Clinical characteristics and treatment patterns of patients with NTRK fusion-positive solid tumors: A multisite cohort study at US academic cancer centers.

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare oncogenic drivers prevalent in 0.3% of solid tumors. They are most common in salivary gland cancer (2.6%), thyroid cancer (1.6%), and soft-tissue sarcoma (1.5%). Currently, there are 2 US Food and Drug Administration-approved targeted therapies for NTRK gene fusions: larotrectinib, approved in 2018, and entrectinib, approved in 2019. To date, the real-world uptake of tyrosine receptor kinase inhibitor (TRKi) use for NTRK-positive solid tumors in academic cancer centers remains largely unknown. OBJECTIVE: To describe the demographics, clinical and genomic characteristics, and testing and treatment patterns of patients with NTRK-positive solid tumors treated at US academic cancer centers. METHODS: This was a retrospective chart review study conducted in academic cancer centers in the United States. All patients diagnosed with an NTRK fusion-positive (NTRK1, NTRK2, NTRK3) solid tumor (any stage) and who received cancer treatment at participating sites between January 1, 2012, and July 1, 2023, were included in this study. Patient demographics, clinical characteristics, genomic characteristics, NTRK testing data, and treatment patterns were collected from electronic medical records and analyzed using descriptive statistics as appropriate. RESULTS: In total, 6 centers contributed data for 55 patients with NTRK-positive tumors. The mean age was 49.3 (SD = 20.5) years, 51% patients were female, and the majority were White (78%). The median duration of time from cancer diagnosis to NTRK testing was 85 days (IQR = 44-978). At the time of NTRK testing, 64% of patients had stage IV disease, compared with 33% at cancer diagnosis. Prevalent cancer types in the overall cohort included head and neck (15%), thyroid (15%), brain (13%), lung (13%), and colorectal (11%). NTRK1 fusions were most common (45%), followed by NTRK3 (40%) and NTRK2 (15%). Across all lines of therapy, 51% of patients (n = 28) received a TRKi. Among TRKi-treated patients, 71% had stage IV disease at TRKi initiation. The median time from positive NTRK test to initiation of TRKi was 48 days (IQR = 9-207). TRKis were commonly given as first-line (30%) or second-line (48%) therapies. Median duration of therapy was 610 (IQR = 182-764) days for TRKi use and 207.5 (IQR = 42-539) days for all other first-line therapies. CONCLUSIONS: This study reports on contemporary real-world NTRK testing patterns and use of TRKis in solid tumors, including time between NTRK testing and initiation of TRKi therapy and duration of TRKi therapy.

Oxidative damage in the gastrocnemius predicts long-term survival in patients with peripheral artery disease.

Patients with peripheral artery disease (PAD) have increased mortality rates and a myopathy in their affected legs which is characterized by increased oxidative damage, reduced antioxidant enzymatic activity and defective mitochondrial bioenergetics. This study evaluated the hypothesis that increased levels of oxidative damage in gastrocnemius biopsies from patients with PAD predict long-term mortality rates. Oxidative damage was quantified as carbonyl adducts in myofibers of the gastrocnemius of PAD patients. The oxidative stress data were grouped into tertiles and the 5-year, all-cause mortality for each tertile was determined by Kaplan-Meier curves and compared by the Modified Peto test. A Cox-regression model was used to control the effects of clinical characteristics. Results were adjusted for age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidities. Of the 240 study participants, 99 died during a mean follow up of 37.8 months. Patients in the highest tertile of oxidative damage demonstrated the highest 5-year mortality rate. The mortality hazard ratios (HR) from the Cox analysis were statistically significant for oxidative damage (lowest vs middle tertile; HR = 6.33; p = 0.0001 and lowest vs highest; HR = 8.37; p < 0.0001). Survival analysis of a contemporaneous population of PAD patients identifies abundance of carbonyl adducts in myofibers of their gastrocnemius as a predictor of mortality rate independently of ankle-brachial index, disease stage and other clinical and myopathy-related covariates.

