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Background Adhesive small bowel obstruction (aSBO) is a potentially recurrent disease. Although non‐operative management is often successful, it is associated with greater risk of recurrence than operative intervention, and may have greater downstream morbidity and costs. This study aimed to compare the current standard of care, trial of non‐operative management (TNOM), and early operative management (EOM) for aSBO. Methods Patients admitted to hospital between 2005 and 2014 in Ontario, Canada, with their first episode of aSBO were identified and propensity‐matched on their likelihood to receive EOM for a cost–utility analysis using population‐based administrative data. Patients were followed for 5 years to determine survival, recurrences, adverse events and inpatient costs to the healthcare system. Utility scores were attributed to aSBO‐related events. Cost–utility was presented as the incremental cost‐effectiveness ratio (ICER), expressed as Canadian dollars per quality‐adjusted life‐year (QALY). Results Some 25 150 patients were admitted for aSBO and 3174 (12·6 per cent) were managed by EOM. Patients managed by TNOM were more likely to experience recurrence of aSBO (20·9 per cent versus 13·2 per cent for EOM; P < 0·001). The lower recurrence rate associated with EOM contributed to an overall net effectiveness in terms of QALYs. The mean accumulated costs for patients managed with EOM exceeded those of TNOM ( $17 951 versus $ 11 594 (€12 288 versus €7936) respectively; P < 0·001), but the ICER for EOM versus TNOM was$29 881 (€20 454) per QALY, suggesting cost‐effectiveness. Conclusion This retrospective study, based on administrative data, documented that EOM may be a cost‐effective approach for patients with aSBO in terms of QALYs. Future guidelines on the management of aSBO may also consider the long‐term outcomes and costs. Antecedentes La oclusión de intestino delgado por adherencias (adhesive small bowel obstruction, aSBO) es una enfermedad potencialmente recidivante. Aunque el tratamiento no quirúrgico es a menudo eficaz, se asocia con un mayor riesgo de recidiva que la intervención quirúrgica, y puede provocar más adelante morbilidad y costes. El objetivo de este estudio fue comparar un Ensayo de Tratamiento No Quirúrgico (Trial of Non‐operative Management, TNOM, el estándar actual de tratamiento) con Tratamiento Operatorio Precoz (Early Operative Management, EOM) para el tratamiento de aSBO. Métodos Pacientes ingresados en el hospital entre 2005‐2014 en Ontario, Canadá con un primer episodio de aSBO fueron identificados y emparejados por puntaje de propensión respecto a la probabilidad de recibir EOM para un análisis de coste‐utilidad utilizando datos administrativos de base poblacional. Los pacientes fueron seguidos durante 5 años para determinar la supervivencia, recidivas, eventos adversos, y costes de la hospitalización para el sistema de salud. Las puntuaciones de utilidad se atribuyeron a los eventos relacionados con la aSBO. El coste‐utilidad se presentó como la razón costo efectividad incremental (incremental cost‐effectiveness ratio, ICER) expresada como dólares por año de vida ajustado por calidad (quality‐adjusted life‐year, QALY). Resultados Un total de 25.150 pacientes fueron ingresados por aSBO y 3.174 (12,6%) fueron tratados con EOM. Los pacientes tratados mediante TNOM tenían más probabilidades de presentar una recidiva de la aSBO (20,9% versus 13,2%, P < 0,0001). La menor incidencia de recidivas asociada con EOM contribuyó a una eficacia neta global en términos de QALYs. Mientras que los costes medios acumulados para los pacientes tratados con EOM superaron a los de TNOM ($ 17,951 versus$11,594, P < 0,0001), el ICER de EOM versus TNOM fue $ 29,881/QALY, lo que sugiere un coste‐eficacia de esta estrategia. Conclusión Este estudio retrospectivo basado en datos administrativos evidenció que EOM puede representar un abordaje coste‐efectivo para pacientes con aSBO en términos de QALYs. Las futuras guías clínicas para el tratamiento de la aSBO pueden también considerar los resultados a largo plazo y los costes. This population‐based cost–utility analysis compared early operative management (EOM) for adhesive small bowel obstruction (SBO) to the current standard of care of a trial of non‐operative management. Although EOM was more costly, it was associated with a significantly lower risk of recurrence and reduced exposure to the morbidity and costs associated with multiple admissions for adhesive SBO. With longer follow‐up, EOM becomes increasingly cost‐effective, and crosses published willingness‐to‐pay thresholds within 5 years of the first admission. Early operative management in small bowel occlusion

