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Harnessing the full power of nascent quantum processors requires the efficient management of a limited number of quantum bits with finite coherent lifetimes. Hybrid algorithms, such as the variational quantum eigensolver (VQE), leverage classical resources to reduce the required number of quantum gates. Experimental demonstrations of VQE have resulted in calculation of Hamiltonian ground states, and a new theoretical approach based on a quantum subspace expansion (QSE) has outlined a procedure for determining excited states that are central to dynamical processes. We use a superconducting-qubit-based processor to apply the QSE approach to the H_{2} molecule, extracting both ground and excited states without the need for auxiliary qubits or additional minimization. Further, we show that this extended protocol can mitigate the effects of incoherent errors, potentially enabling larger-scale quantum simulations without the need for complex error-correction techniques.

We experimentally and theoretically investigate the quantum trajectories of jointly monitored transmon qubits embedded in spatially separated microwave cavities. Using nearly quantum-noise-limited superconducting amplifiers and an optimized setup to reduce signal loss between cavities, we can efficiently track measurement-induced entanglement generation as a continuous process for single realizations of the experiment. The quantum trajectories of transmon qubits naturally split into low and high entanglement classes. The distribution of concurrence is found at any given time, and we explore the dynamics of entanglement creation in the state space. The distribution exhibits a sharp cutoff in the high concurrence limit, defining a maximal concurrence boundary. The most-likely paths of the qubits’ trajectories are also investigated, resulting in three probable paths, gradually projecting the system to two even subspaces and an odd subspace, conforming to a “half-parity” measurement. We also investigate the most-likely time for the individual trajectories to reach their most entangled state, and we find that there are two solutions for the local maximum, corresponding to the low and high entanglement routes. The theoretical predictions show excellent agreement with the experimental entangled-qubit trajectory data.

Cholecystectomy is one of the most performed surgical procedures. The safety of this surgery notwithstanding, the sheer volume of operations results in a notable incidence of post-cholecystectomy complications. Early and accurate diagnosis of such complications is essential for timely and effective management. Imaging techniques are critical for this purpose, aiding in distinguishing between expected postsurgical changes and true complications. This review highlights current knowledge on the indications for cholecystectomy, pertinent surgical anatomy and surgical technique, and the recognition of anatomical variants that may complicate surgery. The article also outlines the roles of various imaging modalities in identifying complications, the spectrum of possible postsurgical anatomical changes, and the implications of such findings. Furthermore, we explore the array of complications that can arise post-cholecystectomy, such as biliary system injuries, gallstone-related issues, vascular complications, and the formation of postsurgical collections. Radiologists should be adept at identifying normal and abnormal postoperative findings to guide patient management effectively., (© 2024. The Author(s).)

Pancreatic surgery is considered one of the most technically challenging surgical procedures, despite the evolution of modern techniques. Neoplasms remain the most common indication for pancreatic surgery, although inflammatory conditions may also prompt surgical evaluation. The choice of surgical procedure depends on the type and location of the pathologic finding because different parts of the pancreas have separate vascular supplies that may be shared by adjacent organs. The surgical approach could be conventional or minimally invasive (laparoscopic, endoscopic, or robotic assisted). Because of the anatomic complexity of the pancreatic bed, perioperative complications may be frequently encountered and commonly involve the pancreatic-biliary, vascular, lymphatic, or bowel systems, irrespective of the surgical technique used. Imaging plays an important role in the assessment of suspected postoperative complications, with CT considered the primary imaging modality, while MRI, digital subtraction angiography, and molecular imaging are considered ancillary diagnostic tools. Accurate diagnosis of postoperative complications requires a solid understanding of pancreatic anatomy, surgical indications, normal postoperative appearance, and expected postsurgical changes. The practicing radiologist should be familiar with the most common perioperative complications, such as anastomotic leak, abscess, and hemorrhage, and be able to differentiate these entities from normal anticipated postoperative changes such as seroma, edema and fat stranding at the surgical site, and perivascular soft-tissue thickening. In addition to evaluation of the primary operative fossa, imaging plays a fundamental role in assessment of the adjacent organ systems secondarily affected after pancreatic surgery, such as vascular, biliary, and enteric complications. Published under a CC BY 4.0 license. Test Your Knowledge questions are available in the supplemental material. See the invited commentary by Winslow in this issue.