Prolonged Cancer Control With Adagrasib in Patients With Metastatic, KRASG12C-Mutated NSCLC After Sotorasib-Induced Hepatotoxicity: A Case Report.

Both sotorasib and adagrasib are approved for use in metastatic KRASG12C-mutated NSCLC after cancer progression on chemotherapy and immunotherapy. Hepatoxicity is a commonly encountered adverse effect of both agents, and little data exists about the safety of sequential use of these agents when hepatotoxicity is encountered. In this case report, we describe a patient who developed recurrent hepatotoxicity with sotorasib and was able to switch to adagrasib without hepatotoxicity and subsequently experienced a prolonged cancer response. We also describe a previously unreported adagrasib adverse effect of photoinduced skin hyperpigmentation.

Multicenter Phase 1b/2a Clinical Trial of Radioprotectant BIO 300 Oral Suspension for Patients With Non-Small Cell Lung Cancer Receiving Concurrent Chemoradiotherapy.

PURPOSE: Radiation therapy is part of the standard treatment regimen for non-small cell lung cancer (NSCLC). Although radiation therapy is an effective tool to manage NSCLC, it can be associated with significant dose-limiting toxicities. These toxicities can lead to treatment interruption or early termination and worsening clinical outcomes in addition to reductions in patient quality of life. Based on preclinical efficacy for radioprotection of normal tissues, we evaluated the clinical utility of BIO 300 Oral Suspension (BIO 300; synthetic genistein nanosuspension) in patients with NSCLC. METHODS AND MATERIALS: In this multicenter, open-label, single-arm, ascending dose phase 1b/2a study, patients were enrolled with newly diagnosed stage II-IV NSCLC planned for 60 to 70/1.8-2.0 Gy radiation therapy and concurrent weekly paclitaxel/carboplatin. Oral BIO 300 (cohort 1, 500 mg/d; cohort 2, 1000 mg/d; cohort 3, 1500 mg/d) was self-administered once daily starting 2 to 7 days before initiating concurrent chemoradiotherapy and continued until the end of radiation therapy. The primary endpoint was acute dose-limiting toxicities attributable to BIO 300. Secondary outcomes included pharmacokinetics, pharmacodynamics, overall toxicity profile, quality of life, local response rate, and survival. RESULTS: Twenty-one participants were enrolled. No dose-limiting toxicities were reported. BIO 300 dosing did not alter chemotherapy pharmacokinetics. Adverse events were not dose-dependent, and those attributable to BIO 300 (n = 11) were all mild to moderate in severity (grade 1, n = 9; grade 2, n = 2) and predominantly gastrointestinal (n = 7). A dose-dependent decrease in serum transforming growth factor ß1 levels was observed across cohorts. Based on safety analysis, the maximum tolerated dose of BIO 300 was not met. Patient-reported quality of life and weight were largely stable throughout the study period. No patient had progression as their best overall response, and a 65% tumor response rate was achieved (20% complete response rate). CONCLUSIONS: The low toxicity rates, along with the pharmacodynamic results and tumor response rates, support further investigation of BIO 300 as an effective radioprotector.

Metabolic and Bariatric Surgery Utilization Trends in the United States: Evidence From 2012 to 2021 National Electronic Medical Records Network.

