The Lymphoma Epidemiology of Outcomes cohort study: Design, baseline characteristics, and early outcomes.

To address the current and long-term unmet health needs of the growing population of non-Hodgkin lymphoma (NHL) patients, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/). A total of 7735 newly diagnosed patients aged 18 years and older with NHL were prospectively enrolled from 7/1/2015 to 5/31/2020 at 8 academic centers in the United States. The median age at diagnosis was 62 years (range, 18-99). Participants came from 49 US states and included 538 Black/African-Americans (AA), 822 Hispanics (regardless of race), 3386 women, 716 age <40 years, and 1513 rural residents. At study baseline, we abstracted clinical, pathology, and treatment data; banked serum/plasma (N = 5883, 76.0%) and germline DNA (N = 5465, 70.7%); constructed tissue microarrays for four major NHL subtypes (N = 1189); and collected quality of life (N = 5281, 68.3%) and epidemiologic risk factor (N = 4489, 58.0%) data. Through August 2022, there were 1492 deaths. Compared to population-based SEER data (2015-2019), LEO participants had a similar distribution of gender, AA race, Hispanic ethnicity, and NHL subtype, while LEO was underrepresented for patients who were Asian and aged 80 years and above. Observed overall survival rates for LEO at 1 and 2 years were similar to population-based SEER rates for indolent B-cell (follicular and marginal zone) and T-cell lymphomas, but were 10%-15% higher than SEER rates for aggressive B-cell subtypes (diffuse large B-cell and mantle cell). The LEO cohort is a robust and comprehensive national resource to address the role of clinical, tumor, host genetic, epidemiologic, and other biologic factors in NHL prognosis and survivorship.

Characterization of Extracellular Vesicles by Resistive-Pulse Sensing on In-Plane Multipore Nanofluidic Devices.

Extracellular vesicles (EVs) are cell-derived, naturally produced, membrane-bound nanoscale particles that are linked to cell-cell communication and the propagation of diseases. Here, we report the design and testing of in-plane nanofluidic devices for resistive-pulse measurements of EVs derived from bovine milk and human breast cancer cells. The devices were fabricated in plane with three nanopores in series to determine the particle volume and diameter, two pore-to-pore regions to measure the electrophoretic mobility and zeta potential, and an in-line filter to prevent cellular debris and aggregates from entering the nanopore region. Devices were tested with and without the channels coated with a short-chain PEG silane to minimize electroosmotic flow and permit an accurate measurement of the electrophoretic mobility and zeta potential of the EVs. To enhance throughput of EVs, vacuum was applied to the waste reservoir to increase particle frequencies up to 1000 min-1. The nanopores had cross-sections 200 nm wide and 200 nm deep and easily resolved EV diameters from 60 to 160 nm. EVs from bovine milk and human breast cancer cells had similar particle size distributions, but their zeta potentials differed by 2-fold, -8 ± 1 and -4 ± 1 mV, respectively.

Recurrent petit mal seizures in Erdheim-Chester disease mimicking an intra-axial brain tumor: illustrative case.

BACKGROUND: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized histologically by foamy histiocytes and Touton giant cells in a background of fibrosis. Bone pain with long bone osteosclerosis is highly specific for ECD. Central nervous system involvement is rare, although dural, hypothalamic, cerebellar, brainstem, and sellar region involvement has been described. OBSERVATIONS: A 59-year-old man with a history of ureteral obstruction, medically managed petit mal seizures, and a left temporal lesion followed with serial magnetic resonance imaging (MRI) presented with worsening seizure control. Repeat MRI identified bilateral amygdala region lesions. Gradual growth of the left temporal lesion over 1 year with increasing seizure frequency prompted resection. A non-Langerhans cell histiocytosis with a BRAF V600E mutation was identified on pathology. Imaging findings demonstrated retroperitoneal fibrosis and long bone osteosclerosis with increased fluorodeoxyglucose uptake that, together with the neuropathologic findings, were diagnostic of ECD. LESSONS: This case of biopsy-proven ECD is unique in that the singular symptom was seizures well controlled with medical management in the presence of similarly located bilateral anterior mesial temporal lobe lesions. Although ECD is rare intracranially, its variable imaging presentation, including the potential to mimic seizure-associated medial temporal lobe tumors, emphasizes the need for a wide differential diagnosis.

Amaryllidaceae Alkaloids Decrease the Proliferation, Invasion, and Secretion of Clinically Relevant Cytokines by Cultured Human Colon Cancer Cells.

