Laparoscopic Conversion to Open Cholecystectomy: Is Incidental Gallbladder Cancer Any Different?

BACKGROUND: A majority of gallbladder cancers present incidentally. Operative risk factors and outcomes for laparoscopic converted to open cholecystectomy in incidental gallbladder cancer are not well characterized. METHODS: Patients with incidental gallbladder cancer and acute cholecystitis undergoing laparoscopic cholecystectomy and conversion to open cholecystectomy in the National Surgical Quality Improvement Program (NSQIP) database of the American College of Surgeons (ACS) from 2010-2019 were reviewed. The primary endpoint was risk factors for conversion to open cholecystectomy in incidental gallbladder cancer. Chi-squared test or Fisher's exact test was used for categorical variables. Continuous variables were compared using the Mann-Whitney U test. RESULTS: A total of 5,789 patients undergoing laparoscopic cholecystectomy were identified, of which, 50 (0.9%) had incidental gallbladder cancer. For incidental gallbladder cancer patients, there were no differences in preoperative profile and risk factors between laparoscopic and converted to open cholecystectomy groups. Incidental carcinoma patients undergoing conversion to open cholecystectomy had lower preoperative sodium levels than the laparoscopic cholecystectomy group (P=0.007). Hospital length of stay (days) was longer for those with a conversion to open cholecystectomy for incidental carcinoma compared to non-conversion, 14 (10.8, 18.8) vs 2 (0.3, 5) (P=0.004). The patients converted to open cholecystectomy also had higher rates of postoperative sepsis (50% vs 0%, P<0.001) and reoperation than the laparoscopic cohort (50% vs 2.2%, P<0.001). Readmission and mortality rates, among other complications, were not significantly different between both surgical approaches in incidental gallbladder cancer patients. CONCLUSIONS:  Patients with conversion to open cholecystectomy had worse outcomes including longer hospital stays and higher rates of sepsis and reoperation. It remains difficult to predict which incidental gallbladder patients will require a conversion to open surgery. Further study examining whether more complicated recovery results in worse oncologic outcomes is warranted.

Temporal patterns in multiple stressors shape the vulnerability of overwintering Arctic zooplankton.

The Arctic polar nights bring extreme environmental conditions characterised by cold and darkness, which challenge the survival of organisms in the Arctic. Additionally, multiple anthropogenic stressors can amplify the pressure on the fragile Arctic ecosystems during this period. Determining how multiple anthropogenic stressors may affect the survival of Arctic life is crucial for ecological risk assessments and management, but this topic is understudied. For the first time, our study investigates the complex interactions of multiple stressors, exploring stressor temporal dynamics and exposure duration on a key Arctic copepod Calanus glacialis during the polar nights. We conducted experiments with pulse (intermittent) and press (continuous) exposure scenarios, involving microplastics, pyrene and warming in a fully factorial design. We observed significant effects on copepod survival, with pronounced impacts during later stressor phases. We also detected two-way interactions between microplastics and pyrene, as well as pyrene and warming, further intensified with the presence of a third stressor. Continuous stressor exposure for 9 days (press-temporal scenario) led to greater reductions in copepod survival compared to the pulse-temporal scenario, characterised by two 3-day stressor exposure phases. Notably, the inclusion of recovery phases, free from stressor exposure, positively influenced copepod survival, highlighting the importance of temporal exposure dynamics. We did not find behaviour to be affected by the different treatments. Our findings underscore the intricate interactions amongst multiple stressors and their temporal patterns in shaping the vulnerability of overwintering Arctic copepods with crucial implications for managing Arctic aquatic ecosystems under the fastest rate of ongoing climate change on earth.

Studying interactions among anthropogenic stressors in freshwater ecosystems: A systematic review of 2396 multiple-stressor experiments.

