Development of a novel CT-based index for predicting the number of extracorporeal shockwave lithotripsy (ESWL) sessions required for successful fragmentation of obstructing pancreatic duct stones.

BACKGROUND & AIM: Extracorporeal shock wave lithotripsy (ESWL) is used for the treatment of pancreatic duct stones (PDS) in patients with chronic pancreatitis (CP). We aimed to develop a CT based index to predict the required number of ESWL sessions for technical success. METHODS: We retrospectively evaluated patients with PDS secondary to CP who underwent ESWL. Technical success was defined as the complete fragmentation of stones to <3 mm. CT features including PDS size, number, location, and density in Hounsfield units (HU) were noted. We analyzed the relationship between PDS characteristics and the number of ESWL sessions required for technical success. A multiple linear regression model was used to combine size and density into the pancreatic duct stone (PDS) index that was translated into a web-based calculator. RESULTS: There were 206 subjects (mean age 38.6 ± 13.7 years, 59.2% male) who underwent ESWL. PDS size showed a moderate correlation with the number of ESWL sessions (r = 0.42, p < 0.01). PDS in the head required a fewer number of sessions in comparison to those in the body (1.4 ± 0.6 vs. 1.6 ± 0.7, p = 0.01). There was a strong correlation between PDS density and the number of ESWL sessions (r = 0.617, p-value <0.01). The PDS index {0.3793 + [0.0009755 x PDS density (HU)] + [0.02549 x PDS size (mm)]} could accurately predict the required number of ESWL sessions with an AUC of 0.872 (p < 0.01). CONCLUSION: The PDS index is a useful predictor of the number of ESWL sessions needed for technical success that can help in planning and patient counseling.

Cadaveric Study of Colon Lengthening Maneuvers Following Sigmoidectomy.

BACKGROUND: Creation of a tension free colorectal anastomosis after left colon resection or low anterior resection is a key requirement for technical success. The relative contribution of each of a series of known lengthening maneuvers remains incompletely characterized. OBJECTIVE: The aim of this study was to compare technical procedures for lengthening of the left colon prior to rectal anastomosis. DESIGN: A series of lengthening maneuvers was performed on 15 fresh cadavers. Average distance gained was measured for each successive maneuver, including (1) high inferior mesenteric artery ligation, (2) splenic flexure takedown, and (3) high inferior mesenteric vein ligation by the ligament of Treitz. SETTING: Cadaveric study. MAIN OUTCOME MEASURES: The pre-mobilization and post-mobilization position of the proximal colonic end was measured relative to the inferior edge of the sacral promontory. Measurements of the colonic length relative to the sacral promontory were taken following each mobilization maneuver. The inferior mesenteric artery, sigmoid colon and rectum specimen lengths were measured. The distance from the inferior border of the sacral promontory to the pelvic floor was measured along the sacral curvature. RESULTS: Average sigmoid colon resection length was 34.7 ± 11.1 cm. Prior to any lengthening, baseline reach was -1.3 ± 4.2 cm from the sacral promontory. Inferior mesenteric artery ligation yielded an additional 11.5 ± 4.7 cm. Subsequent splenic flexure takedown added an additional 12.8 ± 9.6 cm. Finally, inferior mesenteric vein ligation added an additional 11.33 ± 6.9 cm, bringing the total colonic length to 35.7 ± 14.7 cm. BMI and weight negatively correlated with length gained. LIMITATIONS: The study was limited by nature of being a cadaver study. CONCLUSIONS: Stepwise lengthening maneuvers allow significant additional reach to allow a tension free left colon to rectal anastomosis. See Video Abstract.

Complete mesocolic excision and extended lymphadenectomy: Where should we stand?

Debate regarding the risks and merits of complete mesocolic excision and extended lymphadenectomy is ongoing, particularly for right-sided colon cancers. In this article, we hope to provide a succinct yet encompassing review of the relevant literature. We posit that complete mesocolic excision with D3 dissection is indicated in select patients with colon cancers, particularly those distal to the cecum.