Alkaloids isolated from members of the Amaryllidaceae plant family are promising anticancer agents. The purpose of the current study was to determine if the isocarbostyrils narciclasine, pancratistatin, lycorane, lycorine, crinane, and haemanthamine inhibit phenomena related to cancer progression in vitro. To achieve this, we examined the proliferation, adhesion, and invasion of cultured human colon cancer cells via MTT assay and Matrigel-coated Boyden chambers. In addition, Luminex assays were used to quantify the secretion of matrix metalloproteinases (MMP) and cytokines associated with poor clinical outcomes. We found that all alkaloids decreased cell proliferation regardless of TP53 status, with narciclasine exhibiting the greatest potency. The effects on cell proliferation also appear to be specific to cancer cells. Narciclasine, lycorine, and haemanthamine decrease both adhesion and invasion but with various potencies depending on the cell line. In addition, narciclasine, lycorine, and haemanthamine decreased the secretion of MMP-1, -2, and -7, as well as the secretion of the cytokines pentraxin 3 and vascular endothelial growth factor. In conclusion, the present study shows that Amaryllidaceae alkaloids decrease phenomena and cytokines associated with colorectal cancer progression, supporting future investigations regarding their potential as multifaceted drug candidates.

Comparative Analysis of LASIK Flap Diameter and its Centration Using Two Different Femtosecond Lasers.

The aim of this study was to compare the diameter, accuracy, variability, and centration with respect to the limbus of corneal flaps created by two femtosecond lasers, the VisuMax, and Wavelight FS200, for laser in situ keratomileusis (LASIK) and how these flaps affect visual outcomes. This is a retrospective chart review of flap morphology created during LASIK Surgery. Overall, 168 eyes underwent flap creation using the WaveLight FS200 laser, and on 189 eyes, the VisuMax laser was used. Of these total number, flap morphology was analyzed in a random sample of 158 eyes; 80 with the Visumax laser and 78 with the WaveLight FS200 laser. Intraoperative photos of the flaps taken by the Wavelight Allegretto EX500 were analyzed. Flap diameters and centration were measured using Adobe Acrobat Pro. All patients had visual acuity measurements including uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent refraction (SE) and refractive astigmatism recorded three months postoperatively. Greater than 90% of patients in both groups achieved a UDVA of 20/20 postoperatively. The mean difference between targeted and achieved flap diameter was 0.50 +/- 0.15 mm in the VisuMax group and 0.35 +/- 0.15 millimeters (mm) in the FS200 group (P<0.01). The flap diameters of the VisuMax group were more precise with a variance of 0.024 mm compared to a variance of 0.038 mm in the FS200 group (P<0.05). VisuMax flaps were more nasally displaced (log(NA/TA) = -0.21 +/- 0.10 mm) compared to the FS200 flaps (log(NA/TA) = 0.03 +/- 0.10 mm), (P< 0.01). We concluded that both the VisuMax and FS200 created flaps larger than the preoperative targeted diameter. VisuMax created corneal flaps that had a greater degree of deviation from the targeted diameter when compared to flaps from the FS200. However, there was less variance in the VisuMax flap diameter. In addition, VisuMax flaps were more nasally displaced. There were no statistically significant differences in visual outcomes when comparing the two femtosecond lasers.

Enantioselective Synthesis of Isocarbostyril Alkaloids and Analogs Using Catalytic Dearomative Functionalization of Benzene.

Enantioselective total syntheses of the anticancer isocarbostyril alkaloids (+)-7-deoxypancratistatin, (+)-pancratistatin, (+)-lycoricidine, and (+)-narciclasine are described. Our strategy for accessing this unique class of natural products is based on the development of a Ni-catalyzed dearomative trans-1,2-carboamination of benzene. The effectiveness of this dearomatization approach is notable, as only two additional olefin functionalizations are needed to construct the fully decorated aminocyclitol cores of these alkaloids. Installation of the lactam ring has been achieved through several pathways and a direct interconversion between natural products was established via a late-stage C-7 cupration. Using this synthetic blueprint, we were able to produce natural products on a gram scale and provide tailored analogs with improved activity, solubility, and metabolic stability.

Synthesis of (+)-Pancratistatins via Catalytic Desymmetrization of Benzene.

A concise synthesis of (+)-pancratistatin and (+)-7-deoxypancratistatin from benzene using an enantioselective, dearomative carboamination strategy has been achieved. This approach, in combination with the judicious choice of subsequent olefin-type difunctionalization reactions, permits rapid and controlled access to a hexasubstituted core. Finally, minimal use of intermediary steps as well as direct, late stage C-7 hydroxylation provides both natural products in six and seven operations.

Analysing the operative experience of basic surgical trainees in Ireland using a web-based logbook.