Understanding the interactions among anthropogenic stressors is critical for effective conservation and management of ecosystems. Freshwater scientists have invested considerable resources in conducting factorial experiments to disentangle stressor interactions by testing their individual and combined effects. However, the diversity of stressors and systems studied has hindered previous syntheses of this body of research. To overcome this challenge, we used a novel machine learning framework to identify relevant studies from over 235,000 publications. Our synthesis resulted in a new dataset of 2396 multiple-stressor experiments in freshwater systems. By summarizing the methods used in these studies, quantifying trends in the popularity of the investigated stressors, and performing co-occurrence analysis, we produce the most comprehensive overview of this diverse field of research to date. We provide both a taxonomy grouping the 909 investigated stressors into 31 classes and an open-source and interactive version of the dataset (https://jamesaorr.shinyapps.io/freshwater-multiple-stressors/). Inspired by our results, we provide a framework to help clarify whether statistical interactions detected by factorial experiments align with stressor interactions of interest, and we outline general guidelines for the design of multiple-stressor experiments relevant to any system. We conclude by highlighting the research directions required to better understand freshwater ecosystems facing multiple stressors.

Impact of Soil Fertilization with Pig Slurry on Antibiotic Residues and Resistance Genes: A Longitudinal Study.

The impact of soil fertilization with animal manure on the spread and persistence of antibiotic resistance in the environment is far from being fully understood. To add knowledge about persistence and correlations between antibiotic residues and antibiotic resistance genes (ARGs) in fertilized soil, a longitudinal soil mesocosm study was conducted. Soil samples were collected from the mesocosms immediately before spreading and then afterward at fifteen time points during a 320-day observation period. Eight ARGs (ermB, sul1, tetA, tetG, tetM, cfr, fexA, and optrA) and the class 1 integron-integrase gene, intI1, were determined in both pig slurry and soil, as well as residues of 36 antibiotics. Soil chemical and biochemical parameters were also measured. Twelve antibiotics were detected in the slurry in the range of 3 µg kg-1-3605 µg kg-1, with doxycycline, lincomycin, and tiamulin being the most abundant, whereas ermB, sul1, and tetM were the predominant ARGs. Before spreading, neither antibiotic residues nor ARGs were detectable in the soil; afterwards, their concentrations mirrored those in the slurry, with a gradual decline over the duration of the experiment. After about three months, the effect of the amendment was almost over, and no further evolution was observed.

Physical activity and exercise health benefits: cancer prevention, interception, and survival.

Physical activity (PA) has an established role in the promotion of health and fitness and the prevention of disease. Expected overall benefits include reduction of all-cause morbidity and death, weight control, improved quality of life, improved bone health and decreased falls of elderly subjects, , deeper cognition, and reduced risk of depression, anxiety, and sleeplessness. Currently, PA is a mainstay in the management of cardiovascular diseases, metabolic syndrome, diabetes, and bone health. Recently, the perception of its role in primary and secondary prevention, interception, and treatment of cancer, however, is also gaining importance. Regular walking, the simplest type of PA, is associated with reduced all-cause and cardiovascular disease mortality, and a role in cancer prevention is of increasing interest. Furthermore, PA improves the quality of life of cancer patients, attenuating side effects of chemotherapy, decreasing sarcopenia, increasing fitness, and inhibiting the recurrence and progression of some cancer types. It promotes emotional and psychological benefits in patients, inducing positive changes. While mechanisms, effective levels and useful amount of PA practice are well established in cardiology, they are yet to be fully determined in oncology. Nevertheless, PA is recommended to reduce cancer risk in the general population, and it has been introduced in programs for the prevention of second cancers. In perspective, it will help as integrative therapy in cancer patients and for cancer survivors. The number of beneficial effects in the cancer continuum is highlighted in this review.

Update on "Cell Therapy" Clinics Offering Treatments of Ocular Conditions Using Direct-To-Consumer Marketing Websites in the U.S.

