of interest is the presence in milk of heavy metals—arsenic, lead, cadmium, and mercury—as these compounds can lead to disorders in production of cytokines, which are important immunomodulators. The toxicants cause stimulation or suppression of this compounds. This can lead to health problems in children as allergy, disorders in the endocrine system, end even neurodevelopment delay and disorder. Consequently, correlations between pollutants and bioactive components in milk should be investigated. This article provides an overview of environmental pollutants found in human milk as well as of the consequences of cytokine disorder correlated with presence of heavy metals.

Graphical abstract

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"J Drugs Dermatol"[jour]; +20 new citations

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

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Tumors of low malignant potential a single institution experience.

Tumors of low malignant potential a single institution experience.

Int J Surg Case Rep. 2019 Jan 19;55:41-46

Authors: Jbir I, Ghalleb M, Triki A, Zemni I, Hechiche M, Ben Hassouna J, Rahal K

Abstract
BACKGROUND: The tumors of low malignant potential are an independent group of the ovarian epithelial tumors. They represents 10-20% of all ovarian epithelial tumors. Our aim through this study to determine how to treat this disease in the most suitable way.
METHODS: A retrospective study involving 73 patients diagnosed with TLMP and treated at our Institute between September 1975 and June 2010.
RESULTS: The median age was 49 years. In 33% of the cases, the patients were younger than 40 years. Our study included 38 mucinous tumors, 30 serous and 5 mixed. The tumors were stage I in 69% of the cases, stage II in 11% and stage III in 20%. All patients had surgery as a primary treatment. The surgery was radical in 77% of the cases. Five patients had an adjuvant chemotherapy. After a mean follow up of 10 years, we reported 7 cases of local relapses. The prognostic factors for a disease free survival were: the stage of the tumor and the presence of invasive implants. The overall survival at 5 and 10 years was respectively of 96.9% and 92.8%. The prognostic factors for overall survival were: the age, the stage, the existence of a residual tumor, the presence of pseudomyxoma or peritoneal implants. After having a conservative surgery two patients achieved full term pregnancies.
CONCLUSION: Randomized studies are required to back-up our findings and give a higher grade of recommendation to the actual standard of care.

PMID: 30684818 [PubMed - as supplied by publisher]

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Surgical managements of pseudoepitheliomatous keratotic and micaceous balanitis: A case report.

Surgical managements of pseudoepitheliomatous keratotic and micaceous balanitis: A case report.

Int J Surg Case Rep. 2019 Jan 19;55:37-40

Authors: Kim JY, Kim JY, Park M, Oh CK, Chung JS, Park SH, Kim SC

Abstract
INTRODUCTION: Pseudoepitheliomatous keratotic and micaceous balanitis (PKMB) is an extremely rare disease. Herein, we report a case of PKMB in a patient who underwent two surgical procedures, since the 5-FU cream was not available.
PRESENTATION OF CASE: A 50 year-old Korean man undergoing circumcision in a local clinic presented with a tumor-like lesion on the glans penis. Peeling the mass was performed to remove the entire mass after an excisional biopsy. A pathologic finding of mass showed hyperkeratotic and papillomatous squamous epithelium without obvious cytologic atypia. Considering that the lesion recurred after 4 weeks, the patient underwent glansectomy with split-thickness skin graft (STSG). There had been no evidence of recurrence at the surgical site during the follow-up at 6 years postoperatively.
DISCUSSION: If the 5-FU cream is not available, two surgical procedures can be performed for treatment and biopsy. Peeling the mass has the advantage of confirming the characteristics of the whole lesion, but it cannot confirm tumor invasion because it is unable to obtain the subepithelial layer. Glansectomy is able to accurately identify the tumor stage because it removes the tumor and total glans penis and has excellent outcome.
CONCLUSION: PKMB is very rare and has a characteristic appearance, which is mica-like crusts and keratotic horny mass on the glans penis. Glansectomy with STSG is a good procedure when the 5-FU cream was not available.

PMID: 30684817 [PubMed - as supplied by publisher]

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Accessory nipple over the right scapula of a 14-year-old boy: An extremely rare and unreported location, case report.

Accessory nipple over the right scapula of a 14-year-old boy: An extremely rare and unreported location, case report.

Int J Surg Case Rep. 2019 Jan 19;55:35-36

Authors: Mohammed AA

Abstract
INTRODUCTION: Accessory or supernumerary nipples can be applied when more than 2 breasts present in human beings. Usually they are seen in the embryonic milk line; however, their presence outside this line is extremely rare. A 14-year-old boy presented to the surgical consultation room complaining from a round brown skin lesion over the right shoulder area, there were no symptoms associated with this lesion but the family was worried about it. During examination the lesion was diagnosed on the basis of clinical examination and appearance as a supernumerary nipple located over the right scapula. This is an extremely rare location, and no case has been reported before. The family was reassured about the diagnosis that this condition is congenital and the patient discharged with no specific treatment.
CONCLUSION: Accessory nipple is not uncommon, and may present in some rare locations. The main work up should be reassurance of the patient about the diagnosis, and most patients need no intervention however it may be removed for cosmetic concerns, if enlarge in size, or associated with any symptom.

PMID: 30684816 [PubMed - as supplied by publisher]

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Laparoscopic subtotal cholecystectomy for Mirizzi syndrome: A report of a case.

Laparoscopic subtotal cholecystectomy for Mirizzi syndrome: A report of a case.

Int J Surg Case Rep. 2019 Jan 19;55:32-34

Authors: Kimura J, Takata N, Lefor AK, Kanzaki M, Mizokami K

Abstract
INTRODUCTION: Mirizzi syndrome is a rare complication of gallstone disease. The purpose of this report is to describe the utility of laparoscopic subtotal cholecystectomy for Mirizzi syndrome.
PRESENTATION OF CASE: A 53-year-old female presented with dark urine and right upper quadrant pain. Blood tests revealed elevated liver and biliary enzyme levels. Magnetic resonance cholangiopancreatography showed a narrowed common hepatic duct compressed by a large gallstone, consistent with Mirizzi syndrome. Semi-urgent laparoscopic cholecystectomy was planned. At operation, circumferential dissection of the gallbladder neck was difficult. The fundus of the gallbladder was opened and a 2 cm stone extracted. The gallbladder neck was sutured and a drain placed. The postoperative clinical course was uneventful.
DISCUSSION: After laparoscopic cholecystectomy in patients with Mirizzi syndrome, complication rates, including bile duct injuries, is high. In patients with Mirizzi syndrome, removal of the responsible stone is the main purpose of treatment.
CONCLUSION: Laparoscopic subtotal cholecystectomy is a useful technique for patients with Mirizzi syndrome to avoid bile duct injury.

PMID: 30684815 [PubMed - as supplied by publisher]

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Pseudoaneurysm rupture causing hemoperitoneum following rectal impalement injury: A case report.

Pseudoaneurysm rupture causing hemoperitoneum following rectal impalement injury: A case report.

Int J Surg Case Rep. 2019 Jan 19;55:28-31

Authors: Choi PW

Abstract
INTRODUCTION: Although vascular anatomy of the rectum is complex, pseudoaneurysm followed by massive hemoperitoneum after rectal impalement injury is extremely rare.
CASE PRESENTATION: A 43-year-old man presented with abdominal distension. One day earlier, he had undergone sigmoid loop colostomy for rectal implement injury at a local hospital. After the operation, he had become hemodynamically unstable. Digital rectal examination showed a penny-sized anterior rectal wall defect 6 cm from the anal verge. Computed tomography (CT) revealed a hematoma (12 × 10 × 15 cm) with bleeding in the pelvic cavity and an adjacent pseudoaneurysm in the rectum. A large amount of blood and massive hematoma were evacuated by surgery. The Hartmann procedure was performed, but the pseudoaneurysm was not resected. On the 11th postoperative day, hemoglobin decreased (11.6 g/dL-7.9 g/dL), and CT revealed a recurrent hematoma (6.0 × 4.2 cm) in the pelvic cavity, with a residual pseudoaneurysm. Angiography failed to localize the pseudoaneurysm. Consequently, prophylactic embolization at the anterior branch of both the internal iliac arteries was performed. The subsequent hospitalization course was uneventful.
DISCUSSION: Rectal impalement injury may result in pseudoaneurysm of the rectal arteries. However, pseudoaneurysm rupture of the mid rectal artery, followed by massive hemoperitoneum, has not been reported in the English literature. From our experience, preoperative diagnosis of a pseudoaneurysm is crucial for definite surgical management. When surgical resection is indicated, it should include the underlying pseudoaneurysm.
CONCLUSION: Although pseudoaneurysm rupture causing hemoperitoneum after a rectal impalement injury is extremely rare, meticulous preoperative evaluation is necessary for correct management.

PMID: 30684814 [PubMed - as supplied by publisher]

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Acute limb ischemia caused by ruptured cardiac hydatid cyst - A case report.

Acute limb ischemia caused by ruptured cardiac hydatid cyst - A case report.

