A randomized phase III double-blind placebo-controlled trial of first-line chemotherapy and trastuzumab with or without bevacizumab for patients with HER2/neu-positive metastatic breast cancer: a trial of the ECOG-ACRIN Cancer Research Group (E1105).

BACKGROUND: In 2008, bevacizumab received accelerated Food and Drug Administration (FDA) approval for use in human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Based on the pre-clinical and preliminary clinical activity of the trastuzumab and bevacizumab combination, ECOG-ACRIN E1105 trial was developed to determine if the addition of bevacizumab to a chemotherapy and trastuzumab combination for first-line therapy would improve progression-free survival (PFS) in patients with HER2-positive MBC. FINDINGS: 96 patients were randomized to receive standard first-line chemotherapy and trastuzumab with or without bevacizumab between November 2007 and October 2009, and 93 began protocol therapy. Induction therapy was given for 24 weeks, followed by maintenance trastuzumab with or without bevacizumab. 60% (56/93) began carboplatin and 74% (69/93) completed 6 cycles of induction therapy. Primary endpoint was PFS. Median PFS was 11.1 and 13.8 months for placebo and bevacizumab arms, respectively (hazard ratio [HR] 95%, Confidence Interval [Cl] for bevacizumab vs. placebo: 0.73 [0.43-1.23], p = 0.24), and at a median follow-up of 70.7 months, median survival was 49.1 and 63 months (HR [95% Cl] for OS: 1.09 [0.61-1.97], p = 0.75). The most common toxicities across both arms were neutropenia and hypertension, with left ventricular systolic dysfunction, fatigue, and sensory neuropathy reported more frequently with bevacizumab. CONCLUSIONS: In this trial, the addition of bevacizumab did not improve outcomes in patients with metastatic HER2-positive breast cancer. Although the trial was underpowered due to smaller than anticipated sample size, these findings corroborated other clinical trials during this time. CLINICAL TRIAL INFORMATION: NCT00520975.

Incidental diagnosis of intestinal perforation on a 99mTc DTPA renogram.

Perforation of the bowel can be a life-threatening condition and is usually clinically diagnosed when a patient presents with such features as severe abdominal pain, tenderness, and tachycardia. Bowel perforation may be corroborated by various conventional imaging modalities, including X-ray, ultrasonography, computed tomography, and magnetic resonance imaging. Nuclear medicine imaging modalities seldom have a role to play in these settings. Rarely diagnosis of perforation may be missed if it is concealed and does not present with the usual signs. Mostly the perforation will eventually be diagnosed if they develop signs and symptoms and is taken up for an exploratory laparotomy. A delay in diagnosis can later lead to significant patient morbidity or even mortality. This report describes a case where possible intestinal perforation was suspected on a 99mTc-DTPA renogram in a postoperative patient with significant urine leak, the presence of which was confirmed intraoperatively. To our knowledge, this was the first such case in the literature.

18F-FDG PET CT in cardiac device infections - A Case series.

With the increasing number of interventional cardiology procedures, the number of cardiac device infections (including pacemakers, prosthetic valves, coronary and aortic stents) have also increased. These infections can cause significant morbidity and can even lead to mortality if not managed promptly. If suspected clinically the first-line imaging modality is Trans-Thoracic Echocardiography, while Transesophageal Echocardiography is also used in selected cases. The confirmation of a cardiac device infection is mostly done with the help of blood or pus culture. Even though Echocardiography is a very efficient technique for the evaluation of the heart, it cannot differentiate infection from thrombus or fibrosis. With the increasing availability of Positron Emission Tomography CT (PET CT) machines worldwide, the use of 18F-FDG PET CT for infection imaging has gained traction, especially for cardiac device infection. Most of the recent studies show a good diagnostic accuracy of 18F-FDG PET CT with many of the recent diagnostic and management guidelines now acknowledging its role, especially in equivocal cases. We present six such cases where 18F-FDG PET CT provided valuable information either for diagnosis, confirming the presence of infection, delineating extent, therapy response or sometimes even helping appropriate treatment decision making in patients with suspected cardiac device infection.