Efficacy of Triglyceride Glucose Index-Neck Circumference and Triglyceride Glucose Index-Neck-to-Height Ratio in the Diagnosis of Cardiovascular Diseases and Metabolic Syndrome.

BACKGROUND: A group of characteristics known as metabolic syndrome raises the chance of developing diabetes and cardiovascular disease. Insulin resistance (IR) and obesity are regarded as critical metabolic syndrome pathophysiology. OBJECTIVES: The diagnostic accuracy of IR indicators, triglyceride (TG) glucose index-neck circumference (TyG-NC), and TG glucose index-neck-to-height ratio (TyG-NHtR) to be evaluated for the detection of cardiovascular diseases and metabolic syndrome in nondiabetic individuals. MATERIALS AND METHODS: A cross-sectional study was conducted and passed by the Ethics Committee of the institute. The age should be 18 years or older, and subjects should not have diabetes. Each patient's clinical information was gathered, and lab tests were run. The study was done for a period of 1 year. RESULTS: The study has 100 participants. Around 74% of the group was women. Only 26.5% of the group had an obesity diagnosis. Poor fasting plasma glucose levels were found in 19.4% of the research team. Receiver operating characteristic (ROC)-area under the curve (AUC) testing revealed that all examined IR indices can differentiate individuals with metabolic syndrome from those who are healthy. Our analysis laid out the soaring high area under the ROC curve for TyG index and the low stunted area under the ROC curve for TyG-NC. For obesity, all indices showed appreciable diagnostic efficacy, indicating the maximum achieved area under the ROC curve for TyG index and the minimum recorded metabolic score for IR. The AUC in the case of the metabolic score for IR (METS-IR) male sample population was found to be not statistically compelling. CONCLUSION: The exploration of indirect indices, the proposed ones, namely TyG-NC and TyG-NHtR, emphasized an intricate link between cardiovascular diseases and metabolic syndrome.

Probing the general base for DNA polymerization in telomerase: a molecular dynamics investigation.

Telomerase is an RNA-dependent DNA polymerase that plays a role in the maintenance of the 3' end of the eukaryotic chromosome, known as a telomere, by catalyzing the DNA polymerization reaction in cancer and embryonic stem cells. The detailed molecular details of the DNA polymerization by telomerase, especially the general base for deprotonating the terminal 3'-hydroxyl, which triggers the chemical reaction, remain elusive. We conducted a computational investigation using hybrid quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations to probe the detailed mechanism of the reaction. Our simulations started with the telomerase:RNA:DNA:dNTP ternary complex, and by using enhanced sampling QM/MM MD simulations, we probed the general base involved directly in the polymerization. We report the participation of an aspartate (Asp344) coordinated to Mg and an active site water molecule, jointly acting as a base during nucleic acid addition. The Asp344 residue remains transiently protonated during the course of the reaction, and later it deprotonates by transferring its proton to the water at the end of the reaction.

Increased cost burden associated with robot-assisted rectopexy: do patient outcomes justify increased expenditure?

BACKGROUND: Robot-assisted surgical techniques have flourished over the years, with refinement in instrumentation and optics allowing for adaptation and increasing utilization across surgical fields. Transabdominal rectopexy with mesh for rectal prolapse may stand to benefit significantly from the use of a robotic platform. However, increased operative times and immediate associated costs of robotic surgery may provide a counterargument to widespread adoption. METHODS: To determine which approach to the treatment of rectal prolapse, laparoscopic or robotic, is more cost effective and provides better outcomes with fewer complications, a retrospective review was performed at a single tertiary care academic institution from May 2013 to December 2020. Twenty-two patients underwent transabdominal mesh rectopexy through a robot-assisted DaVinci platform (Intuitive Sunnyvale, CA), and thirty through a laparoscopic platform. Main outcome measures included operative, hospital, and total cost as defined by total charges billed. Secondary outcomes included rate of recurrence, intra-operative complications, median operative time, post-operative complications, average hospital length of stay, inpatient pain medication usage, and post-operative functional outcomes. RESULTS: Cost analysis for robot-assisted versus laparoscopic rectopexy demonstrated operating room costs of $46,118 ± $9329 for the robotic group, versus $33,090 ± $15,395 (p = 0.002) for the laparoscopic group. Inpatient hospital costs were $60,723 ± $20,170 vs. $40,798 ± $14,325 (p = 0.001), and total costs were $106,841 ± $25,513 vs. $73,888 ± $28,129 (p ≤ 0.001). When secondary outcomes were compared for the robotic versus laparoscopic groups, there were no differences in any of the aforementioned outcome variables except for operative time, which was 79 min longer in the robotic group (p ≤ 0.001). CONCLUSIONS: Robot-assisted mesh rectopexy demonstrated no clinical benefit over traditional laparoscopic mesh rectopexy, with significantly higher operative and hospital costs. A reduction in the acquisition and maintenance costs for robotic surgery is needed before large-scale adoption and implementation of the robotic platform for this procedure.