Intensive care units (ICUs) may disrupt sleep. Quantitative ICU studies of concurrent and continuous sound and light levels and timings remain sparse in part due to the lack of ICU equipment that monitors sound and light. Here, we describe sound and light levels across three adult ICUs in a large urban United States tertiary care hospital using a novel sensor. The novel sound and light sensor is composed of a Gravity Sound Level Meter for sound level measurements and an Adafruit TSL2561 digital luminosity sensor for light levels. Sound and light levels were continuously monitored in the room of 136 patients (mean age = 67.0 (8.7) years, 44.9% female) enrolled in the Investigation of Sleep in the Intensive Care Unit study (ICU-SLEEP; Clinicaltrials.gov: #NCT03355053), at the Massachusetts General Hospital. The hours of available sound and light data ranged from 24.0 to 72.2 hours. Average sound and light levels oscillated throughout the day and night. On average, the loudest hour was 17:00 and the quietest hour was 02:00. Average light levels were brightest at 09:00 and dimmest at 04:00. For all participants, average nightly sound levels exceeded the WHO guideline of < 35 decibels. Similarly, mean nightly light levels varied across participants (minimum: 1.00 lux, maximum: 577.05 lux). Sound and light events were more frequent between 08:00 and 20:00 than between 20:00 and 08:00 and were largely similar on weekdays and weekend days. Peaks in distinct alarm frequencies (Alarm 1) occurred at 01:00, 06:00, and at 20:00. Alarms at other frequencies (Alarm 2) were relatively consistent throughout the day and night, with a small peak at 20:00. In conclusion, we present a sound and light data collection method and results from a cohort of critically ill patients, demonstrating excess sound and light levels across multiple ICUs in a large tertiary care hospital in the United States. ClinicalTrials.gov, #NCT03355053. Registered 28 November 2017, https://clinicaltrials.gov/ct2/show/NCT03355053.

Using observational data and variation in hospital admissions across days of the week, we examined the association between ED boarding time and development of delirium within 72 hours of admission among patients aged 65+ years admitted to an inpatient neurology ward. We exploited a natural experiment created by potentially exogenous variation in boarding time across days of the week because of competition for the neurology floor beds. Using proportional hazard models adjusting for socio-demographic and clinical characteristics in a propensity score, we examined the time to delirium onset among 858 patients: 2/3 were admitted for stroke, with the remaining admitted for another acute neurologic event. Among all patients, 81.2% had at least one delirium risk factor in addition to age. All eligible patients received delirium prevention protocols upon admission to the floor and received at least one delirium screening event. While the clinical and social-demographic characteristics of admitted patients were comparable across days of the week, patients with ED arrival on Sunday or Tuesday were more likely to have had delayed floor admission (waiting time greater than 13 hours) and delirium (adjusted HR = 1.54, 95%CI:1.37-1.75). Delayed initiation of delirium prevention protocol appeared to be associated with greater risk of delirium within the initial 72 hours of a hospital admission.

Sleep is a biological mandate with an integral role in optimizing functions that maintain psychological and physical health. During critical illness, however, sleep may be disrupted at best and elusive at worst. Sleep improvement efforts and research endeavors evaluating interventions to improve sleep in critically ill adults are hampered by limited methods available to measure sleep in this setting. This narrative review summarizes available modalities for sleep assessment in the ICU, describes new ICU sleep assessment methods under development, and highlights features of the ideal ICU sleep measurement tool., Data Sources: The most relevant literature and author experiences were assessed for inclusion from PubMed and textbooks., Study Selection: The authors selected studies for inclusion by consensus., Data Extraction: The authors reviewed each study and selected appropriate data for inclusion by consensus., Data Synthesis: Currently available tools to measure sleep in critically ill adults have important flaws. Subjective measurements are limited by recall bias, the inability of many patients to communicate, and poorly correlate with objective measures when completed by surrogates. Actigraphy does not consider the effects of sedating medications or myopathy leading to an over estimation of sleep time. Polysomnography, the gold standard for sleep assessment, is limited by interpretation issues and practical application concerns. Single and multiple channel electroencephalogram devices offer real-time physiologic data and are more practical to use than polysomnography but are limited by the scope of sleep-specific information they can measure and poorly characterize the circadian system., Conclusions: A measurement tool that offers real-time sleep and circadian assessment and is practical for broad application in the ICU does not exist. Newer sleep assessment devices have shown promise in measuring physiologic data in real time; when used in combination with other assessment modalities, and analyzed by computational techniques, they may revolutionize sleep monitoring in the ICU., Competing Interests: Dr. Devlin has received funding from the National Institute of Aging, the Canadian Institute of Health Research, and Bioexcel Therapeutics; he is on the editorial board of Critical Care Medicine. Dr. Kimchi has received funding from the National Institute of Mental Health. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Over- and under-sedation are common in the ICU, and contribute to poor ICU outcomes including delirium. Behavioral assessments, such as Richmond Agitation-Sedation Scale (RASS) for monitoring levels of sedation and Confusion Assessment Method for the ICU (CAM-ICU) for detecting signs of delirium, are often used. As an alternative, brain monitoring with electroencephalography (EEG) has been proposed in the operating room, but is challenging to implement in ICU due to the differences between critical illness and elective surgery, as well as the duration of sedation. Here we present a deep learning model based on a combination of convolutional and recurrent neural networks that automatically tracks both the level of consciousness and delirium using frontal EEG signals in the ICU. For level of consciousness, the system achieves a median accuracy of 70% when allowing prediction to be within one RASS level difference across all patients, which is comparable or higher than the median technician-nurse agreement at 59%. For delirium, the system achieves an AUC of 0.80 with 69% sensitivity and 83% specificity at the optimal operating point. The results show it is feasible to continuously track level of consciousness and delirium in the ICU., Competing Interests: Competing interestsThe authors declare no competing interests.