Background: Bariatric surgery has evolved over the past 2 decades yet assessing trends of bariatric surgery utilization in the growing eligible population is lacking. Aim: This study aimed to update the trends in bariatric surgery utilization, changes in types of procedures performed, and the characteristics of patients who underwent bariatric surgery in the United States, using real-world data. Method: This retrospective descriptive observational study was conducted using the TriNetX, a federated electronic medical records network from 2012 to 2021, for adult patients 18 years old or older who had bariatric surgery. Descriptive statistical analysis was conducted to assess patients' demographics and characteristics. Annual secular trend analyses were conducted for the annual rate of bariatric surgery, and the specific procedural types and proportions of laparoscopic surgeries. Results: A steady increase in the number of procedures performed in the United States over the first 6 years of the study, a plateau for the following 2 years, and then a decline in 2020 and 2021 (during the coronavirus disease 2019 pandemic). The annual rate of bariatric surgery was lowest in 2012 at 59.2 and highest in 2018 at 79.6 surgeries per 100,000 adults. During the study period, 96.2% to 98.8% of procedures performed annually were conducted laparoscopically as opposed to the open technique. Beginning in 2012, the Roux-en-Y gastric bypass (RYGB) procedure fell to represent only 17.1% of cases in 2018, along with a sharp decline in the adjustable gastric band (AGB) procedure, replaced by a sharp increase in the sleeve gastrectomy (SG) procedure to represent over 74% of cases in 2018. Conclusions: Bariatric surgery utilization in the United States showed a moderate decline in the number of RYGB procedures, which was offset by a substantial increase in the number of SG procedures and a precipitous drop in the annual number of AGB procedures.

Arthroscopic Treatment of the Septic Ankle.

Ankle joint sepsis is a relatively rare but potentially devastating pathologic process of the lower extremity that requires expeditious identification and management. Establishing the diagnosis of ankle joint sepsis is often challenging as it may present with concomitant pathologies and often lacks consistency in regard to classic clinical characteristics. Once a diagnosis has been established, prompt management is imperative to minimize the potential for long-term sequelae. The purpose of this chapter is to address the diagnosis and management of the septic ankle with a focus on arthroscopic treatment.

Resected cytokeratin-negative small cell lung carcinoma.

Small cell lung carcinoma (SCLC), a malignancy of neuroendocrine origin, can show varied morphologies and patterns but is typically positive for at least one neuroendocrine marker and almost always for cytokeratins. It is essential to distinguish this tumour due to its characteristic genetic features, aggressive behaviour, propensity for metastasis and responsiveness to chemotherapy. We hereby present a rare case of a pulmonary mass that showed morphological features of an SCLC but lacked cytokeratin expression on biopsy as well as resection specimens. Various cytokeratins were tested on multiple blocks and at different laboratories. A broad differential diagnosis was considered and ruled out including small round blue cell tumours, non-SCLC and metastasis. After performing an extensive work-up to identify the origin of this tumour, it was finally diagnosed as SCLC with expression of neuroendocrine markers synaptophysin and CD56, and intracytoplasmic electron dense neurosecretory granules (250-350 nm) however lacked cytokeratin expression.

In vitro sepsis up-regulates Nociceptin/Orphanin FQ receptor expression and function on human T- but not B-cells.

BACKGROUND AND PURPOSE: In animal models of sepsis, increased activation of the Nociceptin/Orphanin FQ (N/OFQ) receptor NOP is associated with mortality and NOP antagonists improved survival. We have explored the role of the N/OFQ-NOP system in freshly isolated volunteer human B- and T-cells incubated with lipopolysaccharide (LPS) and peptidoglycan G (PepG) as a model of in vitro sepsis. EXPERIMENTAL APPROACH: B- and T-cell NOP expression was measured using the NOP fluorescent probe N/OFQATTO594 , N/OFQ content was measured using immunofluorescence, N/OFQ release was tracked using a CHOhNOPGαiq5 biosensor assay and NOP function was measured using transwell migration and cytokine/chemokine release using a 25-plex assay format. Cells were challenged with LPS/PepG. KEY RESULTS: CD19-positive B-cells bound N/OFQATTO594 ; they also contain N/OFQ. Stimulation with CXCL13/IL-4 increased N/OFQ release. N/OFQ trended to reduced migration to CXCL13/IL-4. Surface NOP expression was unaffected by LPS/PepG, but this treatment increased GM-CSF release in an N/OFQ sensitive manner. CD3-positive T-cells did not bind N/OFQATTO594 ; they did contain N/OFQ. Stimulation with CXCL12/IL-6 increased N/OFQ release. When incubated with LPS/PepG, NOP surface expression was induced leading to N/OFQATTO594 binding. In LPS/PepG-treated cells, N/OFQ reduced migration to CXCL12/IL-6. LPS/PepG increased GM-CSF release in an N/OFQ sensitive manner. CONCLUSIONS AND IMPLICATIONS: We suggest both a constitutive and sepsis-inducible N/OFQ-NOP receptor autocrine regulation of B- and T-cell function, respectively. These NOP receptors variably inhibit migration and reduce GM-CSF release. These data provide mechanistic insights to the detrimental role for increased N/OFQ signalling in sepsis and suggest a potential role for NOP antagonists as treatments.