Int J Surg Case Rep. 2019 Jan 14;55:18-22

Authors: Al-Hakkak SMM, Al-Faham FSM, Al-Awwady AN

Abstract
INTRODUCTION: Acute limb ischemia is a sudden decrease in limb perfusion that threatens the viability of the limb. Complete or even partial occlusion of the arterial supply to a limb can lead to rapid ischemia and poor functional outcomes within hours. In human echinococcosis cardiac involvement is a rare presentation, it may lead to life-threatening complications including cyst rupture; anaphylactic shock; tamponade; pulmonary, cerebral or peripheral arterial embolism. Cardiac hydatid cyst (CHC) may have different presentation include acute lower limb ischemia secondary to embolization from a ruptured cyst.
CASE PRESENTATION: We report an 18-year old male healthy building worker while he was working who presented with sudden onset acute right lower limb pain and paresthesia caused by rupture of primary CHC which managed as a surgical emergency.
DISCUSSION: Clinical presentation of ruptured of CHC depends on the specific location of the ruptured cyst that interferes and mobilization of daughter cyst that logged in vascular system with the function of the surrounding cardiac structures like our case that present with embolization of daughter cyst into the right external iliac artery which leads to acute limb ischemia.
CONCLUSION: Cardiac hydatid cyst is a rare finding with a wide range of signs and symptoms. We are reporting this case to underline that cardiac hydatidosis should be considered as a differential diagnosis in young patients who suddenly develop acute limb ischaemic without a history of both cardiac diseases and trauma that lives in endemic regions of hydatidosis.

PMID: 30684813 [PubMed - as supplied by publisher]

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Euglycemic Ketoacidosis in Spinal Muscular Atrophy

Euglycemic ketoacidosis is defined by the triad of high anion gap acidosis, increased plasma ketones, and the absence of hyperglycemia. Apart from diabetes mellitus, the disorder may occur in prolonged fasting, excessive alcohol consumption, pregnancy, and inborn errors of metabolism. Here, we highlight the diagnosis of euglycemic ketoacidosis in a pediatric nondiabetic patient with spinal muscular atrophy (SMA) type 1 (Werdnig–Hoffmann disease), who, subsequently to her postoperative admission to the intensive care unit following a spinal surgery, developed high anion gap metabolic acidosis. We discuss the pathophysiology of acid-base disorders in SMA, along with the glucose and fatty acids metabolism, the necessary knowledge for medical practitioners.

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High-Dose RAI Therapy Justified by Pathological N1a Disease Revealed by Prophylactic Central Neck Dissection for cN0 Papillary Thyroid Cancer Patients: Is it Superior to Low-Dose RAI Therapy?

High-Dose RAI Therapy Justified by Pathological N1a Disease Revealed by Prophylactic Central Neck Dissection for cN0 Papillary Thyroid Cancer Patients: Is it Superior to Low-Dose RAI Therapy?

World J Surg. 2019 Jan 25;:

Authors: Wei L, Bai L, Zhao L, Yu T, Ma Q, Ji B

Abstract
OBJECTIVE: One of the presumed advantages of prophylactic central neck dissection (pCND) is offering staging basis for more aggressive radioactive iodine (RAI) therapy, which postulates the necessity of high dose for treatment efficacy. The present study aims to compare the effectiveness between low-dose and high-dose RAI in a select cohort of cN0 papillary thyroid cancer (PTC) patients with pathological N1a (pN1a) disease revealed by pCND in terms of ablation rate and response to therapy. The frequency of short-term adverse effects between the two groups was also compared.
PATIENTS AND METHODS: From January 2014 to April 2016, cN0 PTC patients with pN1a disease revealed by pCND in our hospital were retrospectively reviewed. Patients with other indications for high-dose RAI, such as the presence of extrathyroidal extension, vascular invasion or suspicions of distant metastasis, were excluded. For the included patients, high dose (3700 MBq) was administered between January 2014 and August 2015 and low dose (1110 MBq) between August 2015 and April 2016. Ablation assessment was performed 6 months after RAI therapy. Response evaluation after RAI therapy was performed after 46.3 ± 9.5 months for high-dose group and 29.1 ± 2.6 months for low-dose group. All patients were also evaluated for short-term adverse effects 24 and 72 hours after RAI administration.
RESULTS: A total of 84 patients were enrolled. Among them, 42 were in the high-dose group and the other 42 in the low-dose group. There was no significant difference in ablation rate (P = 0.7707) and response to RAI therapy (P = 0.6454) between the two groups. Twenty-four hours after RAI administration, neck pain and swelling (33.3% VS. 11.9%; P = 0.0372) and gastrointestinal discomfort (45.2% vs. 21.4%; P = 0.0373) were significantly more frequent in the high-dose group.
CONCLUSION: High-dose RAI therapy, with higher frequency of short-term adverse effects, appears to be not superior to low-dose RAI therapy for cN0 PTC patients with pN1a disease revealed by pCND to achieve better response to therapy. Further randomized studies with larger series of patients and longer follow-up duration, especially with the low-dose group, are needed to validate our results.

PMID: 30684002 [PubMed - as supplied by publisher]

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Early Acute Kidney Injury Within an Established Enhanced Recovery Pathway: Uncommon and Transitory.

Early Acute Kidney Injury Within an Established Enhanced Recovery Pathway: Uncommon and Transitory.

World J Surg. 2019 Jan 25;:

Authors: Grass F, Lovely JK, Crippa J, Mathis KL, Hübner M, Larson DW

Abstract
BACKGROUND: The present study aimed to assess the impact of perioperative fluid management on early acute kidney injury (AKI) rate and long-term sequelae in patients undergoing elective colorectal procedures within an enhanced recovery pathway (ERP).
METHODS: Retrospective analysis of consecutive patients from a prospectively maintained ERP database (2011-2015) is performed. Pre- and postoperative creatinine levels (within 24 h) were compared according to risk (preoperative creatinine rise ×1.5), injury (×2), failure (×3), loss of kidney function and end-stage kidney disease (RIFLE) criteria. Risk factors for early AKI were identified through logistic regression analysis, and long-term outcome in patients with AKI was assessed.
RESULTS: Out of 7103 patients, 4096 patients (58%) with pre- and postoperative creatinine levels were included. Of these, 104 patients (2.5%) presented postoperative AKI. AKI patients received higher amounts of POD 0 fluids (3.8 ± 2.4 vs. 3.2 ± 2 L, p = 0.01) and had increased postoperative weight gain at POD 2 (6 ± 4.9 vs. 3 ± 2.7 kg, p = 0.007). Independent risk factors for AKI were high ASA score (ASA ≥ 3: OR 1.7; 95% CI 1.1-2.5), prolonged operating time (>180 min: OR 1.9; 95% CI 1.3-2.9) and diabetes mellitus (OR 2.5; 95% CI 1.5-4), while minimally invasive surgery was a protective factor (OR 0.6; 95% CI 0.4-0.9). Five patients (0.1%) developed chronic kidney disease, and two of them needed dialysis after a mean follow-up of 33.7 ± 22.4 months.
CONCLUSIONS: Early AKI was very uncommon in the present cohort of colorectal surgery patients treated within an ERP, and long-term sequelae were exceptionally low.

PMID: 30684001 [PubMed - as supplied by publisher]

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Surgical Procedures Performed by Emergency Medical Teams in Sudden-Onset Disasters: A Systematic Review.

Surgical Procedures Performed by Emergency Medical Teams in Sudden-Onset Disasters: A Systematic Review.

World J Surg. 2019 Jan 24;:

Authors: Coventry CA, Vaska AI, Holland AJA, Read DJ, Ivers RQ

Abstract
BACKGROUND: Emergency medical teams (EMTs) frequently provide surgical care after sudden-onset disasters (SODs) in low- and middle-income countries. The purpose of this review is to describe the types of surgical procedures performed by EMTs with general surgical capability in order to aid the recruitment and training of surgeons for these teams.
METHODS: A search of electronic databases (PubMed, MEDLINE, and EMBASE) was carried out to identify articles published between 1990 and 2018 that describe the type of surgical procedures performed by EMTs in the impact and post-impact phases of a SOD. Further relevant articles were obtained by hand searching reference lists.
RESULTS: A total of 16 articles met the inclusion criteria. Articles reporting on EMTs from a number of different countries and responding to a variety of SODs were included. There was a high prevalence of procedures for extremity soft tissue injuries (46.8%) and fractures (28.3%), although a number of abdominal and genitourinary/obstetric procedures were also reported.
CONCLUSIONS: Based upon this review, deployment of surgeons or teams with experience in the management of soft tissue wounds, orthopaedic trauma, abdominal surgery, and obstetrics is recommended.

PMID: 30680503 [PubMed - as supplied by publisher]

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Fast-Track Pancreaticoduodenectomy: Factors Associated with Early Discharge.

Fast-Track Pancreaticoduodenectomy: Factors Associated with Early Discharge.

World J Surg. 2019 Jan 24;:

Authors: Mahvi DA, Pak LM, Bose SK, Urman RD, Gold JS, Whang EE

Abstract
BACKGROUND: Pancreaticoduodenectomy is a complex surgery frequently associated with prolonged hospitalizations. However, there are a subset of patients discharged within 5 days from surgery; the preoperative and intraoperative characteristics of this subset are unknown.
METHODS: The NSQIP Targeted Pancreatectomy Dataset was used from 2014 to 2016. Patients who died within 30 days were excluded. A total of 10,741 patients undergoing pancreaticoduodenectomy were identified. Univariable and multivariable logistic regression analyses were performed for preoperative and intraoperative ACS-NSQIP variables to identify predictors of early discharge. Early discharge was defined as discharge 3-5 days after surgery.
RESULTS: A total of 1105 patients (10.3%) were discharged within 5 days following pancreaticoduodenectomy. On multivariable analysis, preoperative factors associated with early discharge included younger age (OR 0.988, p < 0.001), non-obesity (OR 0.737, p = 0.001), those receiving neoadjuvant chemotherapy (OR 1.424, p < 0.001), and lack of COPD (OR 0.489, p = 0.005) or hypertension (OR 0.805, p = 0.007). Intraoperative factors associated with early discharge on multivariable analysis were shorter operation duration (OR 0.999, p = 0.002), minimally invasive surgery (OR 3.537, p < 0.001), and hard pancreatic texture (OR 1.480, p < 0.001). Intraoperative factors associated with non-early discharge were epidural placement (OR 0.485, p < 0.001), drain placement (OR 0.308, p < 0.001), and jejunostomy tube placement (OR 0.278, p < 0.001). Patients discharged within 5 days had a 14.7% readmission rate compared to 17.0% for later discharges (p = 0.047).
CONCLUSIONS: Multiple preoperative and intraoperative factors, including some that are potentially modifiable, were significantly associated with early discharge after pancreaticoduodenectomy. Patients with these characteristics may benefit from enhanced recovery after surgery programs and expedited disposition planning postoperatively.