BACKGROUND: There is concern about the adequacy of operative exposure in surgical training programmes, in the context of changing work practices. We aimed to quantify the operative exposure of all trainees on the National Basic Surgical Training (BST) programme in Ireland and compare the results with arbitrary training targets. METHODS: Retrospective analysis of data obtained from a web-based logbook (http://www.elogbook.org) for all general surgery and orthopaedic training posts between July 2007 and June 2009. RESULTS: 104 trainees recorded 23,918 operations between two 6-month general surgery posts. The most common general surgery operation performed was simple skin excision with trainees performing an average of 19.7 (± 9.9) over the 2-year training programme. Trainees most frequently assisted with cholecystectomy with an average of 16.0 (± 11.0) per trainee. Comparison of trainee operative experience to arbitrary training targets found that 2-38% of trainees achieved the targets for 9 emergency index operations and 24-90% of trainees achieved the targets for 8 index elective operations. 72 trainees also completed a 6-month post in orthopaedics and recorded 7,551 operations. The most common orthopaedic operation that trainees performed was removal of metal, with an average of 2.90 (± 3.27) per trainee. The most common orthopaedic operation that trainees assisted with was total hip replacement, with an average of 10.46 (± 6.21) per trainee. CONCLUSIONS: A centralised web-based logbook provides valuable data to analyse training programme performance. Analysis of logbooks raises concerns about operative experience at junior trainee level. The provision of adequate operative exposure for trainees should be a key performance indicator for training programmes.

Training on N.O.T.E.S.: from history we learn.

Surgical errors occurring early in the learning curve of laparoscopic surgery providers delayed the uptake and progress of minimally invasive surgery (MIS) for years. This taught us a valuable lesson; innovations in surgical techniques should not be rapidly implemented until all aspects including applicability, feasibility and safety have been fully tested. In 2005, the Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR) published a white paper highlighting the barriers to NOTES development and identifying key elements for its progress. One of these elements is the training of future providers. Proficiency-based, virtual reality simulation will offer a feasible alternative to animal testing once the safety and efficacy parameters of NOTES are established. Recent advances in imaging including computed tomography (CT) scanning, magnetic resonance imaging (MRI) scanning, and ultrasound (US) scanning can offer improved image registration and real-time tracking. Combining these advanced imaging technologies with the newly designed virtual reality simulators will result in a fully comprehensive simulation curriculum which will offer a unique facility for future NOTES providers to train anytime, anywhere, and as much as they need to in order to achieve the pre-set proficiency levels for a variety of NOTES procedures. Furthermore they will incorporate patient-specific anatomical models obtained from patient imaging and uploaded onto the simulator to ensure face reliability and validity assurance. Training in a clean, safe environment with proximate feedback and performance analysis will help accelerate the learning curve and therefore improve patients' safety and outcomes in order to maximize the benefits of innovative access procedures such as NOTES.

N.O.T.E.S.: the progression of a novel and emerging technique.

Natural Orifice Transluminal Endoscopic Surgery (NOTES) is the latest and perhaps most significant innovation in surgery since Phillipe Mouret of France performed the first laparoscopic cholecystectomy in 1987. This new "minimum-invasive" concept that promises scar-free surgery is steadily gathering momentum. It is another milestone in our quest to eliminate surgical trauma, speed patient recovery time and decrease surgical wound-related complications. On 22 July 2005, the Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR) published a white paper highlighting the barriers to NOTES development, which included the need for appropriate selection of access points, effective closure of the enterotomy site, innovative tools, stable platforms and improved endoscopic orientation. These are just some of the many issues that need to be resolved before the NOTES concept and technique could become a common feature of modern surgery. The publication of the white paper ushered in the beginning of multiple research projects using animal models to test the application of NOTES and its newly developed instruments. The success in animal models was followed by several highly selected successful human trials. National and international surgical innovation departments should now be created where medical industry personnel including inventors, designers and engineers can work together with the medical and surgical providers to address all the limitations affecting NOTES progress.

Patients' recall of clinical information following laparoscopy for acute abdominal pain.

BACKGROUND: Failures in doctor-patient communication and patients' understanding continue to confound improvements in the delivery of quality healthcare. In the context of acute abdominal pain managed by means of laparoscopy, it was hypothesized that patients are either not adequately informed, or do not reliably retain simple relevant information transmitted at the time of the procedure. This study was designed to evaluate the reliability of information transfer between doctor and patient in this setting, including the diagnosis and whether or not the appendix was removed. METHODS: A retrospective study of 350 consecutive patients who had undergone laparoscopy for acute abdominal pain over 3.5 years was designed. Each patient completed a telephone questionnaire that was used to evaluate the accuracy of patients' information. RESULTS: In total, 26.9 per cent of patients did not know or were incorrect regarding the surgical procedure performed. Similarly, 20.0 per cent of all patients did not know or were incorrect regarding the status of their appendix after surgery and 30.0 per cent of patients were incorrect regarding the diagnosis. Despite all of these statistics, 91.4 per cent of patients were happy with the information they had received regarding the procedure. CONCLUSION: Some 26.9 per cent of patients who underwent laparoscopy for acute abdominal pain were incorrect or did not know about the procedure that had been performed. This could lead to a further unnecessary operation should they re-present with similar symptoms.