Non O1 non O139 Vibrio cholerae septicemia in a patient with carcinoma pancreas-a case report and literature review, 2020-2023.

Non-O1/non-O139 Vibrio cholerae, a comparably poorly studied pathogen is culpable of sporadic but serious infections. We report a case of non O1 non O139 Vibrio cholerae septicemia in a middle aged male recently diagnosed with carcinoma pancreas. He underwent biliary tract interventional procedure for hematemesis three weeks before the presentation. Now, he presented with fever, abdominal pain, hematemesis and melena. Endoscopy revealed severe portal hypertensive gastropathy and mild hemobilia. Blood culture grew Vibrio cholerae, identified as non O1 non O139 by serogrouping. He recovered successfully with timely diagnosis, appropriate antibiotics and supportive measures.

A randomized phase III double-blind placebo-controlled trial of first line chemotherapy and trastuzumab with or without bevacizumab for patients with HER2/neu-positive metastatic breast cancer: a trial of the ECOG-ACRIN Cancer Research Group (E1105).

Background: In 2008, bevacizumab received accelerated Food and Drug Administration (FDA) approval for use in human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Based on the preclinical and preliminary clinical activity of the trastuzumab and bevacizumab combination, ECOG-ACRIN E1105 trial was developed to determine if the addition of bevacizumab to a chemotherapy and trastuzumab combination for first-line therapy would improve progression-free survival (PFS) in patients with HER2-positive MBC. Findings: 96 patients were randomized to receive standard first-line chemotherapy and trastuzumab with or without bevacizumab between November 2007 and October 2009, and 93 began protocol therapy. Induction therapy was given for 24 weeks, followed by maintenance trastuzumab with or without bevacizumab. 60% (56/93) began carboplatin and 74% (69/93) completed 6 cycles of induction therapy. Primary endpoint was PFS. Median PFS was 11.1 and 13.8 months for placebo and bevacizumab arms, respectively (hazard ratio [HR] 95%, Confidence Interval [Cl] for bevacizumab vs. placebo: 0.73 [0.43-1.23], p = 0.24), and at a median follow-up of 70.7 months, median survival was 49.1 and 63 months (HR [95% Cl] for OS: 1.09 [0.61-1.97], p = 0.75). The most common toxicities across both arms were neutropenia and hypertension, with left ventricular systolic dysfunction, fatigue, and sensory neuropathy reported more frequently with bevacizumab. Conclusions: In this trial, the addition of bevacizumab did not improve outcomes in patients with metastatic HER2-positive breast cancer. Although the trial was underpowered due to smaller than anticipated sample size, these findings corroborated other clinical trials during this time.

Mycobacterium abscessus endocarditis post cardiac cathetrisation-a case report and review of 25 cases (2001-2023).

47 year male underwent percutaneous transluminal coronary angioplasty elsewhere, developed fever after two days, and treated empirically in various hospitals for the subsequent two months. Echocardiography showed vegetation in aortic valve and blood cultures were negative. He was then diagnosed as a case of endocarditis due to M. abscessus in our centre by repeated positive blood cultures. After treatment with Imipenem, Amikacin and clarithromycin in the background of pancytopenia, patient was discharged with advice to continue antibiotics and planned for aortic valve replacement. Patient was noncompliant to treatment, readmitted with worsening symptoms, developed multiorgan failure and subsequently died of infection.

Structural, Optical and Magnetic Properties of Zn1-xCoxO Nanoparticles.

Zn1-xCoxO nanoparticles with three different values of 'x' (x = 0.05, 0.10, 0.15) were prepared by chemical co-precipitation process without any further heat treatment. The X-ray diffraction studies confirmed the wurtzite hexagonal crystal structure for synthesized Zn1-xCoxO nanoparticles. The dislocation density results reveal that there is an increase in the concentration of lattice imperfections with increasing the concentration of Co ions. The true values of lattice constants were calculated by using Nelson-Riley Function (NRF). Further, the average bond length (BL) were also calculated and presented. The optical and magnetic properties of Zn1-xCoxO nanoparticles were examined by room-temperature photoluminescence (PL) spectroscopy and vibrating sample magnetometer (VSM), respectively. The calculated values of magnetic susceptibility for Zn1-xCoxO nanoparticles with x = 0.05, 0.10, 0.15 were found to be 9.883×10-4, 2.29×10-2 and 2.37×10-2, respectively.