Background Post-operative pain management is a critical component of perioperative care. Patients at risk of poorly controlled post-operative pain may benefit from early measures to optimize pain management. We sought to identify risk factors for post-operative pain and opioid consumption in patients undergoing liver resection. Methods This is a multi-institutional prospective nested cohort study of patients undergoing open liver resection. Opioid consumption and pain scores were collected following surgery. To estimate the effects of patient factors on opioid consumption (oral morphine equivalents—OME) and on pain scores (NRS-11), we used generalized linear models and multivariable linear regression model, respectively. Results One hundred and fifty-three patients who underwent open liver resection between 2013 and 2016 were included in the study. The mean patient age was 62.2 years, and 43.3% were female. Younger patients were significantly more likely to use more opioids in the early post-operative period (16.7 OME/10 years, p  < 0.001). Patient factors that were significantly associated with increased NRS-11 pain scores also included younger patient age (difference in pain score of 0.3/10 years with cough and 0.2/10 years at rest, p  < 0.01 for both) as well as a history of analgesic use (difference in pain score of 0.9 with cough and 0.6 at rest, p  < 0.01 and p  = 0.07, respectively). Conclusion Younger patients and those with a history of analgesic use are more likely to report higher post-operative pain and require higher doses of opioids. Early identification of these patients, and measures to better manage their pain, may contribute to optimal perioperative care.

IntroductionSurgical stress results in immune dysfunction, predisposing patients to infections in the postoperative period and potentially increasing the risk of cancer recurrence. Perioperative immunonutrition with arginine-enhanced diets has been found to potentially improve short-term and cancer outcomes. This study seeks to measure the impact of perioperative immunomodulation on biomarkers of the immune response and perioperative outcomes following hepatopancreaticobiliary surgery.Methods and analysisThis is a 1:1:1 randomised, controlled and blinded superiority trial of 45 patients. Baseline and perioperative variables were collected to evaluate immune function, clinical outcomes and feasibility outcomes. The primary outcome is a reduction in natural killer cell killing as measured on postoperative day 1 compared with baseline between the control and experimental cohorts.Ethics and disseminationThis trial has been approved by the research ethics boards at participating sites and Health Canada (parent control number: 223646). Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov (identifier: NCT04549662). Any modifications to the protocol will be communicated via publications and ClinicalTrials.gov.Trial registration numberClinicalTrials.gov identifier: NCT04549662.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammatory condition affecting nasal passages and sinus cavities, often leading to symptoms such as nasal congestion, decreased sense of smell, nasal discharge, and facial pain. When medical management fails, functional endoscopic sinus surgery (FESS) is employed. However, surgical visibility and blood loss during the procedure can significantly impact outcomes. Patients and methods A double-blind, controlled randomized trial was conducted on 50 patients suffering from CRSwNP, who were randomly divided into two groups. Group A received 30 mg of prednisolone orally 5 days before surgery, while group B received the same dosage 10 days before surgery. Surgical visibility was assessed using the Boezaart visibility score, and total operative blood loss and operative time were recorded. Results Group A exhibited a slightly higher surgical visibility score (1.93 ± 0.35) compared to group B (1.85 ± 0.23), although this difference was not statistically significant ( P  = 0.38). Conversely, group A had significantly higher total operative blood loss (172 ± 43.49 ml) compared to group B (145 ± 30 ml), with a significant P -value of 0.02. Operative times were nearly identical, averaging 146 ± 38.25 min for group A and 145.8 ± 37.59 min for group B, showing no significant difference ( P  = 0.99). Conclusion There was no significant difference in surgical field visibility or operative time in patients receiving preoperative 30 mg/day of oral prednisone for 5 days compared to 10 days prior to endoscopic sinus surgery for sinonasal polyps. There was a statistically significant improvement in total operative blood loss; yet, the authors do not consider it clinically significant. Therefore, the authors would recommend the shorter 5-day course rather than the longer 10-day course.