PMID: 30680502 [PubMed - as supplied by publisher]

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Reappraisal of Prognostic Impact of Tumor SUVmax by 18F-FDG-PET/CT in Intrahepatic Cholangiocarcinoma.

Reappraisal of Prognostic Impact of Tumor SUVmax by 18F-FDG-PET/CT in Intrahepatic Cholangiocarcinoma.

World J Surg. 2019 Jan 24;:

Authors: Yoh T, Seo S, Morino K, Fuji H, Ikeno Y, Ishii T, Taura K, Nakamoto Y, Higashi T, Kaido T, Uemoto S

Abstract
BACKGROUND: We previously reported that tumor standardized uptake value (SUVmax) by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) was a potential predictor in patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC). However, the prognostic value of SUVmax in the era of multidisciplinary strategy has remained unclear. The aim of this study was to reappraise the prognostic value of tumor SUVmax in patients undergoing surgery for ICC.
METHODS: Data from 82 consecutive ICC patients, who underwent 18F-FDG-PET/CT and subsequent surgery between 2006 and 2017, were retrieved from a prospectively maintained institutional database. Adjuvant strategy was administrated during this study period in our center.
RESULTS: Tumor SUVmax was associated with tumor size (p = 0.002) and tumor number (p = 0.005), but not associated with T and N stage classified by American Joint Committee on Cancer-classification system, and other tumor factors. According to the tumor SUVmax cut-off values of 8.0 based on the minimum p value approach, actuarial 5-year overall survival (OS) rates in patients undergoing upfront surgery for ICC were significantly stratified at 54.7% versus 26.0% (low vs. high tumor SUVmax group, p = 0.008). The actuarial 3-year disease-free survival (DFS) rates were also significantly stratified at 41.0% versus 18.3% (p < 0.001). Multivariate Cox regression analyses revealed that tumor SUVmax retained its significance on OS (p = 0.039) as well as DFS (p < 0.001).
CONCLUSION: Even in the era of multidisciplinary strategy, high tumor SUVmax still represents poor prognosis in patients undergoing surgery for ICC. These patients, therefore, would probably be required more effective strategies.

PMID: 30680501 [PubMed - as supplied by publisher]

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Letter to Editor: Routine Pathology and Postoperative Follow-Up are Not Cost-Effective in Cholecystectomy for Benign Gallbladder Disease.

Letter to Editor: Routine Pathology and Postoperative Follow-Up are Not Cost-Effective in Cholecystectomy for Benign Gallbladder Disease.

World J Surg. 2019 Jan 24;:

Authors: Garg PK

Abstract

PMID: 30680500 [PubMed - as supplied by publisher]

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Does Primary Hyperparathyroidism Have an Association with Thyroid Papillary Cancer? A Retrospective Cohort Study.

Does Primary Hyperparathyroidism Have an Association with Thyroid Papillary Cancer? A Retrospective Cohort Study.

World J Surg. 2019 Jan 24;:

Authors: Çetin K, Sıkar HE, Temizkan Ş, Ofluoğlu CB, Özderya A, Aydın K, Gül AE, Küçük HF

Abstract
BACKGROUND: To investigate the relationship between primary hyperparathyroidism (pHPT) and papillary thyroid cancer (PTC).
METHODS: The perioperative findings of 275 patients with pHPT who underwent surgery between January 2014 and December 2017 were retrospectively reviewed. Thirty-one patients were diagnosed with pHPT and PTC concurrently. Pathology results and demographic findings of these patients were compared with 186 patients who underwent thyroidectomy and diagnosed with PTC at the same time interval.
RESULTS: The co-occurrence of pHPT and PTC was 11.3% (31/275). The median ages of the pHPT, pHPT + PTC, and PTC groups were 55, 57, and 50 years old, respectively (p < 0.001). The diameter of tumor was smaller in the pHPT + PTC group [median 7 mm (range 0.5-25 mm) vs. 15 mm (range 1-100 mm)], with higher rates of microcarcinomas (p < 0.001), than the patients in the PTC group. Examination of tumor morphology showed higher rates of tumor capsule invasion and multicentricity in the pHPT + PTC group than those in the isolated PTC group (p = 0.02, p = 0.04, respectively).
CONCLUSION: The pHPT + PTC group had significantly smaller tumor diameter than the PTC group. This result may support the idea that pHPT leads to overdiagnosis of PTC. However, observation of high rates of tumor capsule invasion and multicentricity in the pHPT + PTC group may suggest an associative etiology with more aggressive PTC.

PMID: 30680499 [PubMed - as supplied by publisher]

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Letter to the Editor: Perforated Diverticulitis with Generalized Peritonitis: Low Stoma Rate Using a "Damage Control Strategy".

Letter to the Editor: Perforated Diverticulitis with Generalized Peritonitis: Low Stoma Rate Using a "Damage Control Strategy".

World J Surg. 2019 Jan 24;:

Authors: Mattone E, Schembari E, Mannino M, Magazù S, Di Carlo I

Abstract

PMID: 30680498 [PubMed - as supplied by publisher]

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Impact of Diabetes Mellitus on Human Mesenchymal Stromal Cell Biology and Functionality: Implications for Autologous Transplantation.

Impact of Diabetes Mellitus on Human Mesenchymal Stromal Cell Biology and Functionality: Implications for Autologous Transplantation.

Stem Cell Rev. 2019 Jan 24;:

Authors: Mahmoud M, Abu-Shahba N, Azmy O, El-Badri N

Abstract
Multipotent mesenchymal stem/stromal cells (MSCs) have regenerative and immunomodulatory properties to restore and repair injured tissues, making them attractive candidates for cell-based therapies. Experimental and clinical evidence has demonstrated the effectiveness of MSC transplantation in managing diabetes mellitus (DM). Autologous MSCs are assumed to be favorable because patient-derived cells are readily available and do not entail sustained immunosuppressive therapy. DM is associated with hyperglycemia, oxidative stress and altered immune responses and inflammation. It may thus alter the biological characteristics and therapeutic qualities of human MSCs (hMSCs). Several studies have explored the effect of DM or the diabetic microenvironment on the engraftment and efficacy of transplanted MSCs, which are determined by proliferation, differentiation, senescence, angiogenesis supportive effect, migration, anti-oxidative capacity and immunomodulatory properties. This review aims to present the available data on how DM impacts MSC biology and functionality and identify future perspectives for autologous MSC-based therapy in diabetics.

PMID: 30680660 [PubMed - as supplied by publisher]

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Serial Measurements of Left Ventricular Systolic and Diastolic Function by Cardiac Magnetic Resonance Imaging in Patients with Early Stage Breast Cancer on Trastuzumab.

Serial Measurements of Left Ventricular Systolic and Diastolic Function by Cardiac Magnetic Resonance Imaging in Patients with Early Stage Breast Cancer on Trastuzumab.

Am J Cardiol. 2019 Jan 08;:

Authors: Song L, Brezden-Masley C, Swaminathan V, Ghugre N, Barfett JJ, Chan KKK, Haq R, Petrella T, Dhir V, Jimenez-Juan L, Chacko BR, Kotha V, Connelly KA, Yan AT

Abstract
Our aim was to evaluate the temporal changes in left ventricular (LV) diastolic filling in relation to other LV parameters using cardiac MRI (CMR) in patients with HER2 positive breast cancer receiving trastuzumab therapy. Fourty-one women with early stage HER2+ breast cancer underwent serial CMR (baseline, 6, 12, and 18 months) after initiation of trastuzumab therapy. A single, blinded observer measured LV parameters on de-identified CMRs in random order. Linear mixed models were used to investigate temporal changes. Compared to baseline, there were significant decreases in systolic function as measured by both left ventricular ejection fraction (LVEF) (p <0.001 at 6 and 12 months) and peak ejection rate corrected for end-diastolic volume (PER/LVEDV) (p = 0.008 at 6 months, p = 0.01 at 12 months). However, these differences were no longer significant at 18 months. In contrast, significant reductions in diastolic function as measured by LV peak filling rate corrected for end-diastolic volume (PFR/LVEDV) were observed at 6 months (p = 0.012), 12 months (p = 0.031), and up to 18 months (p = 0.034). There were no significant temporal changes in the time to peak filling rate corrected for cardiac cycle (TPF/RR). The reduction in PFR/LVEDV at 18 months was no longer significant when corrected for heart rate. In conclusion, there were significant subclinical deleterious effects on both LV systolic and diastolic function among patients receiving trastuzumab. While there was recovery in LV systolic function after therapy cessation at 18 months, reduction in PFR/LVEDV appeared to persist. Thus, diastolic dysfunction may serve as a marker of trastuzumab-induced cardiotoxicity that needs to be confirmed in a larger study.

PMID: 30683420 [PubMed - as supplied by publisher]

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PET imaging of HER2 expression with an 18F-fluoride labeled aptamer.

PET imaging of HER2 expression with an 18F-fluoride labeled aptamer.