An Enhancement of Computer Aided Approach for Colon Cancer Detection in WCE Images Using ROI Based Color Histogram and SVM2.

The colon cancer is formed by uncontrollable growth of abnormal cells in large intestine or colon that can affect both men and women and it is third cancer disease in the world. At present, Wireless Capsule Endoscopy (WCE) screening method is utilized to identify colon cancer tumor at early stage to save the patient life who affected by the colon cancer. In this CTC method, the radiologist needs to analyze the colon polyps in digital image using computer aided approach with accurate automatic tumor classification to detect the cancer tumor at early stage. This kind of computer aided approach can operate as an intermediate between input digital image and radiologist. Therefore, in this paper, a novel computer aided approach is presented with ROI based color histogram and SVM2 to find the cancer tumor in WCE image. In this method, the digital WCE image can be preprocessed using filtering and ROI based color histogram depending on the salient region in colon. In common, the salient region can be distinctive because of low redundancy. Hence, the saliency is estimated by ROI based color histogram on the basis of color and structure contrast in given colon image for the further process of clustering and tumor classification in WCE image. The K-means clustering can be employed to cluster the preprocessed digital image to discover the tumor of colon. Subsequently, the features are extracted from the image in terms of contrast, correlation, energy and homogeneity by applying SGLDM method. The SVM2 classifier as input to classify the tumor is normal or malignancy using selected feature vectors. Here, the extracted features can also being combined to enhance the hybrid feature vector for the accurate tumor classification. Experimental results of proposed method can show that this presented technique can executes can tumor detection in colon image accurately reaching almost 95% in evaluation with existing algorithms.

Dynamical resonances of the deuterated CH2+ complex in the electronic ground state: A quantum wavepacket study.

We here investigate the effects of isotopic substituents on the vibrational energy levels of the CH2+ complex, supported by the electronic ground (1 2A') potential energy surface (PES) of the H + CH+ reaction. We calculate the transition state spectrum by Fourier transforming the time-autocorrelation function of the initial wavepacket (WP) chosen in the interaction region of the PES. Using the time-dependent WP approach, the dynamical resonances are identified as bound and quasibound in nature, and they are characterized in terms of the eigenfunctions and lifetimes. The present work on the isotopic variants [CHD+(CDH+) and CD2+] is compared with our earlier work [P. Sundaram et al., Phys. Chem. Chem. Phys. 19, 20172 (2017)] on the parent CH2+ species. The isotopic variants reveal a large number of peaks in the spectra and the eigenfunctions exhibit the systematic nodal progressions and periodic orbits, the same as in CH2+. While the CD2+ complex exactly mimics the resonance behaviors (local and hyperspherical modes) of the bound and quasibound CH2+ complex, the CHD+(CDH+) complex reveals only the local mode behaviors at low energies and significantly less number of resonance structures at high energies. Lifetime analysis of the isotopic variants implies that the CD2+ complex survives much longer than the CHD+(CDH+) complex and concludes the work by noting the following order in the decay profile of the deuterated CH2+ resonances as CH2+>CHD+(CDH+) >CD2+.

Which is Better - A Standalone Ventilation or Perfusion Scan or Combined Imaging to Predict Postoperative FEV1 in One Seconds in Patients Posted for Lung Surgeries with Borderline Pulmonary Reserve.

