Percutaneous Microwave Ablation versus Cryoablation for Small Renal Masses (≤4 cm): 12-Year Experience at a Single Center.

PURPOSE: To determine whether microwave ablation (MWA) has equivalent outcomes to those of cryoablation (CA) in terms of technical success, adverse events, local tumor recurrence, and survival in adult patients with solid enhancing renal masses ≤4 cm. MATERIALS AND METHODS: A retrospective review was performed of 279 small renal masses (≤4 cm) in 257 patients (median age, 71 years; range, 40-92 years) treated with either CA (n = 191) or MWA (n = 88) between January 2008 and December 2020 at a single high-volume institution. Evaluations of adverse events, treatment effectiveness, and therapeutic outcomes were conducted for both MWA and CA. Disease-free, metastatic-free, and cancer-specific survival rates were tabulated. The estimated glomerular filtration rate was employed to examine treatment-related alterations in renal function. RESULTS: No difference in patient age (P = .99) or sex (P = .06) was observed between the MWA and CA groups. Cryoablated lesions were larger (P < .01) and of greater complexity (P = .03). The technical success rate for MWA was 100%, whereas 1 of 191 cryoablated lesions required retreatment for residual tumor. There was no impact on renal function after CA (P = .76) or MWA (P = .49). Secondary analysis using propensity score matching demonstrated no significant differences in local recurrence rates (P = .39), adverse event rates (P = .20), cancer-free survival (P = .76), or overall survival (P = .19) when comparing matched cohorts of patients who underwent MWA and CA. CONCLUSIONS: High technical success and local disease control were achieved for both MWA and CA. Cancer-specific survival was equivalent. Higher adverse event rates after CA may reflect the tendency to treat larger, more complex lesions with CA.

Contemporary report of surgical outcomes after single-stage total pancreatectomy: A 10-year experience.

BACKGROUND: Surgeons rarely perform elective total pancreatectomy (TP). Our study seeks to report surgical outcomes in a contemporary series of single-stage (SS) TP patients. METHODS: Between the years 2013 to 2023 we conducted a retrospective review of 60 consecutive patients who underwent SSTP. Demographics, pathology, treatment-related variables, and survival were recorded and analyzed. RESULTS: SSTP consisted of 3% (60/1859) of elective pancreas resections conducted. Patient median age was 68 years. Ninety percent of these patients (n = 54) underwent SSTP for pancreatic ductal adenocarcinoma (PDAC). Conversion from a planned partial pancreatectomy to TP occurred intraoperatively in 31 (52%) patients. Fifty-nine patients (98%) underwent an R0 resection. Median length of hospital stay was 6 days. The majority of morbidities were minor, with 27% patients (n = 16) developing severe complications (Clavien-Dindo ≥3). Thirty and ninety-day mortality rates were 1.67% (one patient) and 5% (three patients), respectively. Median survival for the entire cohort was 24.4 months; 22.7 months for PDAC patients, with 1-, 3-, and 5-year survival of 68%, 43%, and 16%, respectively. No mortality occurred in non-PDAC patients (n = 6). CONCLUSION: Elective single-stage total pancreatectomy can be a safe and appropriate treatment option. SSTP should be in the armamentarium of surgeons performing pancreatic resection.

Implementation of an opioid reduction toolkit in pancreatectomy patients significantly increases patient awareness of safe practice and decreases amount prescribed and consumed.

BACKGROUND: Postoperative opioid abuse following surgery is a major concern. This study sought to create an opioid reduction toolkit to reduce the number of narcotics prescribed and consumed while increasing awareness of safe disposal in pancreatectomy patients. METHODS: Prescription, consumption, and refill request data for postoperative opioids were collected from patients receiving an open pancreatectomy before and after the implementation of an opioid reduction toolkit. Outcomes included safe disposal practice awareness for unused medication. RESULTS: 159 patients were included in the study: 24 in the pre-intervention and 135 in the post-intervention group. No significant demographic or clinical differences existed between groups. Median morphine milliequivalents (MMEs) prescribed were significantly reduced from 225 (225-310) to 75 (75-113) in the post-intervention group (p < 0.0001). Median MMEs consumed were significantly reduced from 109 (111-207) to 15 (0-75), p < 0.0001), as well. Refill request rates remained equivalent during the study (Pre: 17% v Post: 13%, p = 0.9) while patient awareness of safe disposal increased (Pre: 25% v Post: 62%, p < 0.0001). DISCUSSION: An opioid reduction toolkit significantly reduced the number of postoperative opioids prescribed and consumed after open pancreatectomy, while refill request rates remained the same and patients' awareness of safe disposal increased.