PURPOSE: To assess the scope of U.S.-based companies advertising and administering non-Federal Drug Administration (FDA) approved cell-based therapy (herein called NFACT) for ocular conditions based on information from companies' public websites after the FDA's legal actions against specific NFACT clinics in 2018 and 2019. Current findings are compared to previously published data from 2017. DESIGN: Trend study looking at U.S.-based companies that use direct-to-consumer marketing and have websites advertising therapy for ocular conditions. METHODS: A systematic and extensive keyword-based Internet search was utilized to identify, document, and analyze U.S. business websites offering NFACT for ocular conditions as of August 2022. Main outcomes measured include, clinic locations, marketed ocular conditions, types of NFACT offered, source of stem cells used, routes of administration, and treatment costs. RESULTS: From the prior analysis in 2017 to the 2019 analysis, there was a decrease in the number of NFACT clinics from 76 to 62 and companies from 40 to 39. Given the concerning persistence of NFACTs in August 2019 an additional analysis was performed in 2022 which showed a drastic decrease in NFACT clinics from 62 in 2019 to 18 in 2023 and from 39 companies to 13 in 2023. In both 2019 and 2022, the most commonly referenced ocular condition was age-related macular degeneration (2019 - 72%, 2022 - 92%). The state with the most clinics was in Texas (2019 - 12; 2022 - 5). Autologous adipose-derived stem cells were the most common cell type used in both analyses. CONCLUSIONS: In 2019 U.S.-based direct-to-consumer companies marketing NFACT persisted despite (1) a lack of high-quality clinical evidence supporting the efficacy of these procedures, (2) the association of some of these treatments with severe vision loss, and (3) increasing FDA oversight and recent legal action. In 2022 the number of clinics and companies decreased, but their persistence is a reminder that continued concern is necessary and ophthalmic associations need to continue advocacy efforts to protect patients from these potentially predatory organizations.

Micro-Inclusion Engineering via Sc Incompatibility for Luminescence and Photoconversion Control in Ce3+-Doped Tb3Al5-xScxO12 Garnet.

Aluminum garnets display exceptional adaptability in incorporating mismatching elements, thereby facilitating the synthesis of novel materials with tailored properties. This study explored Ce3+-doped Tb3Al5-xScxO12 crystals (where x ranges from 0.5 to 3.0), revealing a novel approach to control luminescence and photoconversion through atomic size mismatch engineering. Raman spectroscopy confirmed the coexistence of garnet and perovskite phases, with Sc substitution significantly influencing the garnet lattice and induced A1g mode softening up to Sc concentration x = 2.0. The Sc atoms controlled sub-eutectic inclusion formation, creating efficient light scattering centers and unveiling a compositional threshold for octahedral site saturation. This modulation enabled the control of energy transfer dynamics between Ce3+ and Tb3+ ions, enhancing luminescence and mitigating quenching. The Sc admixing process regulated luminous efficacy (LE), color rendering index (CRI), and correlated color temperature (CCT), with adjustments in CRI from 68 to 84 and CCT from 3545 K to 12,958 K. The Ce3+-doped Tb3Al5-xScxO12 crystal (where x = 2.0) achieved the highest LE of 114.6 lm/W and emitted light at a CCT of 4942 K, similar to daylight white. This approach enables the design and development of functional materials with tailored optical properties applicable to lighting technology, persistent phosphors, scintillators, and storage phosphors.

Invasive lobular breast cancer: Focus on prevention, genetics, diagnosis, and treatment.

Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives.

The Past and Future of Angiogenesis as a Target for Cancer Therapy and Prevention.