Comprehensive genomic profiling: Does timing matter?

Purpose: There is variability in utilization of Comprehensive Genomic Profiling (CGP) in most of the metastatic solid tumors (MST). We evaluated the CGP utilization patterns and its impact on outcomes at an academic tertiary center. Patients and Methods: Institutional database was reviewed for CGP data in adult patients with MST between 01/2012 - 04/2020. Patients were categorized based on interval between CGP and metastatic diagnosis; 3 tertiles of distribution (T1-earliest to the diagnosis, T3-furthest), and pre-mets (CGP performed prior to diagnosis of metastasis). Overall survival (OS) was estimated from the time of metastatic diagnosis with left truncation at the time of CGP. Cox regression model was used to estimate the impact of timing of CGP on survival. Results: Among 1,358 patients, 710 were female, 1,109 Caucasian, 186 Afro-Americans, and 36 Hispanic. The common histologies were lung cancer (254; 19%), colorectal cancer (203; 15%), gynecologic cancers (121; 8.9%), and pancreatic cancer (106; 7.8%). Time interval between diagnosis of metastatic disease and CGP was not statistically significantly different based on sex, race and ethnicity after adjusting for histologic diagnoses with 2 exceptions - Hispanics with lung cancer had delayed CGP compared to non-Hispanics (p =0.019) and females with pancreas cancer had delayed CGP compared to males (p =0.025). Lung cancer, gastro-esophageal cancer and gynecologic malignancies had better survival if they had CGP performed during the first tertile after metastatic diagnosis. Conclusion: CGP utilization across cancer types was equitable irrespective of sex, race and ethnicity. Early CGP after metastatic diagnosis might have effect on treatment delivery and clinical outcomes in cancer type with more actionable targets.

Evaluation of outpatient treatment for non-hospitalised patients with COVID-19: The experience of a regional centre in the UK.

INTRODUCTION: Antivirals, such as molnupiravir, and SARS-CoV-2 neutralising monoclonal antibodies (nMAbs), such as sotrovimab, reduced the risk of hospitalisation and death in clinical trials of high-risk non-hospitalised patients with Covid-19. However, the real-world benefits of these drugs are unclear. AIMS: To evaluate the characteristics and outcomes of high-risk patients referred for outpatient antiviral or nMAb treatment for symptomatic Covid-19. METHODS: The records of patients referred to a large UK Covid Medicines Delivery Unit (CMDU) over nine weeks (December 2021-February 2022) were reviewed. Data were collected on demographics, referral indications, vaccination, deprivation, treatment, complications, hospital admission, and mortality. RESULTS: 1820 patients were referred to the CMDU, with 604 (33.2%) suitable for further assessment. 169 patients received sotrovimab, 80 patients received molnupiravir, 70 patients declined treatment, and 266 were ineligible for treatment because of resolving symptoms. There were trends towards higher proportions of female and white patients, lower deprivation scores, and malignancy- or transplant-related indications in the groups receiving treatment compared with untreated patients. Covid-19-related hospitalisations occurred in 1.2% of the treated group and 3.0% of the untreated group indicating a potential treatment effect, however Covid-related hospitalisations were lower than reported in the original clinical trials (2.2% compared with 7-10%). CONCLUSION: The referral pathways for outpatient treatment of Covid-19 are inefficient, and the UK system may not be serving all groups equitably. Hospitalisation with Covid-19 was rare regardless of treatment. Ongoing service evaluation is required to ensure efficient use of resources for the outpatient management of Covid-19.