Background Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Adjuvant imatinib therapy improves recurrence-free and overall survival following surgery for patients with high-risk GIST; however, the factors associated with use of adjuvant imatinib therapy are unclear, and adherence to adjuvant imatinib has not been investigated. We sought to determine the clinicopathologic predictors of therapy with adjuvant imatinib following surgical resection for GIST and to determine the utilization of adjuvant imatinib in patients who underwent surgical resection of primary GIST in 2009 or later as recommended by National Comprehensive Cancer network (NCCN) guidelines. Methods A multi-institutional cohort including 171 patients who underwent surgery for primary GIST at seven high-volume cancer centers in the USA and Canada between January 2009–December 2012 was used in this study. Receipt of adjuvant imatinib therapy was ascertained, and factors associated with imatinib therapy were analyzed. Results Following surgery for primary GIST, tumor size (<5.0 cm: ref; 5.0–9.9 cm: odds ratio (OR) 2.36, 95 % confidence interval (CI) 0.74–7.55; >10.0 cm: OR 9.15, 95 % CI 2.28–36.75; p  = 0.007), mitotic rate (≤5/50 mitoses per 50 high powered field [HPF]: ref; 6–10/50 HPF: OR 24.91, 95 % CI 3.64–170.35; >10/50 HPF: OR 5.80, 95 % CI 3.64–170.35; p  < 0.001), and neoadjuvant therapy (OR 9.52; 95 % CI 2.51–36.14; p  = 0.001) were associated with receipt of adjuvant imatinib therapy. Overall, 75 % of patients received appropriate treatment, 23 % of patients were undertreated, and 2 % of patients were overtreated as compared to NCCN guidelines. Adjuvant imatinib therapy was administered in only 53 % of patients for which the NCCN guidelines recommended adjuvant therapy. Conclusion The clinicopathologic factors associated with use of adjuvant imatinib therapy in patients following resection of primary GIST are consistent with established risk factors for recurrence. Adjuvant imatinib therapy remains underutilized in patients with intermediate and high-risk GIST and in patients who receive neoadjuvant therapy. Barriers to adjuvant imatinib therapy in this group of patients needs to be further explored.

Brightfield microscopy is the preferred method of pathologists for diagnosing solid tumors, utilizing common staining techniques such as hematoxylin and eosin staining and immunohistochemistry (IHC). However, as our understanding of the complex tumor microenvironment grows, there is increasing demand for multiplexed biomarker detection. Currently, multiplexed IHC assays are almost exclusively based on immunofluorescence because brightfield techniques are limited by the broad spectral absorption of chromogens and a reliance on conventional 3-channel color cameras. In this work, we overcome these limitations by combining new chromogens possessing narrow absorbance bands with matched illumination channels and monochrome imaging. Multiplex IHC was performed using four or five covalently deposited chromogens and hematoxylin nuclear stain to preserve morphological context and detail. Brightfield illumination was provided with a tungsten lamp/filter wheel combination or filtered light emitting diodes to provide up to 12 illumination wavelengths. In addition, an automated rapid imaging system was developed, using a synchronized 12-LED illuminator, that could capture images at all wavelengths in under 1 s. In one example, a four-biomarker multiplex assay was designed and used to distinguish regions of adenocarcinoma and squamous cell carcinoma in non-small cell lung cancer. The technology was also validated with a five-biomarker assay in prostate cancer. Spectrally unmixed images of each biomarker demonstrated concordant expression patterns with DAB single stain on serial sections, indicating faithful identification of each biomarker. In each assay, all chromogens were well resolved by spectral unmixing to remove spectral crosstalk. While further characterization and refinement of the assay, and improvements in automation and user interface are necessary for pathologist acceptance, this approach to multiplex IHC and multispectral imaging has the potential to accelerate adoption of multiplexing by combining the medical value of high-order multiplexing with the speed, pathologist familiarity, and broadly established clinical utility of brightfield microscopy. Brightfield multiplex immunohistochemistry (IHC) is improved by replacing broadly absorbing chromogens with narrowband covalently deposited chromogens, and sequentially illuminating with light channels matched to chromogen absorbance bands, synchronized with monochromatic image acquisition. Light emitting diodes provide a path to rapid multispectral imaging. Spectral unmixing provided accurate representations of biomarkers that faithfully reproduced 3,3′-diaminobenzidine IHC.