Living materials with programmable functionalities grown from engineered microbial co-cultures.

Biological systems assemble living materials that are autonomously patterned, can self-repair and can sense and respond to their environment. The field of engineered living materials aims to create novel materials with properties similar to those of natural biomaterials using genetically engineered organisms. Here, we describe an approach to fabricating functional bacterial cellulose-based living materials using a stable co-culture of Saccharomyces cerevisiae yeast and bacterial cellulose-producing Komagataeibacter rhaeticus bacteria. Yeast strains can be engineered to secrete enzymes into bacterial cellulose, generating autonomously grown catalytic materials and enabling DNA-encoded modification of bacterial cellulose bulk properties. Alternatively, engineered yeast can be incorporated within the growing cellulose matrix, creating living materials that can sense and respond to chemical and optical stimuli. This symbiotic culture of bacteria and yeast is a flexible platform for the production of bacterial cellulose-based engineered living materials with potential applications in biosensing and biocatalysis.

The human claustrum tracks slow waves during sleep.

Slow waves are a distinguishing feature of non-rapid-eye-movement (NREM) sleep, an evolutionarily conserved process critical for brain function. Non-human studies posit that the claustrum, a small subcortical nucleus, coordinates slow waves. We recorded claustrum neurons in humans during sleep. In contrast to neurons from other brain regions, claustrum neurons increased their activity and tracked slow waves during NREM sleep suggesting that the claustrum plays a role in human sleep architecture.

Problems With Magnetic Resonance Imaging-Conditional Anesthesia Machine During Routine Imaging: A Near-Miss Case Report.

Delivering safe anesthesia care in the magnetic resonance imaging (MRI) scanner presents many unique challenges. We present a case report of how an MRI-conditional anesthesia machine malfunctioned after being pulled toward an MRI scanner during routine imaging, not previously reported in the literature. This near-miss event emphasizes the continued need for staff education and vigilance.

AI in healthcare: navigating opportunities and challenges in digital communication.

The landscape of healthcare communication is undergoing a profound transformation in the digital age, and at the heart of this evolution are AI-powered chatbots. This mini-review delves into the role of AI chatbots in digital health, providing a detailed exploration of their applications, benefits, challenges, and future prospects. Our focus is on their versatile applications within healthcare, encompassing health information dissemination, appointment scheduling, medication management, remote patient monitoring, and emotional support services. The review underscores the compelling advantages of AI chatbots. However, it also addresses the significant challenges posed by the integration of AI tools into healthcare communication.

Refractory Hyperactive Delirium Without Intravenous Access: A Case Report.

Refractory delirium is a complex, often underdiagnosed, and difficult-to-treat phenomenon. It poses significant challenges to healthcare providers, especially in patients without prior intravenous access. In extreme cases, anesthetic management may be needed to treat refractory delirium. Here, we present a unique case of postoperative hyperactive refractory delirium in a patient without intravenous access, ultimately requiring anesthetic management for resolution.

Antibiotic stewardship with upper respiratory tract infection patients at student health centers: Providers' communication experiences and strategies.