Cancer growth is dependent on angiogenesis, the formation of new blood vessels, which represents a hallmark of cancer. After this concept was established in the 1970s, inhibition of tumor development and metastases by blocking the neoangiogenic process has been an important approach to the treatment of tumors. However, antiangiogenic therapies are often administered when cancer has already progressed. The key to reducing the cancer burden is prevention. We noticed 20 years ago that a series of possible cancer chemopreventive agents showed antiangiogenic properties when tested in experimental models. This article reviews the relevant advances in the understanding of the rationale for targeting angiogenesis for cancer therapy, prevention, and interception and recently investigated substances with antiangiogenic activity that may be suitable for such strategies. Many compounds, either dietary derivatives or repurposed drugs, with antiangiogenic activity are possible tools for cancer angioprevention. Such molecules have a favorable safety profile and are likely to allow the prolonged duration necessary for an efficient preventive strategy. Recent evidence on mechanisms and possible use is described here for food derivatives, including flavonoids, retinoids, triterpenoids, omega fatty acids, and carotenoids from marine microorganisms. As examples, a number of compounds, including epigallocatechin, resveratrol, xanthohumol, hydroxytyrosol, curcumin, fenretinide, lycopene, fucoxanthin, and repurposed drugs, such as aspirin, ß blockers, renin-angiotensin-aldosterone inhibitors, carnitines, and biguanides, are reviewed.

Biocompatible cellulose nanocrystal-based Trojan horse enables targeted delivery of nano-Au radiosensitizers to triple negative breast cancer cells.

A hybrid cellulose-based programmable nanoplatform for applications in precision radiation oncology is described. Here, sugar heads work as tumor targeting moieties and steer the precise delivery of radiosensitizers, i.e. gold nanoparticles (AuNPs) into triple negative breast cancer (TNBC) cells. This "Trojan horse" approach promotes a specific and massive accumulation of radiosensitizers in TNBC cells, thus avoiding the fast turnover of small-sized AuNPs and the need for high doses of AuNPs for treatment. Application of X-rays resulted in a significant increase of the therapeutic effect while delivering the same dose, showing the possibility to use roughly half dose of X-rays to obtain the same radiotoxicity effect. These data suggest that this hybrid nanoplatform acts as a promising tool for applications in enhancing cancer radiotherapy effects with lower doses of X-rays.

SETDB1 modulates the TGFß response in Duchenne muscular dystrophy myotubes.

Overactivation of the transforming growth factor-ß (TGFß) signaling in Duchenne muscular dystrophy (DMD) is a major hallmark of disease progression, leading to fibrosis and muscle dysfunction. Here, we investigated the role of SETDB1 (SET domain, bifurcated 1), a histone lysine methyltransferase involved in muscle differentiation. Our data show that, following TGFß induction, SETDB1 accumulates in the nuclei of healthy myotubes while being already present in the nuclei of DMD myotubes where TGFß signaling is constitutively activated. Transcriptomics revealed that depletion of SETDB1 in DMD myotubes leads to down-regulation of TGFß target genes coding for secreted factors involved in extracellular matrix remodeling and inflammation. Consequently, SETDB1 silencing in DMD myotubes abrogates the deleterious effect of their secretome on myoblast differentiation by impairing myoblast pro-fibrotic response. Our findings indicate that SETDB1 potentiates the TGFß-driven fibrotic response in DMD muscles, providing an additional axis for therapeutic intervention.

Pulmonary Artery Stenosis After an Orthotopic Heart Transplantation: A Case Report With Cardiac Imaging Findings and a Literature Review.

Pulmonary artery stenosis is a rare complication of heart transplantation. It is typically a congenital condition or can be secondary to rheumatic fever, systemic vasculitis like Behcet's disease, or Takayasu's arteritis. It can also occur as a rarity of a delayed complication post-heart transplant. In this report, we describe the imaging findings of pulmonary artery stenosis in a patient who underwent an orthotopic heart transplant more than 10 years prior. Dynamic cardiac magnetic resonance imaging (MRI), phase contrast imaging, and MR angiography in the management of pulmonary artery stenosis helped in heart and pulmonary circulation. Functional evaluation can be achieved with current multichannel transmit-receive coils. Cardiac gated pre- and dynamic contrast-enhanced MR was performed with phase-contrast imaging for further evaluation confirming the diagnosis of pulmonary artery stenosis.