Expression unleashed in artificial intelligence.

The problem of generating generally capable agents is an important frontier in artificial intelligence (AI) research. Such agents may demonstrate open-ended, versatile, and diverse modes of expression, similar to humans. We interpret the work of Heintz & Scott-Phillips as a minimal sufficient set of socio-cognitive biases for the emergence of generally expressive AI, separate yet complementary to existing algorithms.

Incidence of New-onset Hypertension and New-onset Type 2 Diabetes during or after SARS-CoV-2 Infection.

Background: Considering the potential clinical and therapeutic implications, there is a need to determine whether or not COVID infection induces or unmasks new-onset/newly diagnosed hypertension/diabetes during the acute phase and post-COVID-19. Aim: In the current article, we discuss the current data at the intersection of COVID, hypertension, and COVID and diabetes, from prevalence, risk factors, and underlying mechanisms during an acute and post-COVID phase; focusing on new-onset hypertension and new onset type 2 diabetes. Method: We have performed a literature search via online databases such as PubMed/MEDLINE and Google Scholar from December 2019-August 2022. The data from various studies and review articles have been included. Results: Current evidence suggests the occurrence of new-onset hypertension and new onset type 2 diabetes in patients infected with the SARS-CoV-2 virus. Data also indicate a higher risk of negative outcomes in these patients. Conclusions: It is evident that the tenacity of these new-onset diseases post-COVID-19 is likely to have huge implications in terms of unexpected morbidity. Therefore, screening and follow-up of these patients seems reasonable. Clinicians shall have to deal with this evolving challenge and adequately equip themselves to address this facet of COVID-19 as well. Further data from various follow-up studies and registries like the CoviDIAB Project is required to be better equipped to propose exact recommendations for patients with NOD. On the contrary, more evidence is required for incidence and long-term sequelae for patients with new-onset hypertension. How to cite this article: Gupta A, Duggal R. Incidence of New-onset Hypertension and New-onset Type 2 Diabetes during or after SARS-CoV-2 Infection. J Assoc Physicians India 2023;71(10):78-82.

Exploration of high dimensional free energy landscapes by a combination of temperature-accelerated sliced sampling and parallel biasing.

Temperature-accelerated sliced sampling (TASS) is an enhanced sampling method for achieving accelerated and controlled exploration of high-dimensional free energy landscapes in molecular dynamics simulations. With the aid of umbrella bias potentials, the TASS method realizes a controlled exploration and divide-and-conquer strategy for computing high-dimensional free energy surfaces. In TASS, diffusion of the system in the collective variable (CV) space is enhanced with the help of metadynamics bias and elevated-temperature of the auxiliary degrees of freedom (DOF) that are coupled to the CVs. Usually, a low-dimensional metadynamics bias is applied in TASS. In order to further improve the performance of TASS, we propose here to use a highdimensional metadynamics bias, in the same form as in a parallel bias metadynamics scheme. Here, a modified reweighting scheme, in combination with artificial neural network is used for computing unbiased probability distribution of CVs and projections of high-dimensional free energy surfaces. We first validate the accuracy and efficiency of our method in computing the four-dimensional free energy landscape for alanine tripeptide in vacuo. Subsequently, we employ the approach to calculate the eight-dimensional free energy landscape of alanine pentapeptide in vacuo. Finally, the method is applied to a more realistic problem wherein we compute the broad four-dimensional free energy surface corresponding to the deacylation of a drug molecule which is covalently complexed with a ß-lactamase enzyme. We demonstrate that using parallel bias in TASS improves the efficiency of exploration of high-dimensional free energy landscapes.