BACKGROUND: Effective provider-patient communication can improve antibiotic stewardship in primary care, but providers find it challenging to discuss antibiotics with patients. This study, focused on college student health centers, examines patients' tactics for obtaining antibiotics for upper respiratory tract infections and providers' communication strategies for improving patient understanding and reducing demand. METHODS: Health care providers (N = 103) employed at student health centers on large and primarily residential college campuses in the U.S. completed an online survey. RESULTS: Providers perceived patients as wanting antibiotics in approximately 50% of upper respiratory tract infection visits and noted multiple patient tactics to obtain them, including reports of prior prescribing, suggested diagnoses, and direct requests. Providers used multiple strategies to manage patient demand, including explanation of the diagnosis, antibiotic utility and risks, and treatment plan. DISCUSSION: This study extends prior research indicating that patients exercise a range of influence tactics to obtain antibiotics, and thereby create discomfort for providers. The study also elucidates providers' efforts to counter these influence tactics and steward antibiotics by educating patients. CONCLUSIONS: Additional research is needed to specify the most effective ways for providers to respond to patients' influence tactics, including the best approaches to explaining diagnosis, treatment, and antibiotic resistance.

Isolated cerebral Mucormycosis and Aspergillosis coinfection in an immunocompromised adult.

Opportunistic fungal infections are a major cause of mortality in immunosuppressed patients, with mucormycosis and aspergillosis as two of the most commonly identified fungal organisms. Coinfection with mucormycosis and aspergillosis is rare, but cases have been reported in literature, most commonly presenting as disseminated invasive fungal infection with cerebrorhino-orbital involvement in an immunocompromised patient. Infections are most commonly caused by direct implantation of spores with localised angioinvasion. Haematogenous spread is rare, with most cases secondary to haematological malignancies or intravenous drug use. Coinfection with mucormycosis and aspergillosis portends a poor prognosis, with a high mortality rate. Thus, prompt recognition and intervention are crucial to prevent poor outcomes. In this unique case report, we describe a case of isolated cerebral mucormycosis and aspergillosis coinfection, not previously reported in literature.

Improve the Colorectal Cancer Diagnosis Using Gut Microbiome Data.

In the United States, colorectal cancer is the second largest cause of cancer death, and accurate early detection and identification of high-risk patients is a high priority. Although fecal screening tests are available, the close relationship between colorectal cancer and the gut microbiome has generated considerable interest. We describe a machine learning method for gut microbiome data to assist in diagnosing colorectal cancer. Our methodology integrates feature engineering, mediation analysis, statistical modeling, and network analysis into a novel unified pipeline. Simulation results illustrate the value of the method in comparison to existing methods. For predicting colorectal cancer in two real datasets, this pipeline showed an 8.7% higher prediction accuracy and 13% higher area under the receiver operator characteristic curve than other published work. Additionally, the approach highlights important colorectal cancer-related taxa for prioritization, such as high levels of Bacteroides fragilis, which can help elucidate disease pathology. Our algorithms and approach can be widely applied for Colorectal cancer prediction using either 16 S rRNA or shotgun metagenomics data.

Lidocaine infusions for refractory chronic migraine: a retrospective analysis.

INTRODUCTION: Patients with refractory chronic migraine have poor quality of life. Intravenous infusions are indicated to rapidly 'break the cycle' of pain. Lidocaine infusions may be effective but evidence is limited. METHODS: The records of 832 hospital admissions involving continuous multiday lidocaine infusions for migraine were reviewed. All patients met criteria for refractory chronic migraine. During hospitalization, patients received additional migraine medications including ketorolac, magnesium, dihydroergotamine, methylprednisolone, and neuroleptics. The primary outcome was change in headache pain from baseline to hospital discharge. Secondary outcomes measured at the post-discharge office visit (25-65 days after treatment) included headache pain and the number of headache days, and percentage of sustained responders. Percentage of acute responders, plasma lidocaine levels, and adverse drug effects were also determined. RESULTS: In total, 609 patient admissions met criteria. The mean age was 46±14 years; 81.1% were female. Median pain rating decreased from baseline of 7.0 (5.0-8.0) to 1.0 (0.0-3.0) at end of hospitalization (p<0.001); 87.8% of patients were acute responders. Average pain (N=261) remained below baseline at office visit 1 (5.5 (4.0-7.0); p<0.001). Forty-three percent of patients were sustained responders at 1 month. Headache days (N=266) decreased from 26.8±3.9 at baseline to 22.5±8.3 at the post-discharge office visit (p<0.001). Nausea and vomiting were the most common adverse drug effects and all were mild. CONCLUSION: Lidocaine infusions may be associated with short-term and medium-term pain relief in refractory chronic migraine. Prospective studies should confirm these results.

