Recurrent Peritonsillar Abscess Caused by Vaginal Flora: A Common Problem From a Unique Source.

Peritonsillar abscesses (PTAs) are typically caused by group A Streptococcus or mixed oral flora. Gardnerella vaginalis is a part of the normal vaginal microbiome, and overgrowth can cause bacterial vaginosis. We present a case of recurrent PTA with G. vaginalis superinfection, which occurred after the patient performed oral sex on a female after incision and drainage of her initial PTA. The patient continued to have recurrent PTAs until G. vaginalis was identified, and antibiotic coverage was broadened to cover both group A Streptococcus and G. vaginalis. This case highlights the importance of culturing PTA aspirate for directed antibiosis in persistent or recurrent infections. The rare superinfection also raises the question of advising abstinence from oral-genital contact after oral procedures to minimize risk of superinfection.

Consideration of factors associated with inequalities in interventions that support health-care professionals' interaction with patients to reduce inappropriate antimicrobial use: a systematic review.

BACKGROUND: Tackling the public health challenge of antimicrobial resistance (AMR) requires promotion of appropriate antimicrobial use by health-care professionals. The objective of this review was to identify interventions that facilitate appropriate antimicrobial behaviours when health-care professionals interact with patients and any considerations for factors associated with health inequalities. METHODS: For this systematic review, we searched electronic databases (MEDLINE, EMBASE, Web of Science and Google Scholar) from Jan 31, 2023, to Feb 8, 2023. We included search terms such as antimicrobial use/prescribing, health-care professionals, and AMR programmes. We included any relevant primary study published from year 2010 and in English. We conducted forward and backward citation searching from included studies on March 27, 2023. We extracted information on the interventions following the Template for Intervention Description and Replication (TIDieR) guideline and examined reports on how the interventions might impact on inequalities. We performed quality assessment using the Mixed Methods Appraisal Tool (MMAT). We conducted descriptive synthesis. The protocol is registered with PROSPERO (CRD42023395642). FINDINGS: After screening 4979 records, we included 59 studies. Most studies were randomised trials (n=25) and qualitative/mixed methods studies (n=16). Included studies covered 16 countries, particularly the UK (n=16) and the USA (n=13). Most studies (n=34) fulfilled at least 80% of the relevant quality criteria, but 12 studies fulfilled less than 50%. Many interventions were established strategies (eg, TARGET: Treat Antibiotics Responsibly, Guidance, Education and Tools). Patient interaction elements of the interventions often involved using education materials (eg, digital/paper leaflets, and videos) and point-of-care testing. While many studies (n=49) included participants from disadvantaged groups, only three examined how outcomes differ between groups. In those studies, antimicrobial prescription was not associated with age, sex, and level of learning disability. Some other studies reported issues with language barriers and potential digital exclusion, especially for older people. INTERPRETATION: We might have missed some relevant studies due to publication year and language restrictions. Notwithstanding, this review showed that the potential impact of factors associated with health inequalities are not routinely considered during the implementation and evaluation of interventions to improve health-care professionals' interaction with patients. Future work should routinely consider this to help mitigate potential inequalities. FUNDING: UK Health Security Agency.

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: A randomized controlled trial.

AIM: The aim was to determine whether specialist-led habit training using Habit Training with Biofeedback (HTBF) is more effective than specialist-led habit training alone (HT) for chronic constipation and whether outcomes of interventions are improved by stratification to HTBF or HT based on diagnosis (functional defaecation disorder vs. no functional defaecation disorder) by radio-physiological investigations (INVEST). METHOD: This was a parallel three-arm randomized single-blinded controlled trial, permitting two randomized comparisons: HTBF versus HT alone; INVEST- versus no-INVEST-guided intervention. The inclusion criteria were age 18-70 years; attending specialist hospitals in England; self-reported constipation for >6 months; refractory to basic treatment. The main exclusions were secondary constipation and previous experience of the trial interventions. The primary outcome was the mean change in Patient Assessment of Constipation Quality of Life score at 6 months on intention to treat. The secondary outcomes were validated disease-specific and psychological questionnaires and cost-effectiveness (based on EQ-5D-5L). RESULTS: In all, 182 patients were randomized 3:3:2 (target 384): HT n = 68; HTBF n = 68; INVEST-guided treatment n = 46. All interventions had similar reductions (improvement) in the primary outcome at 6 months (approximately -0.8 points of a 4-point scale) with no statistically significant difference between HT and HTBF (-0.03 points; 95% CI -0.33 to 0.27; P = 0.85) or INVEST versus no-INVEST (0.22; -0.11 to 0.55; P = 0.19). Secondary outcomes showed a benefit for all interventions with no evidence of greater cost-effectiveness of HTBF or INVEST compared with HT. CONCLUSION: The results of the study at 6 months were inconclusive. However, with the caveat of under-recruitment and further attrition at 6 months, a simple, cheaper approach to intervention may be as clinically effective and more cost-effective than more complex and invasive approaches.