Amyloids on Membrane Interfaces: Implications for Neurodegeneration.

Membrane interfaces are vital for various cellular processes, and their involvement in neurodegenerative disorders such as Alzheimer's and Parkinson's disease has taken precedence in recent years. The amyloidogenic proteins associated with neurodegenerative diseases interact with the neuronal membrane through various means, which has implications for both the onset and progression of the disease. The parameters that regulate the interaction between the membrane and the amyloids remain poorly understood. The review focuses on the various aspects of membrane interactions of amyloids, particularly amyloid-ß (Aß) peptides and Tau involved in Alzheimer's and α-synuclein involved in Parkinson's disease. The genetic, cell biological, biochemical, and biophysical studies that form the basis for our current understanding of the membrane interactions of Aß peptides, Tau, and α-synuclein are discussed.

Inking outside the box: systematic review on the utility of tattooing lesions in rectal cancer.

PURPOSE: Endoscopic tattooing in rectal cancer is infrequently utilized for fear of tattoo ink obscuring anatomical planes, increasing the difficulty of surgical excision. Colon cancer tattooing has demonstrated increased lymph node yields and increased accuracy in establishing adequate margins. Rectal cancer tattooing may be especially helpful after neoadjuvant chemoradiation, where complete clinical responses could limit lesion identification and lymph node yields are typically less robust. We seek to review and identify the effects of tattooing in rectal cancer. METHODS: A systematic literature search was performed in PubMed, Embase, and SCOPUS. Studies on endoscopic tattooing with cohorts consisting of at least ≥ 25% of rectal cancer patients were selected. Studies focusing solely on rectal cancer were also reviewed separately. RESULTS: Of 416 studies identified, 10 studies encompassing 2460 patients were evaluated. Seven studies evaluated lymph node yields; five reported beneficial effects of endoscopic tattooing, while two reported no significant difference. Among four studies reporting lesion localization, successful localization rates were between 63 and 100%. Rates of intraoperative endoscopy performed to reevaluate lesion location ranged from 5.7 to 20%. The distal margin was evaluated in two studies, which reported more accurate placement of the distal resection margin after tattooing. When complications of tattooing were documented (7 studies with 889 patients), only five direct complications of endoscopic tattooing were observed (0.6%). CONCLUSIONS: Although the data is heterogenous, it suggests that endoscopic tattooing in rectal cancer may improve lymph node yields and assist in determining accurate distal margins without high rates of complication. Further research must be completed before practice management guidelines can change. TRIAL REGISTRATION: No. CRD42021271784.

Computer-Vision-Based Vibration Tracking Using a Digital Camera: A Sparse-Optical-Flow-Based Target Tracking Method.

Computer-vision-based target tracking is a technology applied to a wide range of research areas, including structural vibration monitoring. However, current target tracking methods suffer from noise in digital image processing. In this paper, a new target tracking method based on the sparse optical flow technique is introduced for improving the accuracy in tracking the target, especially when the target has a large displacement. The proposed method utilizes the Oriented FAST and Rotated BRIEF (ORB) technique which is based on FAST (Features from Accelerated Segment Test), a feature detector, and BRIEF (Binary Robust Independent Elementary Features), a binary descriptor. ORB maintains a variety of keypoints and combines the multi-level strategy with an optical flow algorithm to search the keypoints with a large motion vector for tracking. Then, an outlier removal method based on Hamming distance and interquartile range (IQR) score is introduced to minimize the error. The proposed target tracking method is verified through a lab experiment-a three-story shear building structure subjected to various harmonic excitations. It is compared with existing sparse-optical-flow-based target tracking methods and target tracking methods based on three other types of techniques, i.e., feature matching, dense optical flow, and template matching. The results show that the performance of target tracking is greatly improved through the use of a multi-level strategy and the proposed outlier removal method. The proposed sparse-optical-flow-based target tracking method achieves the best accuracy compared to other existing target tracking methods.