Effect of a continuous perineural levobupivacaine infusion on pain after major lower limb amputation: a randomised double-blind placebo-controlled trial.

OBJECTIVES: Randomised controlled trial of the effect of a perineural infusion of levobupivacaine on moderate/severe phantom limb pain 6 months after major lower limb amputation. SETTING: Single-centre, UK university hospital. PARTICIPANTS: Ninety patients undergoing above-knee and below-knee amputation for chronic limb threatening ischaemia under general anaesthesia. Exclusion criteria were patients having surgery under neuraxial anaesthesia; inability to operate a patient-controlled analgesia device or complete a Visual Analogue Scale; amputation for trauma or malignancy; or contraindication to levobupivacaine. INTERVENTIONS: Either levobupivacaine 0.125% or saline 0.9% (10 mL bolus, infusion of 8 mL/hour for 96 hours) via a sciatic or posterior tibial nerve sheath catheter placed under direct vision during surgery. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the presence of phantom limb pain, residual limb pain and phantom limb sensations up to 6 months after amputation. Secondary outcome measures included early postoperative pain and morphine requirements after surgery. RESULTS: Data from 81 participants were analysed; 6-month follow-up data were available for 62 patients. Pain and morphine requirements varied widely before and after amputation in both groups. The incidences of moderate/severe phantom limb pain, residual limb pain and phantom limb sensations were low from 6 weeks with no significant differences between groups in phantom limb pain at rest (OR 0.56, 95% CI 0.14 to 2.14, p=0.394) or movement (OR 0.58, 95% CI 0.15 to 2.21, p=0.425) at 6 months. Early postoperative pain scores were low in both groups with no between-group differences in residual limb pain or phantom limb sensations (rest or movement) at any time point. High postoperative morphine consumption was associated with worsening phantom limb pain both at rest (-17.51, 95% CI -24.29 to -10.74; p<0.001) and on movement (-18.54, 95% CI -25.58 to -11.49; p<0.001). The incidence of adverse effects related to the study was low in both groups: postoperative nausea, vomiting and sedation scores were similar, and there were no features of local anaesthetic toxicity. CONCLUSIONS: Long-term phantom limb pain, residual limb pain and phantom limb sensations were not reduced significantly by perineural infusion of levobupivacaine, although the study was underpowered to show significant differences in the primary outcome. The incidence of phantom limb pain was lower than previously reported, possibly attributable to frequent assessment and early intervention to identify and treat postoperative pain when it occurred. There were large variations in postoperative pain scores, high requirements for analgesics before and after surgery and some problems maintaining recruitment and long -term follow-up. Knowledge of these potential problems should inform future research in this group of patients. Further work should investigate the association between perioperative morphine requirements and late phantom limb pain. TRIAL REGISTRATION NUMBERS: EudraCT 2007-000619-27; ISRCTN68691928.

Differences between two sequential uncemented stem sizes in total hip arthroplasty: A comparative biomechanical study and potential clinical implications.

BACKGROUND: Early failure of uncemented femoral stems associated with incorrect sizing is a known postoperative complication. Surgeons are often faced with the question of whether an uncemented stem of adequate stability or a larger-sized stem should be implanted, especially when the proximal femoral cancellous bone is adequate. The biomechanical effect of sub-optimal stem sizing in the femur remains unclear. This study investigated the mechanical behaviour of two sequential sized uncemented stems of the same type. METHODS: Six laboratory models of synthetic non-osteoporotic femora were randomly divided into two groups and implanted with either a nominal or oversized uncemented hydroxyapatite-coated nonporous titanium collarless stem. Stiffness, uniaxial strain, and pattern of strain distribution were measured under an anatomical one-legged stance. RESULTS: Oversized stems demonstrated a higher overall stiffness compared to nominal; however, this was not statistically significant. The nominal stem showed a higher strain in the neck and the proximal medial diaphyseal region. The oversized stem showed higher strains in the distal region around the implant tip. CONCLUSION: Opting to use a larger stem may potentially increase primary stability, thus allowing safer early mobility. However, higher stiffness may lead to stress shielding, bone loss, and thigh pain in the long term. In addition, strains in the diaphysis and the tip of the stem may predispose to periprosthetic fractures, especially in osteoporotic bones, making this a relatable aspect for users and biomechanical loading. Given the wide range of complex factors that need to be considered when choosing stem size in uncemented THA surgery, this study's results should be interpreted cautiously.