Bacteriophage Therapy of Multidrug-resistant Achromobacter in an 11-Year-old Boy With Cystic Fibrosis Assessed by Metagenome Analysis.

BACKGROUND: Cystic fibrosis (CF) is a genetic disease associated with lung disease characterized by chronic pulmonary infection, increasingly caused by multiple drug-resistant pathogens after repeated antibiotic exposure, limiting antibiotic treatment options. Bacteriophages can provide a pathogen-specific bactericidal treatment used with antibiotics to improve microbiologic and clinical outcomes in CF. METHODS: Achromobacter species isolates from sputum of a chronically infected person with CF, were assessed for susceptibility to bacteriophages: 2 highly active, purified bacteriophages were administered intravenously every 8 hours, in conjunction with a 14-day piperacillin/tazobactam course for CF exacerbation. Sputum and blood were collected for metagenome analysis during treatment, with sputum analysis at 1-month follow-up. Assessments of clinical status, pulmonary status and laboratory evaluation for safety were conducted. RESULTS: Bacteriophage administration was well-tolerated, with no associated clinical or laboratory adverse events. Metagenome analysis documented an 86% decrease in the relative proportion of Achromobacter DNA sequence reads in sputum and a 92% decrease in blood, compared with other bacterial DNA reads, comparing pretreatment and posttreatment samples. Bacteriophage DNA reads were detected in sputum after intravenous administration during treatment, and at 1-month follow-up. Reversal of antibiotic resistance to multiple antibiotics occurred in some isolates during treatment. Stabilization of lung function was documented at 1-month follow-up. CONCLUSIONS: Bacteriophage/antibiotic treatment decreased the host pulmonary bacterial burden for Achromobacter assessed by metagenome analysis of sputum and blood, with ongoing bacteriophage replication documented in sputum at 1-month follow-up. Prospective controlled studies are needed to define the dose, route of administration and duration of bacteriophage therapy for both acute and chronic infection in CF.

Intercostal nerve cryoablation during surgical stabilization of rib fractures decreases post-operative opioid use, ventilation days, and intensive care days.

BACKGROUND: Intercostal nerve cryoablation is an adjunctive measure that has demonstrated pain control, decrease in opioid consumption, and decrease in hospital length of stay (LOS) in patients who undergo surgical stabilization of rib fractures (SSRF). METHODS: SSRF patients from January 2015 to September 2021 were retrospectively compared. All patients received multimodal pain regimens post-operatively and the independent variable was intraoperative cryoablation. RESULTS: 241 patients met inclusion criteria. 51 (21%) underwent intra-operative cryoablation during SSRF and 191 (79%) did not. Patients with standard treatment consumed 9.4 more daily MME (p = 0.035), consumed 73 percent more post-operative total MME (p = 0.001), spent 1.55 times as many days in the intensive care unit (p = 0.013), and spent 3.8 times as many days on the ventilator than patients treated with cryoablation, respectively. Overall hospital LOS, operative case time, pulmonary complications, MME at discharge, and numeric pain scores at discharge were no different (all p>0.05). CONCLUSION: Intercostal nerve cryoablation during SSRF is associated with fewer ventilator days, ICU LOS, total post-operative, and daily opioid use without increasing time in the operating room or perioperative pulmonary complications.

A Multicenter, Prospective Study Comparing Subxiphoid and Parasternal Views During Brief Echocardiography: Effect on Image Quality, Acquisition Time, and Visualized Anatomy.

BACKGROUND: Recent literature has suggested echocardiography (echo) may prolong pauses in chest compressions during cardiac arrest. OBJECTVES: We sought to determine the impact of the sonographic approach (subxiphoid [SX] vs. parasternal long [PSL]) on time to image completion, image quality, and visualization of cardiac anatomy during echo, as performed during Advanced Cardiac Life Support. METHODS: This was a multicenter, randomized controlled trial conducted at 29 emergency departments (EDs) assessing the time to image acquisition and image quality between SX and PSL views for echo. Patients were enrolled in the ED and imaged in a simulated cardiac arrest scenario. Clinicians experienced in echo performed both SX and PSL views, first view in random order. Image quality and time to image acquisition were recorded. Echos were evaluated for identification of cardiac landmarks. Data are presented as percentages or medians with interquartile ranges (IQRs). RESULTS: We obtained 6247 echo images, comprising 3124 SX views and 3123 PSL. Overall time to image acquisition was 9.0 s (IQR 6.7-14.1 s). Image acquisition was shorter using PSL (8.8 s, IQR 6.5-13.5 s) compared with SX (9.3 s, IQR 6.7-15.0 s). The image quality was better with the PSL view (3.86 vs. 3.54; p < 0.0001), twice as many SX images scoring in the worst quality category compared with PSL (8.6% vs. 3.7%). Imaging of the pericardium, cardiac chambers, and other anatomic landmarks was superior with PSL imaging. CONCLUSIONS: Echo was performed in < 10 s in > 50% of patients using either imaging technique. Imaging using PSL demonstrated improved image quality and improved identification of cardiac landmarks.