Minimally invasive techniques in common surgical procedures: implications for training.

BACKGROUND: Laparoscopic techniques are increasingly used in common surgical procedures. Many of these procedures are used to teach basic surgical trainees (BST) and therefore introduction of these techniques may have implications for training. AIMS: To establish whether the introduction of laparoscopic techniques reduced the opportunity of BSTs to perform surgical procedures. METHODS: Patients undergoing hernia repair or appendicectomy in 1991 (when laparoscopy was first introduced) and 1997 (when laparoscopy was readily available) were identified using the Hospital In-Patient Enquiry (HIPE) database. The principal operator and whether the procedure was open or laparoscopic were identified by chart review. RESULTS: The data showed a 50% reduction in the number of appendicectomies performed by BSTs following the introduction of laparoscopic techniques. The number of hernia repairs performed by BSTs has been preserved but the proportion by BSTs fell from 10 to 6%. The proportion of BST-performed procedures carried out laparoscopically has been reduced compared with the registrar-performed group. CONCLUSIONS: The use of minimally invasive techniques has had a negative effect on surgical training. Appropriate measures must be taken to minimise this and such measures should include a structured approach to laparoscopic training and greater access to laparoscopic training facilities.

Changing trends in the management of gallstone disease.

BACKGROUND: Day case cholecystectomy is increasingly becoming a management option for elective cases while "same admission" cholecystectomy is now considered a favorable option in the treatment of acute cholecystitis. To assess the advent of these changes in our surgical practice, a retrospective analysis of our experience is presented. METHODS: All patients undergoing cholecystectomy between January 2000 and January 2001 were analyzed according to admission status, operation type, conversion rate, complications, and nonsurgical intervention. RESULTS: 156 patients underwent cholecystectomy and 152 charts were retrieved. Laparoscopic cholecystectomy was performed on 95% of patients with a conversion rate of 9%. Morbidity for the series was 12.5%, including one common bile duct injury (0.6%). Day case and acute cholecystectomy comprised 67% of our cholecystectomy practice. CONCLUSIONS: Our findings suggest that there is an increasing trend toward shortening the hospital stay of patients undergoing laparoscopic cholecystectomy. This does not appear to have had a deleterious effect on outcome.

Construction of phosphatidylethanolamine-less strain of Saccharomyces cerevisiae. Effect on amino acid transport.

A triple yeast mutant was constructed which lacks BST1, the gene for sphingosine lyase, besides the phosphatidylserine decarboxylases PSD1 and PSD2. In this yeast mutant, which can only be grown in the presence of exogenous ethanolamine, phosphatidylethanolamine can be depleted to very low levels. Under those conditions, respiration as well as glucose and 3-O-methylglucose uptake proceed unaffected. Plasma membrane ATPase is as active in these cells as that of control cells grown in the presence of ethanolamine. Drastically decreased, however, are H+/amino acid symporters. The activities of arginine (Can1p), proline (Put4p) and general amino acid permease (Gap1p) are decreased more than 20-fold. Amino acid transport in yeast is dependent on coupling to the proton motive force. It can be envisaged that phosphatidylethanolamine might play a role in this process or in the early steps of the secretion pathway common for all amino acid permeases or, eventually, it could affect the transport proteins directly at the plasma membrane Transformation of the triple mutant with a CEN plasmid harbouring BST1 wild-type gene totally reversed its phenotype to that observed in the double mutant.

Should an appendix that looks 'normal' be removed at diagnostic laparoscopy for acute right iliac fossa pain?

OBJECTIVE: To find out whether the removal of the appendix from patients in whom laparoscopy for acute right iliac fossa pain shows no abnormality is justified to avoid the risk of missing acute appendicitis. PATIENTS: The records of patients who, between 1990 and 1997 had emergency laparoscopy for acute right iliac fossa pain were reviewed. Only those in whom laparoscopy had shown no abnormality and had not had the appendix removed were included in the study. METHODS: Outcome was assessed by telephone questionnaire to the patient, the general practitioner, or both. RESULTS: Emergency laparoscopy had been done for 254 patients. No abnormality was detected in 41. Full follow up was available on 34 patients (83%). 21 patients have remained entirely free of symptoms. Of the 13 patients who had recurrent symptoms, 2 subsequently had a histologically normal appendix removed, yet still had symptoms; 2 had a second laparoscopy that showed no abnormality; 5 had ultrasound; and 4 had colonoscopy or a barium enema examination. CONCLUSION: Removal of an appendix that looks 'normal' at emergency laparoscopy for right iliac fossa pain is unjustified.