Na3MnTi(PO4)3/C Nanofiber Free-Standing Electrode for Long-Cycling-Life Sodium-Ion Batteries.

Self-standing Na3MnTi(PO4)3/carbon nanofiber (CNF) electrodes are successfully synthesized by electrospinning. A pre-synthesized Na3MnTi(PO4)3 is dispersed in a polymeric solution, and the electrospun product is heat-treated at 750 °C in nitrogen flow to obtain active material/CNF electrodes. The active material loading is 10 wt%. SEM, TEM, and EDS analyses demonstrate that the Na3MnTi(PO4)3 particles are homogeneously spread into and within CNFs. The loaded Na3MnTi(PO4)3 displays the NASICON structure; compared to the pre-synthesized material, the higher sintering temperature (750 °C) used to obtain conductive CNFs leads to cell shrinkage along the a axis. The electrochemical performances are appealing compared to a tape-casted electrode appositely prepared. The self-standing electrode displays an initial discharge capacity of 124.38 mAh/g at 0.05C, completely recovered after cycling at an increasing C-rate and a coulombic efficiency ≥98%. The capacity value at 20C is 77.60 mAh/g, and the self-standing electrode exhibits good cycling performance and a capacity retention of 59.6% after 1000 cycles at 1C. Specific capacities of 33.6, 22.6, and 17.3 mAh/g are obtained by further cycling at 5C, 10C, and 20C, and the initial capacity is completely recovered after 1350 cycles. The promising capacity values and cycling performance are due to the easy electrolyte diffusion and contact with the active material, offered by the porous nature of non-woven nanofibers.

Design of Na3MnZr(PO4)3/Carbon Nanofiber Free-Standing Cathodes for Sodium-Ion Batteries with Enhanced Electrochemical Performances through Different Electrospinning Approaches.

The NASICON-structured Na3MnZr(PO4)3 compound is a promising high-voltage cathode material for sodium-ion batteries (SIBs). In this study, an easy and scalable electrospinning approach was used to synthesize self-standing cathodes based on Na3MnZr(PO4)3 loaded into carbon nanofibers (CNFs). Different strategies were applied to load the active material. All the employed characterization techniques (X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), thermal gravimetric analysis (TGA), and Raman spectroscopy) confirmed the successful loading. Compared to an appositely prepared tape-cast electrode, Na3MnZr(PO4)3/CNF self-standing cathodes demonstrated an enhanced specific capacity, especially at high C-rates, thanks to the porous conducive carbon nanofiber matrix. Among the strategies applied to load Na3MnZr(PO4)3 into the CNFs, the electrospinning (vertical setting) of the polymeric solution containing pre-synthesized Na3MnZr(PO4)3 powders resulted effective in obtaining the quantitative loading of the active material and a homogeneous distribution through the sheet thickness. Notably, Na3MnZr(PO4)3 aggregates connected to the CNFs, covered their surface, and were also embedded, as demonstrated by TEM and EDS. Compared to the self-standing cathodes prepared with the horizontal setting or dip-drop coating methods, the vertical binder-free electrode exhibited the highest capacity values of 78.2, 55.7, 38.8, 22.2, 16.2, 12.8, 10.3, 9.0, and 8.5 mAh/g at C-rates of 0.05C, 0.1C, 0.2C, 0.5C, 1C, 2C, 5C, 10C, and 20C, respectively, with complete capacity retention at the end of the measurements. It also exhibited a good cycling life, compared to its tape-cast counterpart: it displayed higher capacity retention at 0.2C and 1C, and, after cycling 1000 cycles at 1C, it could be further cycled at 5C, 10C, and 20C.

Navigating resistance to ALK inhibitors in the lorlatinib era: a comprehensive perspective on NSCLC.