Multiplexed analysis of multiple biomarkers in a tissue sample requires use of reporter dyes with specific spectral properties that enable discrimination of signals. Conventional chromogens with broad absorbance spectra, widely used in immunohistochemistry (IHC), offer limited utility for multiplexed detection. Many dyes with narrow absorbance spectra, eg rhodamines, fluoresceins, and cyanines, potentially useful for multiplexed detection are well-characterized; however, generation of a chromogenic reagent useful for IHC analysis has not been demonstrated. Studies reported herein demonstrate utility of tyramine-chemistry for synthesis of a wide variety of new chromogenic dye conjugates useful for multiplexed in situ analysis using conventional light microscopes. The dyes, useful individually or in blends to generate new colors, provide signal sensitivity and dynamic range similar to conventional DAB chromogen, while enabling analysis of co-localized biomarkers. It is anticipated that this new paradigm will enable generation of a wide variety of new chromogens, useful for both research and clinical biomarker analysis that will benefit clinicians and patients.

Disclosure: S.R. Jafarian-Kerman: None. A. Razzeto: None. G. Saini: None. M. Siddiqui: None. M. Islam: None. D. Behman: None. M. Carson: None. Background: Recognizing Autoimmune Polyglandular Syndrome (AIPS) in a patient who has chronic hypothyroidism, specifically with a non-classic presentation, is challenging. Clinical Case: A woman in her 50’s with hypothyroidism presented with one week of progressive dizziness and weakness. Medications include levothyroxine 125 μg weekly (per the patient, her PCP started this dose 8 months ago based on lab results). On physical examination: BP 101/74 mmHg; HR 56 bpm; T: 98.1 F (36.7 C); RR: 23/min; O2 Sat: 98%. Skin: vitiligo. Lab results demonstrated TSH: 839.6 μIU/mL (0.5-4.5) from 0.28 one year ago, free T4: 0.15 ng/dL (0.4-4.5), phosphorus: 2.3 mg/dL (2.7-4.5), vitamin D: 17.4 ng/dL (>30). She was started on daily levothyroxine 125 μg and intravenous fluids. On day 3 of admission, Rapid Response was called for blood pressure 54/39 mmHg. Myxedema coma was unlikely as she lacked altered mental status, hypothermia, hypoventilation, hyponatremia, or hypoglycemia; CT head was normal. On the same day, hydrocortisone 100 mcg q8h started due to high suspicion of adrenal insufficiency given low normal cortisol [7.1 ug/dL (6-20)] and hypotension. Due to the history of hypothyroidism, vitiligo, and the new diagnosis of adrenal insufficiency, we suspected AIPS. two days later, primary adrenal insufficiency was established by a positive Cosyntropin stimulation test (1 hour cortisol of 14.8 ug/dL; not reaching >18 μg/dL), elevated ACTH 72 pg/mL (6-50), Aldosterone <1 ng/dL (3-16), and low DHEA of 52 ng/dL (345-2030). Other labs were as follow: normal FSH 85.7 mIU/mL (23-116), elevated PTH 153 pg/mL (16-77) which decreased to 62 pg/mL with vitamin D supplementation, normal Vitamin B12, and negative renin and intrinsic factor antibodies. A diagnosis of AIPS was established and she was discharged on levothyroxine, fludrocortisone, and hydrocortisone. Conclusion: AIPS is typically idiopathic and may affect endocrine organ systems either simultaneously or sequentially. The 3 classic patterns are: Type 1 (most common): younger women, presents with candidiasis, hypoparathyroidism, and Addison’s disease. Type 2: middle-aged women, Addison’s disease, autoimmune thyroid disease and/or Type 1 diabetes. Type 3: Type 1 diabetes, pernicious anemia, vitiligo or alopecia, and normal adrenal cortical function. This patient is unique in that she has characteristics of both type 1 and 3 AIPS, but not diabetes. In this case, the combination of hypotension even in the setting of profoundly undertreated hypothyroidism, prompted the expanded evaluation. While isolated hypothyroidism is common among our internal medicine patients, those with additional symptoms, or in this case unexplained hypotension, should be evaluated for AIPS. Presentation: Friday, June 16, 2023