INTRODUCTION: Forced expiratory volume in one second (FEV1) is an independent predictor for respiratory morbidity. Reports are varied and controversial substantiating the use of either lung perfusion (Q) or ventilation (V) scintigraphy as a single stage investigation to predict postoperative (ppo) FEV1 in patients scheduled for lung resection surgeries. It is said that there is no additional benefit by performing both V/Q scan. As per one of the recommendations, no further respiratory function tests are required for a lobectomy if the postbronchodilator FEV1 is >1.5 l. We wanted to study the ppo FEV1 in patients with FEV1 of <1.5 L scheduled for lung surgeries. Being a high-risk population, we wanted to assess (a) whether the ppo changes by this combined V/Q imaging and (b) whether the incidence of respiratory complication in the postoperative setting of this subgroup is different, (c) and study the short- and long-term clinical outcome. MATERIALS AND METHODS: Fifty-two high-risk patients (with comorbidities) and borderline preoperative FEV1 of 1.5 L or less planned for lung resection were enroled in this prospective study. V and Q scans were performed, and tracer uptake percentage was tabulated. RESULTS: Tracer uptake in each lung was quantitated. Manual method of ROI drawing is preferred in high risk patients with reduced pulmonary reserve over the automatic method. Based on uptake patterns by V/Q scans, 4 different types of patterns were tabulated. Eighty-eight percentage of centrally placed tumors showed the difference in uptake patterns. Chronic obstructive pulmonary disease patients usually showed more modest ventilatory defects (categorised as type 2 or 3). Lung tumours produce erratic uptake patterns (Type 4) which depend heavily on their location and extent. The range of FEV1 predicted was 0.6-1.38 L/min. CONCLUSION: We recommend that combined imaging should be performed in patients with borderline pulmonary reserve to derive the benefit of surgery as it provides a realistic ppo FEV1 in patients with moderate to severely damaged lung. Centrally placed hilar or bronchial tumors (even those <2 cm in size), produce discrepancies in V/Q distribution pattern. Patient who was thought ineligible for surgery due to low baseline FEV1 may be actually be operable by this combined imaging if uptake pattern is better in V or Q scan with a good outcome. Accurate estimation of postop FEV1 in fact helps the surgical team to implement measures to prepare high risk patients to reduce postoperative complications, enable faster weaning from ventilatory support and ensure favourable prognosis.

Dynamics and resonances of the H(2S) + CH+(X1Σ+) reaction in the electronic ground state: a detailed quantum wavepacket study.

Initial state-selected and energy resolved channel-specific reaction probabilities, integral cross sections and thermal rate constants of the H(2S) + CH+(X1Σ+) reaction are calculated within the coupled states approximation by a time-dependent wave packet propagation method. The new ab initio global potential energy surface (PES) of the electronic ground state (1 2A') of the system, recently reported by Li et al. [J. Chem. Phys., 2015, 142, 124302], is employed for this purpose. All partial wave contributions up to the total angular momentum J = 60 are considered to obtain the converged integral reaction cross section up to a collision energy of 1.0 eV. Thermal rate constants are calculated by averaging the reaction cross sections over the Boltzmann distribution of energies and compared with the available theoretical and experimental results for the temperature range 10-1000 K. Investigation of the channel-specific reaction attributes shows that the H abstraction (CH+ destruction) channel is highly favored over the H exchange channel. The effect of rotational and vibrational excitations of the CH+ reagent on the dynamics is also studied. The resonances formed during the course of the reaction are also identified by calculating the transition state spectrum and characterized in terms of the eigenfunctions and lifetimes. More than 260 vibrational levels are obtained and their eigenfunctions are calculated, which are represented in terms of the nodal assignments and the eigenenergies. They reveal both the local and hyperspherical behavior for the bound and quasibound states of the CH2+ complex in the ground 1 2A' surface. The lifetime analysis of the quasibound states indicates that the CH2+ resonances survive for as long as ∼400 fs at high energies (E ∼ 2.0 eV) and are expected to decay faster with further increasing energy. Finally, the type of mechanism for the formation of the product (C+ + H2) is elucidated.

Role of Axillary Ultrasound, Fine Needle Aspiration Cytology and Sentinel Lymph Node Biopsy in clinically N0 Breast Cancer.