Detection of Human Papillomavirus Integration in Brain Metastases from Oropharyngeal Tumors by Targeted Sequencing.

Human papillomavirus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC) are known to have differential phenotypes, including the incidence and location of metastases. HPV positive (HPV+) HNSCC are more likely to metastasize to distant sites, such as the lung, brain, and skin. Among these locations, metastasis to the brain is a rare event, and little is known about specific risk factors for this phenotype. In this report, we describe two patients who developed brain metastases from HNSCC. Both patient tumors had p16INK4a overexpression, suggesting these tumors were HPV+. This was confirmed after PCR, in situ hybridization, and mass spectrometry detected the presence of HPV type 16 (HPV16) DNA, RNA and protein. To further characterize the presence of HPV16, we used a target enrichment strategy on tumor DNA and RNA to isolate the viral sequences from the brain metastases. Analysis by targeted next generation sequencing revealed that both tumors had the HPV genome integrated into the host genome at known hotspots, 8q24.21 and 14q24.1. Applying a similar target enrichment strategy to a larger cohort of HPV+ HNSCC brain metastases could help to identify biomarkers that can predict metastasis and/or identify novel therapeutic options.

Phosphorylation within the bipartite NLS alters the localization and toxicity of the ER stress response factor DDIT3/CHOP.

Regulated nuclear-cytoplasmic trafficking is a well-established mechanism utilized by cells to regulate adaptive and maladaptive responses to acute oxidant stress. Commonly associated with endoplasmic reticulum stress, the bZIP transcription factor CCAAT/enhancer-binding protein homologous protein (CHOP/DDIT3) mediates the cellular response to redox stress with effects on cellular growth, differentiation, and survival. We show through functional analyses that CHOP contains a conserved, compound pat4/bipartite nuclear localization signal within the basic DNA-binding domain. Using phylogenetic analyses and mass spectrometry, we now show that Ser107 located within the linker region of the bipartite NLS domain is a substrate for phosphorylation under standard culture conditions. Studies using the S107E phospho-mimic of CHOP indicate that changes in the charge properties at this residue regulate CHOP's nuclear-to-cytoplasmic ratio. And while co-stimulation with the SERCA inhibitor thapsigargin induced injury in cells expressing wild-type CHOP, the S107A point-mutant blocked this response. These findings indicate that phosphorylation within the bipartite NLS exerts regulatory effects on both the subcellular localization and toxic potential of DDIT3/CHOP. Future studies geared towards defining the relevant kinase/phosphatase networks that converge on the phosphorylation-regulated NLS (prNLS) phosphoepitope may provide an opportunity to constrain cellular damage in the context of acute ER stress.

Designing yeast as plant-like hyperaccumulators for heavy metals.

Hyperaccumulators typically refer to plants that absorb and tolerate elevated amounts of heavy metals. Due to their unique metal trafficking abilities, hyperaccumulators are promising candidates for bioremediation applications. However, compared to bacteria-based bioremediation systems, plant life cycle is long and growing conditions are difficult to maintain hindering their adoption. Herein, we combine the robust growth and engineerability of bacteria with the unique waste management mechanisms of plants by using a more tractable platform-the common baker's yeast-to create plant-like hyperaccumulators. Through overexpression of metal transporters and engineering metal trafficking pathways, engineered yeast strains are able to sequester metals at concentrations 10-100 times more than established hyperaccumulator thresholds for chromium, arsenic, and cadmium. Strains are further engineered to be selective for either cadmium or strontium removal, specifically for radioactive Sr90. Overall, this work presents a systematic approach for transforming yeast into metal hyperaccumulators that are as effective as their plant counterparts.

CMTM6 overexpression is associated with molecular and clinical characteristics of malignancy and predicts poor prognosis in gliomas.