PLoS One. 2019;14(1):e0211047

Authors: Kim HJ, Park JY, Lee TS, Song IH, Cho YL, Chae JR, Kang H, Lim JH, Lee JH, Kang WJ

Abstract
BACKGROUND/PURPOSE: Aptamers are oligonucleotide or peptide molecules that bind to a target molecule with high affinity and specificity. The present study aimed to evaluate the target specificity and applicability for in vivo molecular imaging of an aptamer labeled with a radioisotope.
METHODS: The human epidermal growth factor receptor 2 (HER2/ErbB2) aptamer was radiolabeled with 18F-fluoride. HER2-positive tumor cell uptake of the aptamer was evaluated in comparison to negative controls by flow cytometry and confocal microscopy. Using 18F-labeled HER2-specific aptamer positron emission tomography (PET), in vivo molecular images of BT474 tumor-bearing mice were taken at 60, 90 and 120 minutes after injection.
RESULTS: In flow cytometric analysis, HER2 aptamer showed strong binding to HER2-positive BT474 cells, while binding to HER2-negative MDA-MB231 cells was quite low. Likewise, in confocal microscopic images, the aptamer was bound to HER2-positive breast cancer cells, with minimal binding to HER2-negative cells. In vivo PET molecular imaging of BT474 tumor-bearing mice revealed significant higher uptake of the 18F-labeled HER2 specific aptamer into the tumor compared to the that of HER2-negative cell tumor(p = 0.033). HER2 aptamer was able to preferentially bind to HER2-positive breast cancer cells both in vitro and in vivo, by recognizing HER2 structure on the surface of these cells.
CONCLUSION: The 18F-labeled aptamer enabled appropriate visualization of HER2 expression by human breast cancer cells. The results suggest that a radiolabeled HER2 aptamer could potentially be applied in the development of treatment strategies or in targeted therapy against HER2-positive breast cancer cells.

PMID: 30682091 [PubMed - in process]

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Olmesartan Associated Enteropathy: A Rare Underdiagnosed Cause of Diarrhea and Weight Loss.

Olmesartan Associated Enteropathy: A Rare Underdiagnosed Cause of Diarrhea and Weight Loss.

Am J Case Rep. 2019 Jan 26;20:111-116

Authors: Gonakoti S, Khullar S, Rajkumar A

Abstract
BACKGROUND Olmesartan, an angiotensin receptor blockade class of antihypertensive medication has recently been associated with a seronegative sprue like enteropathy. Patients typically present with diarrhea and weight loss often prompting exhaustive diagnostic workup. Discontinuation of the drug leads to dramatic recovery and hence, physicians need to be aware of olmesartan associated enteropathy (OAE) in order to avoid unnecessary testing. CASE REPORT A 59-year-old Caucasian male was admitted to the hospital with complaints of intractable diarrhea, vomiting and considerable weight loss. Medical history was notable for hypertension being treated with olmesartan. Workup for all potential infectious causes and celiac disease was negative. Eventually, a colonoscopy was performed due to his persistent symptoms and biopsy revealed lymphocytic colitis. An upper endoscopy was also performed, and histopathology of the duodenum revealed total villous blunting. In light of negative serology for celiac disease and after a detailed review of the patient's medications, the possibility of olmesartan induced enteropathy was considered. Olmesartan was stopped and his symptoms resolved. A follow-up endoscopy done a few months later showed normal small bowel mucosa. CONCLUSIONS This case demonstrates the need for a thorough medication review by healthcare providers especially after a full workup for the patient's symptoms has already been performed. It also reiterates that having an awareness of rare side effects of common medications mitigates the need for extensive diagnostic testing.

PMID: 30683835 [PubMed - in process]

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A Case of Acute Exacerbation of Chronic Adrenal Insufficiency Due to Ipilimumab Treatment for Advanced Melanoma.

A Case of Acute Exacerbation of Chronic Adrenal Insufficiency Due to Ipilimumab Treatment for Advanced Melanoma.

Am J Case Rep. 2019 Jan 25;20:106-110

Authors: Sakaguchi C, Yano S, Ashida K, Wada N, Ohe K, Nagata H, Matsuda Y, Sakamoto S, Sakamoto R, Ohnaka K, Uchi H, Furue M, Nomura M, Ogawa Y

Abstract
BACKGROUND Ipilimumab is a therapeutic human monoclonal antibody that targets the T-cell inhibitory molecule, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and is classified as an immune checkpoint inhibitor that has been shown to improve prognosis in patients with advanced melanoma. However, several immune-related adverse events have been reported to be associated with ipilimumab Treatment. A case of acute exacerbation of chronic adrenal insufficiency is presented that highlights that glucocorticoid dosage for patients undergoing steroid treatment at the time of ipilimumab treatment has yet to be established. CASE REPORT A 50-year-old Japanese woman was diagnosed with malignant melanoma on the sole of her right foot. During her second course of ipilimumab treatment, she developed acute adrenal insufficiency caused by isolated adrenocorticotropic hormone (ACTH) deficiency, which required treatment with oral hydrocortisone. However, the symptoms of her adrenal insufficiency worsened, and she commenced treatment with 12 courses of nivolumab, a therapeutic human monoclonal antibody that blocks programmed cell death protein 1 (PD-1) on the surface of T-cells. She did not require corticosteroid support during nivolumab treatment. CONCLUSIONS This case report highlights the risk of exacerbating adrenal insufficiency during treatment with ipilimumab. The differences in clinical outcome in this patient between ipilimumab and nivolumab treatment might be explained by the different mechanisms between ipilimumab and nivolumab on immune function.

PMID: 30679413 [PubMed - in process]

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Outcomes Following Proton Therapy for Pediatric Low-Grade Glioma.

Outcomes Following Proton Therapy for Pediatric Low-Grade Glioma.

Int J Radiat Oncol Biol Phys. 2019 Jan 23;:

Authors: Indelicato DJ, Rotondo RL, Uezono H, Sandler ES, Aldana PR, Ranalli NJ, Beier AD, Morris CG, Bradley JA

Abstract
BACKGROUND/OBJECTIVES: Dosimetric studies show that proton therapy can reduce the low/intermediate radiation dose to uninvolved tissue in children with low-grade glioma (LGG). For this reason, LGG is the 4th most common pediatric tumor treated with proton therapy, yet clinical outcome data on efficacy and toxicity are limited.
DESIGN/METHODS: We reviewed the medical records of 174 children (≤21 years old) with non-metastatic LGG enrolled on a prospective protocol and treated with proton therapy between 2007 and 2017 to assess clinical outcomes and toxicity, and analyze patient, tumor, and treatment-related variables.
RESULTS: Median age was 10.2 years (range, 2-21). Fifty-eight percent of tumors were WHO grade I; 30% WHO grade II; 12% were diagnosed on imaging characteristics alone. The most common histology was pilocytic astrocytoma (47%). The most common tumor subsites were diencephalon/optic pathway (52%), caudal brainstem (17%), and cerebellum (13%). Forty-two percent received chemotherapy before radiotherapy. The median follow-up was 4.4 years. The 5-year actuarial rates of local control, progression-free survival, and overall survival were 85% (95% CI 78-90%), 84% (95% CI 77-89%), and 92% (95% CI 85-95%). On univariate analysis, brainstem/spinal cord tumor location (62% vs. 90% elsewhere) and dose <54 GyRBE (67% vs. 91% for 54 GyRBE) were associated with inferior local control (p <0.01 for both). Twenty-two patients (12.6%) experienced acute nausea or vomiting requiring ondansetron; 2 patients (1.1%) required corticosteroids. Serious toxicities (4% of patients) included brainstem necrosis requiring corticosteroids (n=2), symptomatic vasculopathy (n=2), radiation retinopathy (n=1), epilepsy (n=1), and death from radiation-induced high-grade glioma (n =1). Thirty-nine patients (22%) developed new-onset central hormone deficiency. Pseudoprogression was observed in 32.1%.
CONCLUSION: Compared to modern photon series, proton therapy reduces the radiation dose to developing brain tissue, diminishing acute toxicities without compromising disease control.

PMID: 30684665 [PubMed - as supplied by publisher]

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Dual responsive neurostimulation implants for epilepsy.

Dual responsive neurostimulation implants for epilepsy.

J Neurosurg. 2019 Jan 25;:1-7

Authors: Barbaro MF, Chesney K, Kramer DR, Kellis S, Peng T, Blumenfeld Z, Gogia AS, Lee MB, Greenwood J, Nune G, Kalayjian LA, Heck CN, Liu CY, Lee B

Abstract
Closed-loop brain-responsive neurostimulation via the RNS System is a treatment option for adults with medically refractory focal epilepsy. Using a novel technique, 2 RNS Systems (2 neurostimulators and 4 leads) were successfully implanted in a single patient with bilateral parietal epileptogenic zones. In patients with multiple epileptogenic zones, this technique allows for additional treatment options. Implantation can be done successfully, without telemetry interference, using proper surgical planning and neurostimulator positioning.Trajectories for the depth leads were planned using neuronavigation with CT and MR imaging. Stereotactic frames were used for coordinate targeting. Each neurostimulator was positioned with maximal spacing to avoid telemetry interference while minimizing patient discomfort. A separate J-shaped incision was used for each neurostimulator to allow for compartmentalization in case of infection. In order to minimize surgical time and risk of infection, the neurostimulators were implanted in 2 separate surgeries, approximately 3 weeks apart.The neurostimulators and leads were successfully implanted without adverse surgical outcomes. The patient recovered uneventfully, and the early therapy settings over several months resulted in preliminary decreases in aura and seizure frequency. Stimulation by one of the neurostimulators did not result in stimulation artifacts detected by the contralateral neurostimulator.

PMID: 30684944 [PubMed - as supplied by publisher]

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Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of Tuberous Sclerosis Complex.

Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of Tuberous Sclerosis Complex.