This study evaluates the combined role of axillary ultrasound, fine needle aspiration cytology and sentinel lymph node biopsy in clinically N0 axilla. Between January 2014 and June 2015, 150 women with early breast cancer underwent axillary ultrasound as a first investigation for nodal status. Suspicious nodes were subjected to image guided fine needle aspiration cytology. Non-suspicious and fine needle aspiration cytology negative axillary nodes proceeded to sentinel lymph node biopsy at time of primary breast surgery. All confirmed positive (cytology and frozen) cases proceeded to axillary lymph node dissection. 52 women had positive axillary nodes at final histology. Axillary ultrasound with fine needle aspiration cytology identified 27 patients with positive axillary nodal status and had a sensitivity of 84.36 % (27/32) and specificity of 87.5 % (14/16). Intraoperative frozen analysis identified a further 13 cases with sensitivity of 56.52 % (13/23) and specificity of 97.56 % (80/82). Overall 76.92 % (40/52) patients with positive axillary metastasis were identified peri-operatively using combination of axillary ultrasound, cytology and sentinel lymph node biopsy.

Corrosion behavior of plasma electrolytically oxidized gamma titanium aluminide alloy in simulated body fluid.

Plasma electrolytic oxidized (PEO) γTiAl alloy samples were electrochemically characterized by open circuit potential (OCP), cyclic polarization and electrochemical impedance spectroscopy (EIS) to evaluate their corrosion resistance in simulated body fluid (SBF) in order to gauge their potential for biomedical applications. Experimental results through OCP and cyclic polarization studies demonstrated the protective nature and the beneficial effect of the PEO coatings on γTiAl. The PEO surface increased corrosion resistance of these surface modified alloys. EIS data indicated the presence of an underlying compact oxide layer with surface pores represented by two domes in the Nyquist plots. Electrical equivalent circuits to describe the EIS results are proposed.

Vinculin expression in MC3T3-E1 cells in response to mechanical stimulus.

Loading frequency is known to influence the expression of the focal adhesions of the adherent cells. A small cyclical tensile force was transmitted to mouse pre-osteoblast MC3T3-E1 cells through PDMS substrates of varying stiffness. Changes in cell behavior with respect to proliferation and characteristics of focal adhesions were quantified through immunofluorescence labeling of vinculin. Amount of inactive vinculin was higher on substrates subjected to cyclic stimulation when compared with the results of the static substrates, whereas the number and area of focal adhesion points underwent a reduction. Inactive vinculin appears as a cloud in the cytoplasm in the vicinity of the nucleus.

Radioiodine as an adjuvant therapy and its role in follow-up of differentiated thyroid cancer.

Papillary and follicular cancers of thyroid are the most common varieties of differentiated thyroid cancers exhibiting excellent long-term prognosis when carefully managed. Being a slow-growing malignancy, guidelines exist on the staging, preoperative risk stratification, and management of these cancers to increase the overall survival of these patients. Radioactive iodine has a central role in differentiated thyroid malignancies. It has the same physical properties as stable iodine, thus both normal and malignant thyrocytes cannot differentiate radioactive from stable iodine. Differentiated thyroid carcinoma (DTC) cells concentrate cytocidal amounts of Iodine -131 (131 I) by trapping (the function of the sodium iodine symporter, or NIS) and organifying the iodide ion to produce levothyroxine and triiodothyronine. We shall discuss the role of radioiodine in the management and followup of DTC patients.

Titanium Oxide: A Bioactive Factor in Osteoblast Differentiation.

Titanium and titanium alloys are currently accepted as the gold standard in dental applications. Their excellent biocompatibility has been attributed to the inert titanium surface through the formation of a thin native oxide which has been correlated to the excellent corrosion resistance of this material in body fluids. Whether this titanium oxide layer is essential to the outstanding biocompatibility of titanium surfaces in orthopedic biomaterial applications is still a moot point. To study this critical aspect further, human fetal osteoblasts were cultured on thermally oxidized and microarc oxidized (MAO) surfaces and cell differentiation, a key indicator in bone tissue growth, was quantified by measuring the expression of alkaline phosphatase (ALP) using a commercial assay kit. Cell attachment was similar on all the oxidized surfaces although ALP expression was highest on the oxidized titanium alloy surfaces. Untreated titanium alloy surfaces showed a distinctly lower degree of ALP activity. This indicates that titanium oxide clearly upregulates ALP expression in human fetal osteoblasts and may be a key bioactive factor that causes the excellent biocompatibility of titanium alloys. This result may make it imperative to incorporate titanium oxide in all hard tissue applications involving titanium and other alloys.