Comparative evaluation of intracranial oligodendroglioma and astrocytoma of similar grades using conventional and T1-weighted DCE-MRI.

PURPOSE: This retrospective study was performed on a 3T MRI to determine the unique conventional MR imaging and T1-weighted DCE-MRI features of oligodendroglioma and astrocytoma and investigate the utility of machine learning algorithms in their differentiation. METHODS: Histologically confirmed, 81 treatment-naïve patients were classified into two groups as per WHO 2016 classification: oligodendroglioma (n = 16; grade II, n = 25; grade III) and astrocytoma (n = 10; grade II, n = 30; grade III). The differences in tumor morphology characteristics were evaluated using Z-test. T1-weighted DCE-MRI data were analyzed using an in-house built MATLAB program. The mean 90th percentile of relative cerebral blood flow, relative cerebral blood volume corrected, volume transfer rate from plasma to extracellular extravascular space, and extravascular extracellular space volume values were evaluated using independent Student's t test. Support vector machine (SVM) classifier was constructed to differentiate two groups across grade II, grade III, and grade II+III based on statistically significant features. RESULTS: Z-test signified only calcification among conventional MR features to categorize oligodendroglioma and astrocytoma across grade III and grade II+III tumors. No statistical significance was found in the perfusion parameters between two groups and its subtypes. SVM trained on calcification also provided moderate accuracy to differentiate oligodendroglioma from astrocytoma. CONCLUSION: We conclude that conventional MR features except calcification and the quantitative T1-weighted DCE-MRI parameters fail to discriminate between oligodendroglioma and astrocytoma. The SVM could not further aid in their differentiation. The study also suggests that the presence of more than 50% T2-FLAIR mismatch may be considered as a more conclusive sign for differentiation of IDH mutant astrocytoma.

A Retrospective Analysis of Fixed Combination of Empagliflozin and Linagliptin in Addition to the Existing Treatment for its Clinical Effectiveness in Adults with Type 2 Diabetes: A Real-World Clinical Experience.

BACKGROUND: The efficacy and safety of empagliflozin and linagliptin (Empa/Lina), is demonstrated in adults with T2DM in the various trials. The study was planned to investigate the clinical effectiveness and safety of Empa/Lina in a more representative population of the Indian outpatient setting. METHODS: The study was conducted in poorly controlled T2DM patients being treated with Empa/Lina once daily (25/5mg) as an add on in a tertiary care institute in Jammu, India. Various efficacy and safety parameters were assessed prior to the initiation of Empa/Lina and thereafter at periodic intervals until week 12. Appropriate statistical tests were applied. RESULTS: In a total of 347 eligible patients, the mean age (SD) was 57.84 ±7.3 years, Males were 49%, average body weight was 79.81±9.72 kg. The median duration of diabetes was 6.42±2.05 years. Empa/Lina as an add on therapy to other glucose-lowering treatment was associated with a significant lowering in HbA1c (-1.1 ±0.64 mg/dl), FPG level -47.11(±20.42) mg/dl, PPG level (-71.32± 26.56), body weight -2.64 (±1.97) kg and blood pressure parameters (systolic BP -7.68 ±5.2 and Diastolic BP -3.16±1.7) from baseline at 12 weeks. A total of 47.55 percent of patients responded to Empa/Lina (25/5mg) added in conjunction with other antidiabetes agents. There was no significant difference in glycemic parameters of various subgroups assessed based on concurrent antidiabetes drugs. However, a significant reduction in body weight of subjects on insulin therapy was noticed. There was an improvement in eGFR level which was maintained across the study period. Genital mycotic infection was reported in 8.6% of patients. Empa/Lina (25/5 mg) as an add-on therapy was well tolerated with less hypoglycemic events. DISCUSSION AND CONCLUSION: Thus, the combination of empagliflozin and linagliptin (25/5 mg) significantly improved the glycemic and non-glycemic measures in combination with one or more commonly prescribed antidiabetic drugs in inadequately controlled diabetes patients and is well tolerated.