Behav Brain Res. 2019 Jan 23;:

Authors: Serra I, Scheldeman C, Bazelot M, Whalley BJ, Dallas ML, de Witte PAM, Williams CM

Abstract
Tuberous sclerosis complex (TSC) is a rare disease caused by mutations in the TSC1 or TSC2 genes and is characterized by widespread tumour growth, intractable epilepsy, cognitive deficits and autistic behaviour. CBD has been reported to decrease seizures and inhibit tumour cell progression, therefore we sought to determine the influence of CBD on TSC pathology in zebrafish carrying a nonsense mutation in the tsc2 gene. CBD treatment from 6 to 7 days post-fertilization (dpf) induced significant anxiolytic actions without causing sedation. Furthermore, CBD treatment from 3 dpf had no impact on tsc2-/- larvae motility nor their survival. CBD treatment did, however, reduce the number of phosphorylated rpS6 positive cells, and their cross-sectional cell size. This suggests a CBD mediated suppression of mechanistic target of rapamycin (mTOR) activity in the tsc2-/- larval brain. Taken together, these data suggest that CBD selectively modulates levels of phosphorylated rpS6 in the brain and additionally provides an anxiolytic effect. This is pertinent given the alterations in mTOR signalling in experimental models of TSC. Additional work is necessary to identify upstream signal modulation and to further justify the use of CBD as a possible therapeutic strategy to manage TSC.

PMID: 30684511 [PubMed - as supplied by publisher]

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Ketogenic and anaplerotic dietary modifications ameliorate seizure activity in Drosophila models of mitochondrial encephalomyopathy and glycolytic enzymopathy.

Ketogenic and anaplerotic dietary modifications ameliorate seizure activity in Drosophila models of mitochondrial encephalomyopathy and glycolytic enzymopathy.

Mol Genet Metab. 2019 Jan 17;:

Authors: Fogle KJ, Smith AR, Satterfield SL, Gutierrez AC, Hertzler JI, McCardell CS, Shon JH, Barile ZJ, Novak MO, Palladino MJ

Abstract
Seizures are a feature not only of the many forms of epilepsy, but also of global metabolic diseases such as mitochondrial encephalomyopathy (ME) and glycolytic enzymopathy (GE). Modern anti-epileptic drugs (AEDs) are successful in many cases, but some patients are refractory to existing AEDs, which has led to a surge in interest in clinically managed dietary therapy such as the ketogenic diet (KD). This high-fat, low-carbohydrate diet causes a cellular switch from glycolysis to fatty acid oxidation and ketone body generation, with a wide array of downstream effects at the genetic, protein, and metabolite level that may mediate seizure protection. We have recently shown that a Drosophila model of human ME (ATP61) responds robustly to the KD; here, we have investigated the mechanistic importance of the major metabolic consequences of the KD in the context of this bioenergetics disease: ketogenesis, reduction of glycolysis, and anaplerosis. We have found that reduction of glycolysis does not confer seizure protection, but that dietary supplementation with ketone bodies or the anaplerotic lipid triheptanoin, which directly replenishes the citric acid cycle, can mimic the success of the ketogenic diet even in the presence of standard carbohydrate levels. We have also shown that the proper functioning of the citric acid cycle is crucial to the success of the KD in the context of ME. Furthermore, our data reveal that multiple seizure models, in addition to ATP61, are treatable with the ketogenic diet. Importantly, one of these mutants is TPIsugarkill, which models human glycolytic enzymopathy, an incurable metabolic disorder with severe neurological consequences. Overall, these studies reveal widespread success of the KD in Drosophila, further cementing its status as an excellent model for studies of KD treatment and mechanism, and reveal key insights into the therapeutic potential of dietary therapy against neuronal hyperexcitability in epilepsy and metabolic disease.

PMID: 30683556 [PubMed - as supplied by publisher]

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Benefits of the epilepsy specialist nurses (ESN) role, standardized practices and education around the world.

Benefits of the epilepsy specialist nurses (ESN) role, standardized practices and education around the world.

Rev Neurol (Paris). 2019 Jan 22;:

Authors: Prevos-Morgant M, Leavy Y, Chartrand D, Jurasek L, Osborne Shafer P, Shinnar R, Goodwin M

Abstract
Epilepsy, often considered as a stigmatizing disease, affects 65 million people worldwide and is frequently associated with comorbidities that increase both direct and indirect costs. The degree of impact on quality of life and the cost of care differs depending on the social and health care organizations in place, political, medico-economic and/or socio-cultural contexts. Across the globe, healthcare is provided by nurses in primary care, urgent or emergency care, and within specialized domains of practice. In Epilepsy the global care could be enhanced by developing standardized nursing education in close collaboration with other caregivers. The impact of epilepsy nursing care has been documented in some developed countries, but the diversity of nursing practices and professional education of nurses raise difficulties in generalizing these findings. Specialized education in epilepsy will improve access, treatment and ultimately the quality of life of patients.

PMID: 30683450 [PubMed - as supplied by publisher]

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Hairy cell leukemia presenting with Ecthyma Gangrenosum- a case report.

Hairy cell leukemia presenting with Ecthyma Gangrenosum- a case report.

BMC Infect Dis. 2019 Jan 25;19(1):85

Authors: Sluga R, Tersmette M, Sohne M

Abstract
BACKGROUND: Ecthyma gangrenosum is a cutaneous infectious usually associated with P. aeruginosa. It usually develops In patients with an underlying immunodeficiency.
CASE PRESENTATION: A 50-year old mentally disabled white male with a history of epilepsy presented with fever and a painless red macule on his right arm which rapidly progressed to a painful ulcer. Blood and lesion cultures revealed P.aeruginosa, confirming our clinical diagnosis of ecthyma gangrenosum. Subsequently an underlying immune deficit was found, namely patient was diagnosed with hairy-cell leukemia. Despite adequate antibiotics no infection control could be achieved. After treating the underlying immune deficit as well, the infection and hairy-cell leukemia resolved completely.
CONCLUSION: Ecthyma gangrenosum is an important cutaneous infection to recognize, because it is it is typically associated with P.aeruginosa bacteremia. Recognizing this skin leasion should prompt empiric antimicrobial therapy including an agent with antipseudomonal activity. Furthermore, just like in our case, the presence of ecthyma gangrenosum can signal the presence of an occult immune deficit, warranting further investigation.

PMID: 30683071 [PubMed - in process]

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Neurosurgical therapy for Status Epilepticus in Oligoastrocytoma Patient: A case report.

Neurosurgical therapy for Status Epilepticus in Oligoastrocytoma Patient: A case report.

World Neurosurg. 2019 Jan 22;:

Authors: San-Juan D, Álvarez-Perera LÁ, Dávila-Rodríguez DO, Ramos-Jiménez C, Alcocer-Barrada V, Lilia-Tena M, Anschel DJ, Cruz JP, Martínez-Juárez IE

Abstract
BACKGROUND: Super refractory epilepticus status (SRSE) is a life-threatening neurologic emergency defined as 'status epilepticus (SE) that continues 24 hours or more after the onset of anaesthesia, including those cases in which the SE recurs on the reduction or withdrawal of anaesthesia', which occur in 10-15% of SE patients and rarely has been resolved surgically.
METHODS: A 20-year-old man with SRSE and a long history of left parieto-occipital oligoastrocytoma was admitted for convulsive SE that become SRSE and underwent lesionectomy guided by electrocorticography and neuro-navigation for local tumor recurrence. Histopathological diagnosis was oligoastrocytoma.
RESULTS: SRSE was aborted and the patient recovery fully without any functional deficits.
CONCLUSIONS: The lesionectomy guided by electrocorticography and neuro- navigation should be considered as a treatment option for patients with SRSE.

PMID: 30682510 [PubMed - as supplied by publisher]

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Medication treatment for attention-deficit/hyperactivity disorder and the risk of acute seizures in individuals with epilepsy.

Medication treatment for attention-deficit/hyperactivity disorder and the risk of acute seizures in individuals with epilepsy.

Epilepsia. 2019 Jan 25;:

Authors: Brikell I, Chen Q, Kuja-Halkola R, D'Onofrio BM, Wiggs KK, Lichtenstein P, Almqvist C, Quinn PD, Chang Z, Larsson H

Abstract
OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) affects 10%-30% of individuals with epilepsy, yet concerns remain regarding the safety of ADHD medication in this group. The objective of this study was to examine the risk of acute seizures associated with ADHD medication in individuals with epilepsy.
METHODS: A total of 21 557 individuals with a seizure history born between 1987 and 2003 were identified from Swedish population registers. Within this study population, we also identified 6773 youth (<19 years of age) who meet criteria for epilepsy, and 1605 youth with continuous antiepileptic drug (AED) treatment. ADHD medication initiation and repeated medication periods were identified from the Swedish Prescribed Drug Register between January 1, 2006 and December 31, 2013. Acute seizures were identified via unplanned visits to hospital or specialist care with a primary seizure discharge diagnosis in the Swedish National Patient Register during the same period. Conditional Poisson regression was used to compare the seizure rate during the 24 weeks before and after initiation of ADHD medication with the rate during the same 48 weeks in the previous year. Cox regression was used to compare the seizure rate during ADHD medication periods with the rate during nonmedication periods. Comparisons were made within-individual to adjust for unmeasured, time?constant confounding.
RESULTS: Among 995 individuals who initiated ADHD medication during follow-up, within-individual analyses showed no statistically significant difference in the rate of seizures during the 24 weeks before and after medication initiation, compared to the same period in the previous year. In the full study population 11 754 seizure events occurred during 136 846 person-years and 1855 individuals had at least one ADHD medication period. ADHD medication periods were associated with a reduced rate of acute seizures (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.57-0.94), compared to nonmedication periods within the same individual. Similar associations were found in youth with epilepsy and continuous AED treatment, when adjusting for AEDs, and across sex, age, and comorbid neurodevelopmental disorders.
SIGNIFICANCE: We found no evidence for an overall increased rate of acute seizures associated with ADHD medication treatment among individuals with epilepsy. These results suggest that epilepsy should not automatically preclude patients from receiving ADHD medications.