Electrochemical characterization of MC3T3-E1 cells cultured on γTiAl and Ti-6Al-4V alloys.

Electrochemical impedance spectroscopy (EIS) was used to study the behavior of MC3T3-E1 cells cultured in an αMEM+FBS solution on two Ti-based alloys (Ti-6Al-4V and γTiAl) for 4, 7 and 14 days. EIS measurements were carried out at an open-circuit potential in a 1 mHz to 100 kHz frequency range. Results indicate a general increase in impedance on the Ti alloy surfaces with cells as a function of time. Bode plots indicate changes corresponding to the passive oxide film, adsorption of proteins and cell tissue on surfaces with the passage of time. Normal cellular activity based on the polygonal morphology, with long and fine cytoplasmic prolongations of the cells on Ti-6Al-4V and γTiAl was observed from SEM images. Similarly, mineralization nodules corresponding to cell differentiation associated with the osseogenetic process were observed confirmed by Alizarin Red S staining. Immunofluorescence analysis to detect the presence of collagen Type I showed an increase in the segregation of collagen as a function of time. The impedance values obtained from EIS testing are indicative of the corrosion protection offered to the Ti alloy substrates by the cell layer. This study shows that γTiAl has better corrosion resistance than that of Ti-6Al-4V in the αMEM+FBS environment in the presence of MC3T3-E1 cells.

Primary peripheral neurolymphomatosis mimicking synovial sarcoma: FDG PETCT to the rescue.

Our understanding of the association between synovial sarcoma and peripheral neurolymphomatosis is limited to a few case reports in literature. Delay in diagnosis or misdiagnosis is possible due to its insidious onset and varied presentation compounded by non-specific imaging findings. Needle biopsy also may not be confirmatory especially, in cases of biphasic sarcoma as in our case, and it may be necessary to proceed to open biopsy. Here, is a case of a non-tender right calf muscle mass, which was reported as biphasic synovial sarcoma by FNAC. Positron emission tomography computed tomography-computed tomography (PETCT) showed right sciatic nerve involvement and multiple infra diaphragmatic lymph nodal lesions. Intensity of (18)F FDG ((18)Flourine labeled fluro de oxy glucose) uptake and the infra diaphragmatic lymph nodal lesions distribution, was more in favour of a lymphoma diagnosis rather than a sarcoma, (which are usually low metabolically active tumors). Thus, this case highlights the usefulness of FDG PETCT in arriving at a diagnosis in the background of indeterminate clinicopathological and radiologic findings.

Current practice and recommendation for presurgical cardiac evaluation in patients undergoing noncardiac surgeries.

The increasing number of patients with coronary artery disease (CAD) undergoing major noncardiac surgery justifies guidelines concerning preoperative cardiac evaluation. This is compounded by increasing chances for a volatile perioperative period if the underlying cardiac problems are left uncorrected prior to major noncardiac surgeries. Preoperative cardiac evaluation requires the clinician to assess the patient's probability to have CAD, severity and stability of CAD, placing these in perspective regarding the likelihood of a perioperative cardiac complication based on the planned surgical procedure. Coronary events like new onset ischemia, infarction, or revascularization, induce a high-risk period of 6 weeks, and an intermediate-risk period of 3 months before performing noncardiac surgery. This delay is unwarranted in cases where surgery is the mainstay of treatment. The objective of this review is to offer a comprehensive algorithm in the preoperative assessment of patients undergoing noncardiac surgery and highlight the importance of myocardial perfusion imaging in risk stratifying these patients.