Isolation of Raoultella ornithinolytica in a HIV positive patient with a lung abscess.

A 38 year old male HIV positive patient with a history of intravenous drug use presented with chest pains, cough, sputum and weight loss and radiology demonstrated the evolution of a right basal lung abscess. A lung biopsy sent for 16S rRNA analysis and sputum cultured about the same time demonstrated Raoultella ornithinolytica . No other causative pathogens were clearly identified. He gradually improved with a 4 week course of intravenous cefazolin. R. ornithinolytica is a rare, but recognised pathogen.

Erroneous Central Venous Catheter Placement: Multidisciplinary Primary Surgical Repair of the Vertebral Artery.

Central venous catheters are a common practice in critical care medicine. These lines are of particular importance when a patient needs large volume resuscitation or medications that cannot be infused through a peripheral line. Even though central venous catheters are frequently utilized, they are associated with potentially significant risks that one must be aware of when attempting placement. The anatomy and pertinent complications are key for any healthcare professional to be aware of during this procedure. As such, vascular injury has been described in the literature, but vertebral artery injury and common repair techniques are less common. Primary repair of the second vertebral artery segment is infrequently detailed in the literature and this report describes pertinent case details and plan of action for identification and repair of iatrogenic vertebral artery injury following catheter placement.

85-Year-Old Postsurgical Complex Patient Successfully Managed Remotely at the Novel Mayo Clinic's Hospital at Home.

An 85-year-old male presented to the podiatry clinic following a 1st to 5th left toe amputation as a complication of severe peripheral arterial disease and nonhealing wound despite endovascular intervention with an angiogram. At the visit, cellulitis with gangrene of the surgical site was noted. The patient was admitted to the brick and mortar (BAM) hospital and taken to surgery for a transmetatarsal amputation of the left limb. In the immediate postoperative period, the incisional margins appeared dusky creating concern for flap viability. The medical team recommended a vascular bypass versus a below-knee amputation. However, given the age, comorbidities, and nutritional status, the family refused further surgical intervention. As such, Mayo Clinic's home hospital program, Advanced Care at Home (ACH), was consulted for continued nonsurgical acute management at home. The patient was transferred to ACH and transported home three days after BAM admission to continue IV antibiotic therapy and wound care. Discharge from ACH occurred 11 days after admission to the BAM hospital. This case highlights the importance of developing health care alternatives to traditional hospitalization and demonstrates that ACH can manage highly complex, elder postoperative patients from the comfort of their homes.

Multisite study of Titan SGS stapler in longitudinal gastric resection.

BACKGROUND: Standardization of the laparoscopic sleeve gastrectomy procedure is needed to improve patient outcomes. A single-fire 23 cm stapler was developed to streamline the operation. Comparative testing conducted on excised human tissue has demonstrated the superiority of the novel Titan SGS stapler to two commonly utilized commercial devices in both staple line integrity and burst pressure. We hypothesized that the stapler would be safe and effective in creating longitudinal gastric resections in human patients. METHODS: 61 patients were enrolled to undergo gastric resection with the Titan SGS stapler. Perioperative interventions and post-operative adverse events were recorded. Upper GI study was completed on post-operative day 1, and patients were followed for 6 weeks post-operatively to determine any subacute device-related adverse events. RESULTS: Surgeon feedback for intraoperative device utilization and post-operative gastric pouch shape were positive. Adverse events were found to be mild, limited, and generally well-known effects of bariatric surgery. One episode of post-operative hemorrhage required surgical takeback, with no criminal bleeding vessel identified. CONCLUSION: The Titan SGS stapler is both safe and effective in sleeve gastrectomy pouch creation.