CMTM6, a previously uncharacterized protein, was identified as a critical regulator of PD-L1, which is reported as an immune checkpoint inhibitor, to modulate the T cell activities both in vitro and in vivo of other tumors. However, the role of CMTM6 has so far remained unclear in glioma. To investigate the role of CMTM6 in gliomas, we analyzed the transcriptome level, genomic profiles and its relationship with clinical practice. 1862 glioma samples with transcriptome data were enrolled in this study, including CGGA RNA-seq, TCGA RNA-seq, CGGA-microarray, GSE16011 and IVY GBM databases. Clinical information and genomic profiles containing somatic mutations and DNA copy numbers were also obtained. We found that CMTM6 expression was highly correlated with major clinical and molecular characteristics. Cases with high CMTM6 expression were more likely to be predicted as malignant entities and frequent with genomic aberrations of driver oncogenes. Moreover, gene ontology analysis based on significantly correlated genes of CMTM6 expression exhibited that CMTM6 was associated with immune responses and inflammatory activities. CMTM6 was synthetic with other immune checkpoint inhibitors. Additionally, CMTM6 was involved in immune functions via modulating T-lymphocyte-mediated anti-tumor immunity. Finally, high CMTM6 expression was associated with reduced survival time and may serve as a strong indicator of poor prognosis in gliomas. In brief, High level of CMTM6 expression is closely related to high malignant gliomas. Meanwhile, CMTM6 plays an important role in regulating T cell activation and antitumor responses. Therefore, CMTM6 is a promising target for developing immunotherapy of gliomas.

Effects of DHA on Hippocampal Autophagy and Lysosome Function After Traumatic Brain Injury.

Traumatic brain injury (TBI) triggers endoplasmic reticulum (ER) stress and impairs autophagic clearance of damaged organelles and toxic macromolecules. In this study, we investigated the effects of the post-TBI administration of docosahexaenoic acid (DHA) on improving hippocampal autophagy flux and cognitive functions of rats. TBI was induced by cortical contusion injury in Sprague-Dawley rats, which received DHA (16 mg/kg in DMSO, intraperitoneal administration) or vehicle DMSO (1 ml/kg) with an initial dose within 15 min after the injury, followed by a daily dose for 3 or 7 days. First, RT-qPCR reveals that TBI induced a significant elevation in expression of autophagy-related genes in the hippocampus, including SQSTM1/p62 (sequestosome 1), lysosomal-associated membrane proteins 1 and 2 (Lamp1 and Lamp2), and cathepsin D (Ctsd). Upregulation of the corresponding autophagy-related proteins was detected by immunoblotting and immunostaining. In contrast, the DHA-treated rats did not exhibit the TBI-induced autophagy biogenesis and showed restored CTSD protein expression and activity. T2-weighted images and diffusion tensor imaging (DTI) of ex vivo brains showed that DHA reduced both gray matter and white matter damages in cortical and hippocampal tissues. DHA-treated animals performed better than the vehicle control group on the Morris water maze test. Taken together, these findings suggest that TBI triggers sustained stimulation of autophagy biogenesis, autophagy flux, and lysosomal functions in the hippocampus. Swift post-injury DHA administration restores hippocampal lysosomal biogenesis and function, demonstrating its therapeutic potential.

ER stress and impaired autophagy flux in neuronal degeneration and brain injury.

Autophagy is a highly controlled lysosome-mediated function in eukaryotic cells to eliminate damaged or aged long-lived proteins and organelles. It is required for restoring cellular homeostasis in cell survival under multiple stresses. Autophagy is known to be a double-edged sword because too much activation or inhibition of autophagy can disrupt homeostatic degradation of protein and organelles within the brain and play a role in neuronal cell death. Many factors affect autophagy flux function in the brain, including endoplasmic reticulum (ER) stress, oxidative stress, and aging. Newly emerged research indicates that altered autophagy flux functionality is involved in neurodegeneration of the aged brain, chronic neurological diseases, and after traumatic and ischemic brain injuries. In search to identify neuroprotective agents that may reduce oxidative stress and stimulate autophagy, one particular neuroprotective agent docosahexaenoic acid (DHA) presents unique functions in reducing ER and oxidative stress and modulating autophagy. This review will summarize the recent findings on changes of autophagy in aging, neurodegenerative diseases, and brain injury after trauma or ischemic strokes. Discussion of DHA functions is focused on modulating ER stress and autophagy in regard to its neuroprotection and anti-tumor functions.