PMID: 30682219 [PubMed - as supplied by publisher]

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Buspirone for the treatment of anxiety-related symptoms in Angelman syndrome: a case series.

Buspirone for the treatment of anxiety-related symptoms in Angelman syndrome: a case series.

Psychiatr Genet. 2019 Jan 23;:

Authors: Balaj K, Nowinski L, Walsh B, Mullett J, Palumbo ML, Thibert RL, McDougle CJ, Keary CJ

Abstract
OBJECTIVES: Angelman syndrome (AS) is a neurogenetic disorder associated with impaired expression of the ubiquitin-protein ligase E3A gene on chromosome 15. AS results in intellectual disability with limited expressive language, epilepsy, ataxia, sleep impairment, and problematic behavior which may include anxiety. Buspirone is a serotonin (5-HT)1A receptor partial agonist used in the treatment of anxiety disorders and may, therefore, have a treatment role for patients with AS.
METHODS: We describe three patients who were given open-label buspirone for the treatment of behaviors thought to be related to anxiety.
RESULTS: We found significant improvement in symptoms of anxiety with buspirone. Patients tolerated long-term usage of the medication.
CONCLUSION: The findings of this study suggest that buspirone may be effective for the amelioration of behaviors related to anxiety in patients with AS, and well tolerated. Limitations include the open-label nature of these treatments, the small sample size and the absence of a control group.

PMID: 30681431 [PubMed - as supplied by publisher]

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Gene mutations in paediatric epilepsies cause NMDA-pathy, and phasic and tonic GABA-pathy.

Gene mutations in paediatric epilepsies cause NMDA-pathy, and phasic and tonic GABA-pathy.

Dev Med Child Neurol. 2019 Jan 25;:

Authors: Gataullina S, Bienvenu T, Nabbout R, Huberfeld G, Dulac O

Abstract
The aim of this study was to disentangle mechanisms of epileptogenesis in monogenic epilepsies in children. We reviewed paediatric monogenic epilepsies excluding brain malformation or an inborn error of metabolism, but including the gene function whether there is loss-of-function or gain-of-function, age at gene expression when available, and associated epilepsy syndrome. Genes for which at least five patients with similar epilepsy phenotype had been reported were selected. Three mechanisms are shared by most monogenic epilepsies: (1) excess of N-methyl-d-aspartate (NMDA) transmission activation (NMDA-pathies); (2) abnormal gamma-aminobutyric acid (GABA) transmission with reduced inhibition (phasic GABA-pathies); and (3) tonic activation of extrasynaptic GABAA receptors by extracellular GABA (tonic GABA-pathies). NMDA-pathies comprise early epileptic encephalopathy with suppression-burst, neonatal/infantile benign seizures, West and Lennox-Gastaut syndromes, and encephalopathy with continuous spike waves in slow sleep, thus brief seizures with major interictal spiking. Phasic GABA-pathies comprise mostly generalized epilepsy with febrile seizures plus and Dravet syndrome, thus long-lasting seizures with mild interictal spiking. Tonic GABA-pathies cause epilepsy with myoclonic-atonic seizures and Angelman syndrome, thus major high-amplitude slow-wave activity. This pathophysiological approach to monogenic epilepsies provides diagnostic clues and helps to guide treatment strategy.

PMID: 30680721 [PubMed - as supplied by publisher]

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A novel cognitive behavioural intervention with Theory of Mind (ToM) training for children with epilepsy: protocol for a case series feasibility study.

A novel cognitive behavioural intervention with Theory of Mind (ToM) training for children with epilepsy: protocol for a case series feasibility study.

Pilot Feasibility Stud. 2019;5:12

Authors: Stewart E, Catroppa C, Lah S

Abstract
Background: Children with epilepsy have significant social impairments, yet evidence-based interventions to address these social difficulties are lacking. Emerging research has shown that social difficulties in children with epilepsy relate to underlying impairments in Theory of Mind (ToM). This paper outlines the protocol for a pilot study that will evaluate the feasibility, acceptability, and efficacy of a novel cognitive behavioural intervention with ToM training for children with epilepsy.
Methods: The intervention will be evaluated in a single-arm case series feasibility study. Ten to 12 children with common forms of epilepsy (8 to 12 years old) will be recruited to participate in 4 small group workshops, held over 4 consecutive weeks. Parents will attend a brief review at the end of each session with their child. Children will complete 4 one-to-one assessments with an investigator assessing ToM and social competence: twice at baseline (4 weeks and 1 day before the intervention), at post-intervention (last day of the intervention) and at follow-up (4 weeks post intervention). Parents will complete online questionnaires at these same 4 time points assessing ToM and social competence of their child. Parents and children will both complete a weekly measure of social competence from baseline 1 to follow-up. Following completion of the intervention, parents will complete two standardised questionnaires assessing treatment acceptability and barriers and facilitators to attendance; children will complete a single questionnaire on treatment acceptability. Information about feasibility outcomes (i.e. recruitment and retention, processing time, suitability of tasks) will be gathered by investigators during the trial. Together, outcomes will be used to refine research methods and make a decision about whether the intervention should be evaluated in a larger scale trial.
Discussion: To our knowledge, this is the first psychosocial intervention to address social competence problems in children with epilepsy. Findings will provide information about a potentially effective treatment that could improve longer term social outcomes for this group.
Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12618000974202, registered June 8 2018.

PMID: 30680226 [PubMed]

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Characterization of drug binding within the HCN1 channel pore.

Characterization of drug binding within the HCN1 channel pore.

Sci Rep. 2019 Jan 24;9(1):465

Authors: Tanguay J, Callahan KM, D'Avanzo N

Abstract
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels mediate rhythmic electrical activity of cardiac pacemaker cells, and in neurons play important roles in setting resting membrane potentials, dendritic integration, neuronal pacemaking, and establishing action potential threshold. Block of HCN channels slows the heart rate and is currently used to treat angina. However, HCN block also provides a promising approach to the treatment of neuronal disorders including epilepsy and neuropathic pain. While several molecules that block HCN channels have been identified, including clonidine and its derivative alinidine, lidocaine, mepivacaine, bupivacaine, ZD7288, ivabradine, zatebradine, and cilobradine, their low affinity and lack of specificity prevents wide-spread use. Different studies suggest that the binding sites of these inhibitors are located in the inner vestibule of HCN channels, but the molecular details of their binding remain unknown. We used computational docking experiments to assess the binding sites and mode of binding of these inhibitors against the recently solved atomic structure of human HCN1 channels, and a homology model of the open pore derived from a closely related CNG channel. We identify a possible hydrophobic groove in the pore cavity that plays an important role in conformationally restricting the location and orientation of drugs bound to the inner vestibule. Our results also help explain the molecular basis of the low-affinity binding of these inhibitors, paving the way for the development of higher affinity molecules.

PMID: 30679654 [PubMed - in process]

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Investigating adults with early-onset epilepsy and intellectual or physical disability.

Investigating adults with early-onset epilepsy and intellectual or physical disability.

Pract Neurol. 2019 Jan 24;:

Authors: Nashef L, Singh R, Moran N, Murphy E

Abstract
This article focuses on investigating adults with early-onset epilepsy and intellectual or physical disability within adult neurology services. We aim to guide general neurologists in the diagnostic reassessment of people with epilepsy and complex neurological problems of unknown cause. Following an overview, we address imaging, electroencephalography, genetic studies and metabolic testing, and give examples where diagnosis directly influences treatment. Aetiological diagnosis serves to inform prognosis, guide treatment and provide a framework for genetic counselling.

PMID: 30679263 [PubMed - as supplied by publisher]

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FDG-PET and MRI in the Evolution of New-Onset Refractory Status Epilepticus.

FDG-PET and MRI in the Evolution of New-Onset Refractory Status Epilepticus.

AJNR Am J Neuroradiol. 2019 Jan 24;:

Authors: Strohm T, Steriade C, Wu G, Hantus S, Rae-Grant A, Larvie M

Abstract
BACKGROUND AND PURPOSE: New-onset refractory status epilepticus is a clinical condition characterized by acute and prolonged pharmacoresistant seizures without a pre-existing relevant neurologic disorder, prior epilepsy, or clear structural, toxic, or metabolic cause. New-onset refractory status epilepticus is often associated with antineuronal antibodies and may respond to early immunosuppressive therapy, reflecting an inflammatory element of the condition. FDG-PET is a useful diagnostic tool in inflammatory and noninflammatory encephalitis. We report here FDG-PET findings in new-onset refractory status epilepticus and their correlation to disease activity, other imaging findings, and outcomes.
MATERIALS AND METHODS: Twelve patients who met the criteria for new-onset refractory status epilepticus and who had FDG-PET and MR imaging scans and electroencephalography at a single academic medical center between 2008 and 2017 were retrospectively identified. Images were independently reviewed by 2 radiologists specialized in nuclear imaging. Clinical characteristics and outcome measures were collected through chart review.
RESULTS: Twelve patients underwent 21 FDG-PET scans and 50 MR imaging scans. Nine (75%) patients were positive for autoantibodies. All patients had identifiable abnormalities on the initial FDG-PET in the form of hypermetabolism (83%) and/or hypometabolism (42%). Eight (67%) had medial temporal involvement. All patients (n = 3) with N-methyl-D-aspartic acid receptor antibodies had profound bilateral occipital hypometabolism. Initial MR imaging findings were normal in 6 (50%) patients. Most patients had some degree of persistent hyper- (73%) or hypometabolism (45%) after immunosuppressive therapy. FDG-PET hypometabolism was predictive of poor outcome (mRS 4-6) at hospital discharge (P = .028).
CONCLUSIONS: Both FDG-PET hypometabolism and hypermetabolism are seen in the setting of new-onset refractory status epilepticus and may represent markers of disease activity.