Surprising neutral effect of shorter staple cartridges in laparoscopic sleeve gastrectomy.

BACKGROUND: Consensus agreements regarding laparoscopic sleeve gastrectomy (LSG) advise against using staple loads less than 1.5 mm in closed staple height. However, few data exist to support this recommendation. We hypothesized that using staples with a shorter closed height would actually decrease incidence of intraoperative and postoperative bleeding during LSG, while not increasing the incidence of leak. METHODS: All LSG cases for a single institution from 1/1/2014 to 12/31/2019 were exported for analysis. Two cohorts were established: 1. 'Green/Blue' group was cases in which no white cartridges were used and 2. 'White' group was cases in which any white cartridges were used. Demographic variables, procedural characteristics, hospital length of stay, and postoperative outcomes were compared between groups. RESULTS: The study populations included 1710 patients, 974 in the green/blue group and 736 in the white cartridge group. There were no significant differences in postoperative leak, bleed, stricture, readmission, or death while using white staple loads as compared with the standard combination of blue and green loads. CONCLUSION: Using staples with a shorter closed height during LSG did not impact the postoperative bleeding or leak rate. The impact from selection of shorter staples to achieve more tissue compression may be limited.

Constructing operating theatre schedules using partitioned graph colouring techniques.

In hospitals, scheduled operations can often be cancelled in large numbers due to the unavailability of beds for post-operation recovery. Operating theatre scheduling is known to be an N P -hard optimisation problem. Previous studies have shown that the correct scheduling of surgical procedures can have a positive impact on the availability of beds in hospital wards, thereby allowing a reduction in number of elective operation cancellations. This study proposes an exact technique based on the partitioned graph colouring problem for constructing optimal master surgery schedules, with the goal of minimising the number of cancellations. The resultant schedules are then simulated in order to measure how well they cope with the stochastic nature of patient arrivals. Our results show that the utilisation of post-operative beds can be increased, whilst the number of cancellations can be decreased, which may ultimately lead to greater patient throughput and reduced waiting times. A scenario-based model has also been employed to integrate the stochastic-nature associated with the bed requirements into the optimisation process. The results indicate that the proposed model can lead to more robust solutions.

Endocutter Staple Height Auto-Adjusts to Tissue Thickness.

BACKGROUND: Surgeon choice of the appropriate staple height has been cited as a factor in the mechanical integrity of a staple line. However, tissue measured at the industry standard 8 g/mm2 is usually thicker than the formed staple height of the staples that hold it together. This means that the pressure that the staples apply must be greater than 8g/mm2. Additionally, formed staple heights in tissue may be different than formed staple heights of the same cartridge type when fired without tissue. This means that there is likely a compressive limit to the individual staples deployed by the stapling system. The purpose of this study is to establish the degree to which staple heights of endocutter staples auto-adjust to tissue and the compressive limit to tissue that this infers. MATERIALS AND METHODS: Excised gastric remnants from laparoscopic sleeve gastrectomy were measured for tissue thickness at different external pressures. An optimized experimental staple line was then created in parallel to the clinical staple line. The doubly-stapled gastric sliver then underwent computed tomography with solid modeling software to measure staple heights. RESULTS: Staple heights fired in gastric tissue were significantly different than industry labelled and control staple heights. Clinical staple heights were significantly shorter than measured tissue thickness at 8 g/mm2. Staple height more closely approximated tissue thickness under 15 g/mm2 of pressure, rather than the 8 g/mm2 loading pressure used by industry for tissue thickness range labelling. CONCLUSIONS: Staples deployed in human gastric tissue are taller than commercial labelling. The closed staple height corresponds to tissue thickness under 15g/mm2 of pressure, not the labelled staple height. These results demonstrate that staple heights from modern endocutter staplers adjust to tissue, approximating a maximum compressive force just above 15g/mm2.