Learning curves and the influence of procedural volume for the treatment of dysplastic Barrett's esophagus.

BACKGROUND AND AIMS: Endoscopic resections and radiofrequency ablation (RFA) are the established treatments for Barrett's-associated dysplasia and early esophageal neoplasia. The UK RFA Registry collects patient outcomes from 24 centers treating patients in the United Kingdom and Ireland. Learning curves for treatment of Barrett's dysplasia and the impact of center caseload on patient outcomes is still unknown. METHODS: We examined outcomes of 678 patients treated with RFA in the UK Registry using risk-adjusted cumulative sum control chart (RA-CUSUM) analysis to identify change points in complete resolution of intestinal metaplasia (CR-IM) and complete resolution of dysplasia (CR-D) outcomes. We compared outcomes between those treated at high-volume (>100 enrolled patients), medium-volume (51-100), and low-volume (<50) centers. RESULTS: There was no association between center volume and CR-IM and CR-D rates, but recurrence rates were lower in high-volume versus low-volume centers (log rank P = .001). There was a significant change point for outcomes at 12 cases for CR-D (reduction from 24.5% to 10.4%; P < .001) and at 18 cases for CR-IM (30.7% to 18.6%; P < .001) from RA-CUSUM curve analysis. CONCLUSION: Our data suggest that 18 supervised cases of endoscopic ablation may be required before competency in endoscopic treatment of Barrett's dysplasia can be achieved. The difference in outcomes between a high-volume and low-volume center does not support further centralization of services to only high-volume centers.

Uncertainty quantification in reconstruction of sparse water quality time series: Implications for watershed health and risk-based TMDL assessment.

Despite the plethora of methods available for uncertainty quantification, their use has been limited in the practice of water quality (WQ) modeling. In this paper, a decision support tool (DST) that yields a continuous time series of WQ loads from sparse data using streamflows as predictor variables is presented. The DST estimates uncertainty by analyzing residual errors using a relevance vector machine. To highlight the importance of uncertainty quantification, two applications enabled within the DST are discussed. The DST computes (i) probability distributions of four measures of WQ risk analysis- reliability, resilience, vulnerability, and watershed health- as opposed to single deterministic values and (ii) concentration/load reduction required in a WQ constituent to meet total maximum daily load (TMDL) targets along with the associated risk of failure. Accounting for uncertainty reveals that a deterministic analysis may mislead about the WQ risk and the level of compliance attained with established TMDLs.

Evaluation of Efficacy of Injectable-guided Tissue Regeneration with and without Clindamycin on the Colonization of Porphyromonas gingivalis by Real-time Polymerase Chain Reaction.

AIM: Aim of the present study was to evaluate the loading of clindamycin with injectable-guided tissue regeneration (GTR) will prevent the colonization of Porphyromonas gingivalis and to compare and assess the quantitative changes in P. gingivalis colony forming units (CFUs) by real-time polymerase chain reaction (PCR) analysis. MATERIALS AND METHODS: Thirty microbiological samples were pooled from the deepest periodontal pockets from the thirty sites from the two groups: group I-injectable GTR placed in the defect filled with demineralized freeze-dried bone allograft (DFDBA) and group II-clindamycin loaded injectable GTR placed in the defect filled with DFDBA. The total number of P. gingivalis CFUs was estimated using real-time PCR at baseline and 4 weeks after therapy. RESULTS: A significant reduction in P. gingivalis CFUs at the end of 4 weeks was seen in both groups. Comparative evaluations between both groups at 4 weeks were with a mean of 4.44 ± 2.28 and 4.75 ± 3.32, respectively. Though there was a significant reduction in group II, the difference was statistically insignificant. CONCLUSION: The results suggest that clindamycin is beneficial in reducing microbial infection and can potentiate regeneration through host modulation. CLINICAL SIGNIFICANCE: Injectable GTR has the ability to mold according to the defect size and shape and eliminates the need to manipulate the membrane as required for the conventional membrane.

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma.