Background: Postoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up., Methods: This study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method-based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months., Results: One hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small (r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07-1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72-1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71-2.09)., Conclusions: Delirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.

Circulating tumor cells (CTCs) are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X) from blood of melanoma patients using a simple centrifugation device (OncoQuick), and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF) were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively) compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001). There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001), and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50%) stained for both pan-cytokeratin (KRT) markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14). Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA) may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs). The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids, and their role in metastatic progression.

Evaluation of: Lorenzen S, Brücher B, Zimmermann F et al.: Neoadjuvant continuous infusion of weekly 5-fluorouracil and excalating doses of oxaliplatin plus concurrent radiation in locally advanced oesophageal squamous cell carcinoma: results of a Phase I/II trial. Br. J. Cancer 99, 1020-1026 (2008). In this article, we summarize Lorenzen's study and briefly describe some of the landmark studies in preoperative chemoradiation in both squamous cell carcinoma and adenocarcinoma of the esophagus. Incorporation of oxaliplatin into the neoadjuvant regimen has been reported by several groups. The results of histological response varied from study to study. Lorenzen and colleagues reported a reasonably high histological response rate with very manageable toxicities in squamous cell carcinoma of the esophagus. However, as we know, squamous cell carcinoma is generally more responsive to chemoradiation. Future studies may be warranted to assess the efficacy of this regimen in a larger cohort. Nonetheless, in the era of targeted therapy, addition of targeted agents to future preoperative chemoradiation regimens should be considered. At present time, the result of RTOG Phase III study integrating cetuximab in the preoperative regimen is awaited.

Introduction: Over the last several decades, the incidence of gastroesophageal junction tumors has been increasing. Often, patients present late in the course of their disease. However, if the disease is localized, then complete surgical resection remains the standard of cure and the best chance for cure. On occasion, these tumors involve a significant portion of both the distal esophagus and proximal stomach., Materials and Methods: In order to completely remove these tumors with an adequate surgical margin and lymph node dissection, a total gastrectomy and total esophagectomy with colonic interposition may be required. We have utilized this approach on six patients with excellent clinical results. In this manuscript, we discuss the technical considerations involved in this approach and present our results.

Background: The gastroesophageal junction was commonly approached surgically through a thoracoabdominal incision. With the advent of improved retraction devices, this has been abandoned because the upper midline incision has provided adequate exposure with decreased morbidity. However, exposure of the gastroesophageal junction remains a challenge in the setting of surgical complications associated with repeat surgeries and abscess formation., Methods: Patients were placed in the right lateral decubitus position. An incision was made 2 cm below the tip of the scapula to a point in the midline equidistant from the xiphoid process to the umbilicus. The chest was entered at the eighth intercostal space. The abdominal cavity was entered by dividing the diaphragm peripherally from its lateral attachments to the ribs., Results: We have used this approach on 4 patients. All patients were discharged home tolerating oral diets. The average postoperative stay was 10 days. No complications related to the incision were reported. At the 6-month follow-up evaluation all patients continued to tolerate a regular diet without difficulties., Conclusions: The technique described allows for excellent exposure of the upper gastrointestinal tract in a subset of patients with complex upper gastrointestinal complications.