INTRODUCTION: The emergence of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC) has revolutionized targeted therapy. This dynamic landscape, featuring novel ALK inhibitors and combination therapies, necessitates a profound understanding of resistance mechanisms for effective treatment strategies. Recognizing two primary categories - on-target and off-target resistance - underscores the need for comprehensive assessment. AREAS COVERED: This review delves into the intricacies of resistance to ALK inhibitors, exploring complexities in identification and management. Molecular testing, pivotal for early detection and accurate diagnosis, forms the foundation for patient stratification and resistance management. The literature search methodology involved comprehensive exploration of Pubmed and Embase. The multifaceted perspective encompasses new therapeutic horizons, ongoing clinical trials, and their clinical implications post the recent approval of lorlatinib. EXPERT OPINION: Our expert opinion encapsulates the critical importance of understanding resistance mechanisms in the context of ALK inhibitors for shaping successful treatment approaches. With a focus on molecular testing and comprehensive assessment, this review contributes valuable insights to the evolving landscape of NSCLC therapy.

Intra- and post-pandemic impact of the COVID-19 outbreak on Stanford Health Care.

Stanford Health Care, which provides about 7% of overall healthcare to approximately 9 million people in the San Francisco Bay Area, has undergone significant changes due to the opening of a second hospital in late 2019 and, more importantly, the COVID-19 pandemic. We examine the impact of these events on anatomic pathology (AP) cases, aiming to enhance operational efficiency in response to evolving healthcare demands. We extracted historical census, admission, lab tests, operation, and AP data since 2015. An approximately 45% increase in the volume of laboratory tests (P < 0.0001) and a 17% increase in AP cases (P < 0.0001) occurred post-pandemic. These increases were associated with progressively increasing (P < 0.0001) hospital census. Census increase stemmed from higher admission through the emergency department (ED), and longer lengths of stay mostly for transfer patients, likely due to the greater capability of the new ED and changes in regional and local practice patterns post-pandemic. Higher census led to overcapacity, which has an inverted U relationship that peaked at 103% capacity for AP cases and 114% capacity for laboratory tests. Overcapacity led to a lower capability to perform clinical activities, particularly those related to surgical procedures. We conclude by suggesting parameters for optimal operations in the post-pandemic era.

Tularemia on the rise in Switzerland? A one health approach is needed!

In the last 10 years, an increase in tularemia cases has been observed in both humans and animals in Switzerland. In these, infection with Francisella tularensis, the causative agent of the zoonotic disease tularemia, can occur through arthropod vectors or contact to infected animals or exposure to contaminated environmental sources. Currently, we are only able to postulate potential aetiologies: (i) behavioral changes of humans with more exposure to endemic habitats of infected arthropod vectors; (ii) an increased rate of tularemia infected ticks; (iii) increasing number and geographical regions of tick biotopes; (iv) increasing and/or more diverse reservoir populations; (v) increasing presence of bacteria in the environment; (vi) raised awareness and increased testing among physicians; (vii) improved laboratory techniques including molecular testing. To approach these questions, a one-health strategy is necessary. A functioning collaboration between public health, human medicine, and diagnostic and veterinary units for the control of tularemia must be established. Furthermore, the public should be included within citizen-supported-science-projects.

Spectrogram Inversion for Reconstruction of Electric Currents at Industrial Frequencies: A Deep Learning Approach.

In this paper, we present a deep learning approach for identifying current intensity and frequency. The reconstruction is based on measurements of the magnetic field generated by the current flowing in a conductor. Magnetic field data are collected using a magnetic probe capable of generating a spectrogram, representing the spectrum of frequencies of the magnetic field over time. These spectrograms are saved as images characterized by color density proportional to the induction field value at a given frequency. The proposed deep learning approach utilizes a convolutional neural network (CNN) with the spectrogram image as input and the current or frequency value as output. One advantage of this approach is that current estimation is achieved contactless, using a simple magnetic field probe positioned close to the conductor.