BACKGROUND: The comparative efficacy of cisplatin (CDDP), carboplatin, and cetuximab (CTX) delivered concurrently with radiation for locally advanced oropharyngeal squamous cell carcinoma continues to be evaluated. METHODS: The linked Surveillance, Epidemiology, and End Results-Medicare database was used to identify and compare patient and disease profiles, mortality, toxicity, and overall cost for patients with oropharynx cancer undergoing definitive concurrent chemoradiation with CDDP, carboplatin, or CTX between 2006 and 2011. The human papillomavirus status was unknown. The primary outcome was 2-year overall survival (OS). RESULTS: Four hundred nine patients receiving concurrent CDDP (n = 167), carboplatin (n = 69), or CTX (n = 173) were included. Those who were older, those who were nonwhite, and those with a Charlson Comorbidity Index ≥ 2 were less likely to receive CDDP. Two-year OS was inferior with CTX (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.08-2.60; P = .020) and no different with carboplatin (HR, 1.31; 95% CI, 0.73-2.35; P = .362) in a Cox proportional hazards model (reference CDDP). There was no statistically significant difference between carboplatin and CTX (HR, 1.28; 95% CI, 0.77-2.14; P = .891). Rates of antiemetic use and hospital visits for nausea/emesis/diarrhea or dehydration were statistically higher with CDDP. Pneumonia rates were higher with carboplatin. In the multivariate model, the corrected mean per-patient spending was significantly higher for CTX and carboplatin than CDDP ($61,133 and $65,721 vs $48,709). CONCLUSIONS: Patients who received CDDP had improved OS. CDDP was also associated with slightly lower overall costs and higher antiemetic usage and hospital visit rates, although a strong selection bias was observed because those receiving CTX and carboplatin were older and had higher comorbidity scores.

Comparing outcome of radiofrequency ablation in Barrett's with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry.

BACKGROUND AND STUDY AIM: Mucosal neoplasia arising in Barrett's esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. PATIENTS AND METHODS: Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barrett's mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. RESULTS: A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %; P < 0.0001). The 12-month complete response for dysplasia and intestinal metaplasia were almost identical in the two cohorts (HGD 88 % and 76 %, respectively; IMC 87 % and 75 %, respectively; P = 0.7). Progression to invasive cancer was not significantly different at 12 months (HGD 1.8 %, IMC 3.8 %; P = 0.19). A trend towards slightly worse medium-term durability may be emerging in IMC patients (P = 0.08). In IMC, EMR followed by RFA was definitely associated with superior durability compared with RFA alone (P = 0.01). CONCLUSION: The Registry reports on endoscopic therapy for Barrett's neoplasia, representing real-life outcomes. Patients with IMC were more likely to have visible lesions requiring initial EMR than those with HGD, and may carry a higher risk of cancer progression in the medium term. The data consolidate the approach to ensuring that these patients undergo thorough endoscopic work-up, including EMR prior to RFA when necessary.

Concave or convex π-dimers: the role of the pancake bond in substituted phenalenyl radical dimers.

π-stacking in dimers of phenalenyl represents the prototypical pancake bonding between radicals. This type of π-stacking aggregate is a key structural motif in conducting organic and multifunctional materials. It is driven by the bonding combination of the singly occupied molecular orbitals (SOMOs) of the monomers resulting in π-stacking contacts that are significantly shorter than the sum of the van der Waals (vdW) radii. Analysis of 56 structures from the literature (mostly from the Cambridge Structural Database) coupled with DFT computations shows that the central CC contact in derivatives of phenalenyl does not contribute directly to the π-stacking pancake bonding in accordance with the fact that the SOMO coefficient is zero at the central carbon. This central CC contact is typically longer than the contacts between the SOMO bearing α-carbons with a convex dimer shape with one known exception of a complex containing bulky tert-butyl groups. This unusual case of a concave shaped dimer with a significantly shorter central CC contact is due to the steric repulsions at the periphery of the molecule pushing the central atoms closer together relative to the α-α-contacts which provide the attractive driving force for the multicenter pancake bonding. The diradical character of the pancake bonding is revealed by the analysis of the unpaired electron density based on high-level multireference theory.