Background: The discovery of the c-KIT mutation and the advent of targeted drug therapy with imatinib mesylate have revolutionized the management of gastrointestinal stromal tumors (GISTs). The outcome of patients with surgically treated GISTs treated in the era of targeted drug therapy was assessed and factors associated with adverse outcomes determined., Materials and Methods: Patients with GISTs requiring surgery at a tertiary care center from 2002 to 2007 were reviewed and prognostic factors determined., Results: Forty patients were surgically treated for GISTs. The median age at presentation was 59 years. The stomach (55%) was the main site of primary disease. The median tumor size was 7 cm. Eleven (28%) patients had metastatic disease at presentation. Surgery was undertaken in all patients with curative intent. Multi-organ resection was required in 10 (25%) patients. Imatinib mesylate was administered postoperatively in 68% of cases. Median follow-up was 24 months. There was a 40% recurrence rate with 63% undergoing repeat surgical resection. The peritoneum and liver were the main sites of recurrent disease. The 5-year disease-specific survival and disease-free survival (DFS) were 65% and 35%, respectively. High mitotic rate (P = 0.017) and tumor size greater than 10 cm (P = 0.009) were the only prognostically significant adverse factors of DFS on multivariate analysis, independent of imatinib mesylate treatment., Conclusion: Aggressive surgical treatment and follow-up of GISTs, combined with targeted drug therapy, leads to long-term DFS survival. Tumor recurrence is independently associated with a high tumor mitotic rate and size greater than 10 cm, despite the use of adjuvant targeted drug therapy.

Improvements in the understanding of molecular oncogenesis and mechanisms of drug resistance have presented new opportunities for the treatment of gastrointestinal stromal tumors (GIST). In particular, the discovery of c-kit genomic mutations in GIST and the development of targeted therapy with imatinib mesylate and sunitinib have heralded a new era in the treatment of this disease. Due to its high activity in GIST, imatinib has become the standard of care in treating both advanced disease and localized disease with high-risk features. On the other hand, these developments have provided new challenges in optimizing the use of our drug armamentarium in conjunction with surgery. This review focuses on the molecular oncogenesis of GIST and provides a summary of recent approaches in the management of this disease.

Purpose: Invasion of the superior mesenteric vein (SMV) or superior mesenteric-portal vein (SMPV) confluence, in pancreatic adenocarcinoma of the head and uncinate process, is the most common unexpected finding at the time of pancreaticoduodenectomy. Resection of the SMV or SMPV with reconstruction using autologous and synthetic conduits is well established. We describe the use of the left renal vein as a practical, easy, and durable alternative as an interposition graft after pancreaticoduodenectomy with en bloc segmental resection of the SMV., Methods and Results: Involvement of the SMV by a pancreatic mass is resected en bloc with a standard pancreaticoduodenectomy. The left renal vein is then harvested from the junction with the IVC and proximal to the adrenal vein. This is then used as a vein graft for the resected portion of the SMV., Discussion: Complete pancreatic cancer resection with grossly tumor-free margins provides the only chance for long-term cure. Isolated tumor involvement of the SMV or SMPV confluence is not associated with histopathological variables predictive of a poor prognosis and appears to be a function of tumor location rather than an indicator of biological aggressiveness. Recurrence and long-term survival following pancreaticoduodenectomy with and without vein resection are equivalent, provided grossly negative margins are achieved. We describe the use of the left renal vein as a technically feasible, easy, and durable conduit for SMV reconstruction in pancreaticoduodenectomy. After resection of the left renal vein, significant increase in postoperative serum creatinine has not been reported; collateral flow has been confirmed by radiological methods and severe renal dysfunction perioperatively, postoperatively, and during long-term follow-up has not been observed.

We examined the interaction between forphenicinol (FPL) and cyclophosphamide (CPA) or ionizing radiation (IR) on the growth of murine squamous cell carcinoma tumors SCCVII. Primary tumors were established in C3H mice by injecting SCCVII tumor cells subcutaneously into the right hind limb. FPL (100 mg/kg for 8 days) and/or CPA (25 mg/kg twice) were administered by intraperitoneal injection. Tumors were irradiated to a total dose of 40 Gy (eight 5-Gy fractions). SCCVII tumor growth was inhibited by FPL (P=0.054), IR (P=0.003) and CPA (P<0.001) compared with control. The combination of FPL and CPA inhibited tumor growth additively compared with either treatment alone in both small- and large-volume tumors. FPL did not significantly enhance the antitumor effects of IR, however, when CPA+FPL were combined with IR, significant tumor growth inhibition was observed compared with FPL alone (P<0.001), CPA alone (P=0.002) and IR alone (P=0.002). Due to its low toxicity profile, FPL may be combined with CPA, IR and other cytotoxic therapies to potentially enhance the therapeutic ratio.

The underlying pathophysiological processes of amyloid angiopathy have been difficult to study because the vessel size affected is too smallfor imaging in the human condition, and animal models have not yet been adequately developed or characterized. Herein we present characterization of animal models of overexpression of the human AbetaPP gene, initially developed as models of Alzheimer's disease, but which fortuitously also develop marked cerebral amyloid angiopathy. We also present a novelform of microscopy that allows in vivo imaging of vessels affected by amyloid in the anesthetized, but intact, animal.