PMID: 30679215 [PubMed - as supplied by publisher]

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Management of pneumatosis intestinalis in children over the age of 6 months: a conservative approach.

Management of pneumatosis intestinalis in children over the age of 6 months: a conservative approach.

Arch Dis Child. 2018 04;103(4):352-355

Authors: Nellihela L, Mutalib M, Thompson D, Jochen K, Upadhyaya M

Abstract
BACKGROUND: Pneumatosis intestinalis (PI) is an uncommon and poorly understood condition. Although it can be an incidental finding in asymptomatic individuals, it can also be secondary to life-threatening bowel ischaemia and sepsis. In premature infants, it is a pathognomonic sign of necrotising enterocolitis. There is no consensus regarding management and long-term outcome of children with PI.
AIM: Review of our experience of PI in children beyond the early infantile period.
METHODS: Retrospective review of patient's records and radiological images from 2013 to 2015.
RESULTS: Eighteen patients (three girls) had radiologically confirmed PI. The median age was 4.5 years (range 8 months-13 years). Background medical conditions (number): short bowel syndrome (one), congenital heart disease (two), sickle cell disease (one), epilepsy (three), cerebral palsy (six), myotonic dystrophy (four) and peroxisomal biogenesis defect (one).Six children (33%) presented with abdominal distension, four (22%) with abdominal pain, three (17%) with bilious vomiting, two (11%) with diarrhoea and one (6%) with rectal bleeding. Two (11%) were asymptomatic. One had air in portal vein and two had pneumoperitoneum.All patients with symptomatic PI were treated conservatively with successful outcome and complete resolution of PI. None required surgical intervention.
CONCLUSION: PI in children who are not on chemotherapy or immunosuppressant appears to follow a benign course and is responsive to conservative management. In contrast to adults, portal venous gas and pneumoperitoneum do not predict the need for surgical intervention.

PMID: 28988213 [PubMed - indexed for MEDLINE]

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Future Oncology; +36 new citations

36 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

Future Oncology

These pubmed results were generated on 2019/01/27

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The HMG box transcription factor HBP1: a cell cycle inhibitor at the crossroads of cancer signaling pathways.

The HMG box transcription factor HBP1: a cell cycle inhibitor at the crossroads of cancer signaling pathways.

Cell Mol Life Sci. 2019 Jan 25;:

Authors: Bollaert E, de Rocca Serra A, Demoulin JB

Abstract
HMG box protein 1 (HBP1) is a transcription factor and a potent cell cycle inhibitor in normal and cancer cells. HBP1 activates or represses the expression of different cell cycle genes (such as CDKN2A, CDKN1A, and CCND1) through direct DNA binding, cofactor recruitment, chromatin remodeling, or neutralization of other transcription factors. Among these are LEF1, TCF4, and MYC in the WNT/beta-catenin pathway. HBP1 also contributes to oncogenic RAS-induced senescence and terminal cell differentiation. Collectively, these activities suggest a tumor suppressor function. However, HBP1 is not listed among frequently mutated cancer driver genes. Nevertheless, HBP1 expression is lower in several tumor types relative to matched normal tissues. Several micro-RNAs, such as miR-155, miR-17-92, and miR-29a, dampen HBP1 expression in cancer cells of various origins. The phosphatidylinositol-3 kinase (PI3K)/AKT pathway also inhibits HBP1 transcription by preventing FOXO binding to the HBP1 promoter. In addition, AKT directly phosphorylates HBP1, thereby inhibiting its transcriptional activity. Taken together, these findings place HBP1 at the center of a network of micro-RNAs and oncoproteins that control cell proliferation. In this review, we discuss our current understanding of HBP1 function in human physiology and diseases.

PMID: 30683982 [PubMed - as supplied by publisher]

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Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells.

Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells.

Nutrients. 2019 Jan 24;11(2):

Authors: Sang Eun H, Seong Min K, Ho Jeong L, Vetrivel P, Venkatarame Gowda Saralamma V, Jeong Doo H, Eun Hee K, Sang Joon L, Gon Sup K

Abstract
Scutellarein (SCU), a flavone found in the perennial herb Scutellaria baicalensis, is known for a wide range of biological activities. In the present study, we investigated the effects of treatment with SCU flavonoids on inducing apoptosis via the extrinsic pathway in Hep3B cells. SCU treatment significantly inhibited Hep3B cell proliferation and induced G2/M phase cell cycle arrest by inhibiting the expression levels of the proteins Cdc25C, cdk1 and Cyclin B1. Allophycocyanin (APC)/Annexin V and propidium iodide (PI) double-staining showed upregulation of apoptotic cell death fraction. We further confirmed apoptosis by 4'-6-diamidino-2-phenylindole (DAPI) fluorescent staining and observed DNA fragmentation with agarose gel electrophoresis. Further, immunoblotting results showed that treatment with SCU showed no changes in Bax and Bcl-xL protein levels. In addition, SCU treatment did not affect the mitochondrial membrane potential in Hep3B cells. On the contrary, treatment with SCU increased the expression of Fas and Fas ligand (FasL), which activated cleaved caspase-8, caspase-3, and polymeric adenosine diphosphate ribose (PARP), whereas the expression level of death receptor 4 (DR4) decreased. We confirmed that the proteins expressed upon treatment with SCU were involved in the Fas-mediated pathway of apoptosis in Hep3B cells. Thus, our findings in the current study strongly imply that SCU can be a basic natural source for developing potent anti-cancer agents for hepatocellular carcinoma (HCC) treatment.

PMID: 30682875 [PubMed - in process]

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Design, synthesis and biological evaluation of certain CDK2 inhibitors based on pyrazole and pyrazolo[1,5-a] pyrimidine scaffold with apoptotic activity.

Design, synthesis and biological evaluation of certain CDK2 inhibitors based on pyrazole and pyrazolo[1,5-a] pyrimidine scaffold with apoptotic activity.

Bioorg Chem. 2019 Jan 17;86:1-14

Authors: Ali GME, Ibrahim DA, Elmetwali AM, Ismail NSM

Abstract
Different series of novel pyrazole and pyrazolo[1,5-a] pyrimidine derivatives (2a-g), (3a-c), (7a-d) and (10a-e) were designed, synthesized and evaluated for their ability to inhibit CDK2/cyclin A2 enzyme in vitro. In addition, the cytotoxicity of the newly synthesized compounds was screened against four different human cancer cell lines. The CDK2/cyclin A2 enzyme inhibitory activity revealed that compounds (2d) and (2 g) are among the most active with inhibitory activity values of 60% and 40%, respectively, while compounds (7d) and (10b) exhibited the highest activity among the newly synthesized derivatives against four tumor cell lines (HepG2, MCF-7, A549 and Caco2) with IC50 values 24.24, 14.12, 30.03 and 29.27 μM and 17.12, 10.05, 29.95 and 25.24 μM, respectively. Flow cytometry cell cycle assay was carried for compounds (7d) and (10b) to investigate their apoptotic activity. The obtained results revealed that they induced cell-cycle arrest in the G0-G1phase and reinforced apoptotic DNA fragmentation. Molecular modeling studies have been carried out to gain further understanding the binding mode of the target compounds together with field alignment to define the similar field properties.

PMID: 30682722 [PubMed - as supplied by publisher]

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Phillygenin Exerts In Vitro and In Vivo Antitumor Effects in Drug-Resistant Human Esophageal Cancer Cells by Inducing Mitochondrial-Mediated Apoptosis, ROS Generation, and Inhibition of the Nuclear Factor kappa B NF-κB Signalling Pathway.

Phillygenin Exerts In Vitro and In Vivo Antitumor Effects in Drug-Resistant Human Esophageal Cancer Cells by Inducing Mitochondrial-Mediated Apoptosis, ROS Generation, and Inhibition of the Nuclear Factor kappa B NF-κB Signalling Pathway.

Med Sci Monit. 2019 Jan 25;25:739-745

Authors: He J, Wei W, Yang Q, Wang Y

Abstract
BACKGROUND Esophageal cancer causes considerable mortality and is ranked as the 6th most prevalent type of cancer across the world. At present, there is no effective esophageal cancer chemotherapy without adverse effects. Moreover, emergence of drug resistance among cancer is another obstacle in the treatment of esophageal cancer. Novel molecules of plant origin may prove beneficial in the development of chemotherapy for esophageal carcinoma. In this study we examined the anticancer effects of phillygenin against the vindesine-resistant esophageal cancer cell line SH-1-V1. MATERIAL AND METHODS The proliferation rate of SH-1-V1 cells was determined by WST-1 assay. Apoptosis was confirmed by propidium iodide (PI) staining. Cell cycle analysis, ROS, and MMP determination were performed by flow cytometery. Protein expression was assessed by Western blot analysis. RESULTS We found that phillygenin inhibited the growth of SH-1-V1 cells and exhibited an IC50 of 6 µM. Investigation of the underlying mechanism revealed that phillygenin triggered apoptotic cell death of the SH-1-V1 cells, which was also associated with enhancement of Bax expression and decreased expression of Bcl-2. Moreover, the expression of cleaved caspase 3 and 9 also increased upon phillygenin treatment. Phillygenin also caused a significant increase in ROS production, concomitant with decreased MMP levels. Phillygenin also caused arrest of cells in the G2/M phase of the cell cycle. In vivo evaluation of phillygenin revealed that it can inhibit tumor weight and volume, suggesting the anticancer potential of phillygenin. CONCLUSIONS In brief, phillygenin inhibited in vitro and in vivo cancer cell growth in drug-resistant human esophageal cancer cells, and these effects were mediated via apoptosis, ROS generation, mitochondrial membrane potential loss, and activation of the NF-kB signalling pathway.