Specialized intestinal metaplasia in patients with gastro-oesophageal reflux disease.

BACKGROUND: There is an increasing awareness that short (less than 3 cm) segments of Barrett's epithelium and macroscopically normal cardia epithelium may harbour specialized intestinal metaplasia (SIM), a premalignant phenotype. The prevalence of SIM was studied prospectively in an unselected population of patients attending for endoscopy, and the association of SIM with symptoms, lifestyle, medication, endoscopic oesophagitis and carditis was investigated. METHODS: Two hundred consecutive patients underwent endoscopy. Biopsies taken from just below the squamocolumnar junction were stained for SIM, and were analysed for carditis and Helicobacter pylori infection. A detailed questionnaire of symptoms, tobacco consumption and the use of proton pump inhibitors was completed. RESULTS: Forty-two patients (21 per cent) had SIM: 19 (15 per cent) of 126 in an endoscopically normal oesophagus, 15 (24 per cent) of 63 in a short segment of Barrett's epithelium and eight of 11 in classical Barrett's oesophagus. There was a significant association between SIM and carditis (P < 0.0001) and endoscopic oesophagitis (P = 0.03). CONCLUSION: SIM is prevalent in patients undergoing endoscopy, does not correlate with symptoms or H. pylori infection, but is significantly associated with endoscopic and pathological markers of gastro-oesophageal reflux.

Laparoscopic extraperitoneal inguinal hernia repair in the day-care setting.

BACKGROUND: Totally extraperitoneal (TEP) laparoscopic inguinal hernia repair is gaining popularity, and our preference is to perform this procedure as a day case. This study evaluates the suitability of TEP repair in the day-care setting. METHODS: A policy of day-care TEP repair, unless contraindicated, was adopted for inguinal hernia repair, and the outcome was prospectively evaluated. Of 87 consecutive inguinal hernia repairs, day-care TEP was possible in 54 (62%); 17 (20%) were in-patient TEP, 14 (16%) were open repairs, and 2 (2%) were converted from TEP to open repairs. RESULTS: Among day-care TEP repairs, median visual analog pain score at discharge was 2.3/10, and 43% of patients had no pain. Complications included cord hematoma 2 (4%) and seroma 3 (6%). Median times for stopping analgesia, resumption of full activity, and return to work were 3, 3, and 6 days respectively. Complete satisfaction with day-care TEP was expressed by 91% of patients; 9% were moderately satisfied, and none expressed dissatisfaction. CONCLUSIONS: Day-care TEP repair is feasible in the majority of patients with inguinal hernias, and it is associated with minimal complications, excellent recovery, and a high degree of patient satisfaction.

A randomized controlled trial of extraperitoneal bupivacaine analgesia in laparoscopic hernia repair.

BACKGROUND: The limited space developed in totally extraperitoneal laparoscopic inguinal hernia repair (TEP) provides the ideal setting for direct instillation of local anesthetic. This study evaluates the efficacy of extraperitoneal bupivacaine analgesia in patients undergoing day-care TEP. METHODS: Fifty-six consecutive patients were randomized to intraoperative extraperitoneal instillation of bupivacaine (n = 29) or normal saline control (n = 27). Patients were blindly assessed on discharge from hospital, at 24 hours, 1 week, and 1 month postoperatively. RESULTS: Compared with controls, patients treated with bupivacaine had lower median (range) visual analogue pain scores on discharge (1.5 [0 to 5.9] versus 3.7 [0.2 to 6.9], P = 0.03), and were more frequently pain free (54% versus 31%, P = 0.078). Although this difference had gone by 24 hours, the bupivacaine group continued to recover faster; stopping analgesia earlier (2 [0 to 7] days versus 3 [0 to 21] days, P = 0.01) and returning to full activity earlier (2.5 [1 to 14] days versus 5 [1 to 21] days, P = 0.013). Of bupivacaine patients 100% were completely satisfied with the procedure compared with 81% of controls (P = 0.02). CONCLUSION: Extraperitoneal bupivacaine minimizes pain following day-care TEP repair, facilitates recovery, and increases patient satisfaction. Benefits persist beyond the pharmacological action of bupivacaine.