PMID: 30681987 [PubMed - in process]

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Internal enhancement of DNA damage by a novel bispecific antibody-drug conjugate-like therapeutics via blockage of mTOR and PD-L1 signal pathways in pancreatic cancer.

Internal enhancement of DNA damage by a novel bispecific antibody-drug conjugate-like therapeutics via blockage of mTOR and PD-L1 signal pathways in pancreatic cancer.

Cancer Med. 2019 Jan 25;:

Authors: Cao R, Song W, Ye C, Liu X, Li L, Li Y, Yao H, Zhou X, Li L, Shao R

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a refractory malignant tumor with poor prognosis, limited chemotherapeutic efficacy, and only about 5% of 5-year survival rate. We generated a dual-targeting ligand-based lidamycin (DTLL) to investigate its efficacy against pancreatic cancer after preparing its precursor, DTLP. DTLP was shown specifically binding to EGFR and HER2 on cell surface, followed by endocytosis into cytoplasm of pancreatic cancer cells. DTLL significantly promoted apoptosis and cell cycle arrest at G2/M stages and inhibited cell proliferation. Pancreatic tumors of either MIA-paca-2 cell line-derived (CDX) or patient-derived xenograft (PDX) mouse models were significantly regressed in response to DTLL. It suggested that DTLL might be a highly potent bispecific antibody-drug conjugate (ADC)-like agent for pancreatic cancer therapy. LDM is known to function as an antitumor cytotoxic agent by its induction of DNA damage in cancer cells, therefore, DTLL, as its derivative, also showed similar cytotoxicity. However, we found that DTLL might reverse the AKT/mTOR feedback activation induced by LDM at the first time. The results from both in vitro and in vivo experiments suggested that DTLL enhanced DNA damage via EGFR/HER2-dependent blockage of PI3K/AKT/mTOR and PD-L1 signaling pathways in cancer cells, leading to the inhibition of cell proliferation and immunosurveillance escape from pancreatic tumor. Our studies on DTLL functional characterization revealed its novel mechanisms on internal enhancement of DNA damage and implied that DTLL might provide a promising targeted therapeutic strategy for pancreatic cancer.

PMID: 30681288 [PubMed - as supplied by publisher]

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Physicochemical property, antioxidant activity, and cytoprotective effect of the germinated soybean proteins.

Physicochemical property, antioxidant activity, and cytoprotective effect of the germinated soybean proteins.

Food Sci Nutr. 2019 Jan;7(1):120-131

Authors: Gao C, Wang F, Yuan L, Liu J, Sun D, Li X

Abstract
Appropriate germination can improve the nutritional value and bioactivity of soybeans; however, few studies have assessed the effect of germination on soybean proteins. This study examined the physicochemical property, antioxidation, and cytoprotective effect of the germinated soybean proteins (Gsp). Gsp was extracted from soybeans which germinated for 0-3 days using the method of alkali-solution and acid-isolation extraction. The results showed that germination could digest soybean proteins into the smaller molecules; enhance the degree of hydrolysis, emulsifiability, and foaming capacity; increase the removal rate of ABTS, DPPH, O 2 - ˙, and ˙OH radical; and decrease the reducing power and lipid peroxidation of Gsp. Additionally, Gsp was able to protect HL-7702 human hepatocyte cells against benzo(a)pyrene (BaP)-induced cytotoxicity through mediating the cell cycle arrest, suppressing apoptosis, and increasing reactive oxygen species (ROS) levels. This work demonstrated that germination could enhance the physicochemical property and antioxidant activity of Gsp, which also displayed the remarkable cytoprotective effect. This study provided a fundamental basis for substantiating dietary of Gsp used for resistance to oxidation and hepatic injury.

PMID: 30680165 [PubMed]

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Physical plasma-treated saline promotes an immunogenic phenotype in CT26 colon cancer cells in vitro and in vivo.

Physical plasma-treated saline promotes an immunogenic phenotype in CT26 colon cancer cells in vitro and in vivo.

Sci Rep. 2019 Jan 24;9(1):634

Authors: Freund E, Liedtke KR, van der Linde J, Metelmann HR, Heidecke CD, Partecke LI, Bekeschus S

Abstract
Metastatic colorectal cancer is the fourth most common cause of cancer death. Current options in palliation such as hyperthermic intraperitoneal chemotherapy (HIPEC) present severe side effects. Recent research efforts suggested the therapeutic use of oxidant-enriched liquid using cold physical plasma. To investigate a clinically accepted treatment regimen, we assessed the antitumor capacity of plasma-treated saline solution. In response to such liquid, CT26 murine colon cancer cells were readily oxidized and showed cell growth with subsequent apoptosis, cell cycle arrest, and upregulation of immunogenic cell death (ICD) markers in vitro. This was accompanied by marked morphological changes with re-arrangement of actin fibers and reduced motility. Induction of an epithelial-to-mesenchymal transition phenotype was not observed. Key results were confirmed in MC38 colon and PDA6606 pancreatic cancer cells. Compared to plasma-treated saline, hydrogen peroxide was inferiorly toxic in 3D tumor spheroids but of similar efficacy in 2D models. In vivo, plasma-treated saline decreased tumor burden in Balb/C mice. This was concomitant with elevated numbers of intratumoral macrophages and increased T cell activation following incubation with CT26 cells ex vivo. Being a potential adjuvant for HIPEC therapy, our results suggest oxidizing saline solutions to inactivate colon cancer cells while potentially stimulating antitumor immune responses.

PMID: 30679720 [PubMed - in process]

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Off-target based drug repurposing opportunities for tivantinib in acute myeloid leukemia.

Off-target based drug repurposing opportunities for tivantinib in acute myeloid leukemia.

Sci Rep. 2019 Jan 24;9(1):606

Authors: Kuenzi BM, Remsing Rix LL, Kinose F, Kroeger JL, Lancet JE, Padron E, Rix U

Abstract
GSK3α has been identified as a new target in the treatment of acute myeloid leukemia (AML). However, most GSK3 inhibitors lack specificity for GSK3α over GSK3β and other kinases. We have previously shown in lung cancer cells that GSK3α and to a lesser extent GSK3β are inhibited by the advanced clinical candidate tivantinib (ARQ197), which was designed as a MET inhibitor. Thus, we hypothesized that tivantinib would be an effective therapy for the treatment of AML. Here, we show that tivantinib has potent anticancer activity across several AML cell lines and primary patient cells. Tivantinib strongly induced apoptosis, differentiation and G2/M cell cycle arrest and caused less undesirable stabilization of β-catenin compared to the pan-GSK3 inhibitor LiCl. Subsequent drug combination studies identified the BCL-2 inhibitor ABT-199 to synergize with tivantinib while cytarabine combination with tivantinib was antagonistic. Interestingly, the addition of ABT-199 to tivantinib completely abrogated tivantinib induced β-catenin stabilization. Tivantinib alone, or in combination with ABT-199, downregulated anti-apoptotic MCL-1 and BCL-XL levels, which likely contribute to the observed synergy. Importantly, tivantinib as single agent or in combination with ABT-199 significantly inhibited the colony forming capacity of primary patient AML bone marrow mononuclear cells. In summary, tivantinib is a novel GSK3α/β inhibitor that potently kills AML cells and tivantinib single agent or combination therapy with ABT-199 may represent attractive new therapeutic opportunities for AML.

PMID: 30679640 [PubMed - in process]

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Huaier n-butanol extract suppresses proliferation and metastasis of gastric cancer via c-Myc-Bmi1 axis.

Huaier n-butanol extract suppresses proliferation and metastasis of gastric cancer via c-Myc-Bmi1 axis.

Sci Rep. 2019 Jan 24;9(1):447

Authors: Wang Y, Lv H, Xu Z, Sun J, Ni Y, Chen Z, Cheng X

Abstract
Gastric cancer (GC) ranks as the third leading cause of cancer-related mortality worldwide, and approximately 42% of all cases diagnosed each year worldwide are diagnosed in China. A large number of clinical applications have revealed that Trametes robiniophila Μurr. (Huaier) exhibits an anti-tumour effect. However, loss of the bioactive components of Huaier during the extraction procedure with water is unavoidable, and the underlying mechanism of the anti-cancer effect of Huaier remains poorly understood. In this study, we investigated the anti-cancer effect of Huaier n-butanol extract, which contained 51.4% total flavonoids, on HGC27, MGC803, and AGS human GC cell lines in vitro. At a low concentration, Huaier n-butanol extract inhibited the growth of these GC cell types, induced cell cycle arrest and reduced cell metastasis. Moreover, Huaier n-butanol extract suppressed the c-Myc-Bmi1 signalling pathway, and overexpression of Bmi1 reversed the effects of Huaier n-butanol extract on GC cells. Thus, our findings indicate that Huaier n-butanol extract suppresses the proliferation and metastasis of GC cells via a c-Myc-Bmi1-mediated approach, providing a new perspective for our understanding of the anti-tumour effects of Huaier. These results suggest that Huaier n-butanol extract could be an attractive therapeutic adjuvant for the treatment of human GC.

PMID: 30679589 [PubMed - in process]

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Κυριακή 27 Ιανουαρίου 2019

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