Laparoscopy is associated with decreased all-cause mortality in patients undergoing emergency general surgery procedures in a regional health system.

BACKGROUND: The aim of this study was to evaluate the use of laparoscopic surgery for common emergency general surgery (EGS) procedures within an integrated Acute Care Surgery (ACS) network. We hypothesized that laparoscopy would be associated with improved outcomes. METHODS: Our integrated health care system's EGS registry created from AAST EGS ICD-9 codes was queried from January 2013 to October 2015. Procedures were grouped as laparoscopic or open. Standard descriptive and univariate tests were performed, and a multivariable logistic regression controlling for open status, age, BMI, Charlson Comorbidity Index (CCI), trauma tier, and resuscitation diagnosis was performed. Laparoscopic procedures converted to open were identified and analyzed using concurrent procedure billing codes across episodes of care. RESULTS: Of 60,604 EGS patients identified over the 33-month period, 7280 (12.0%) had an operation and 6914 (11.4%) included AAST-defined EGS procedures. There were 4813 (69.6%) surgeries performed laparoscopically. Patients undergoing a laparoscopic procedure tended to be younger (45.7 ± 18.0 years vs. 57.2 ± 17.6, p < 0.001) with similar BMI (29.7 ± 9.0 kg/m2 vs. 28.8 ± 8.3, p < 0.001). Patients in the laparoscopic group had lower mean CCI score (1.6 ± 2.3 vs. 3.4 ± 3.2, p ≤ 0.0001). On multivariable analysis, open surgery had the highest association with inpatient mortality (OR 8.67, 4.23-17.75, p < 0.0001) and at all time points (30-, 90-day, 1-, 3-year). At all time points, conversion to open was found to be a statistically significant protective factor. CONCLUSION: Use of laparoscopy in EGS is common and associated with a decreased risk of all-cause mortality at all time points compared to open procedures. Conversion to open was protective at all time points compared to open procedures.

Platelet Aggregation, Mitochondrial Function and Morphology in Cold Storage: Impact of Resveratrol and Cytochrome c Supplementation.

Donated platelets are critical components of hemostasis management. Extending platelet storage beyond the recommended guidelines (5 days, 22 °C) is of clinical significance. Platelet coagulation function can be prolonged with resveratrol (Res) or cytochrome c (Cyt c) at 4 °C. We hypothesized that storage under these conditions is associated with maintained aggregation function, decreased reactive oxygen species (ROS) production, increased mitochondrial respiratory function, and preserved morphology. Donated platelets were stored at 22 °C or 4 °C supplemented with 50 µM Res or 100 µM Cyt c and assayed on days 0 (baseline), 5, 7 and 10 for platelet aggregation, morphology, intracellular ROS, and mitochondrial function. Declining platelet function and increased intracellular ROS were maintained by Res and Cyt c. Platelet respiratory control ratio declined during storage using complex I + II (CI + CII) or CIV substrates. No temperature-dependent differences (4 °C versus 22 °C) in respiratory function were observed. Altered platelet morphology was observed after 7 days at 22 °C, effects that were blunted at 4 °C independent of exposure to Res or Cyt c. Storage of platelets at 4 °C with Res and Cyt c modulates ROS generation and platelet structural integrity.

Testing strategies for Lynch syndrome in people with endometrial cancer: systematic reviews and economic evaluation.

BACKGROUND: Lynch syndrome is an inherited genetic condition that is associated with an increased risk of certain cancers. The National Institute for Health and Care Excellence has recommended that people with colorectal cancer are tested for Lynch syndrome. Routine testing for Lynch syndrome among people with endometrial cancer is not currently conducted. OBJECTIVES: To systematically review the evidence on the test accuracy of immunohistochemistry- and microsatellite instability-based strategies to detect Lynch syndrome among people who have endometrial cancer, and the clinical effectiveness and the cost-effectiveness of testing for Lynch syndrome among people who have been diagnosed with endometrial cancer. DATA SOURCES: Searches were conducted in the following databases, from inception to August 2019 - MEDLINE ALL, EMBASE (both via Ovid), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (both via Wiley Online Library), Database of Abstracts of Reviews of Effects, Health Technology Assessment Database (both via the Centre for Reviews and Dissemination), Science Citation Index, Conference Proceedings Citation Index - Science (both via Web of Science), PROSPERO international prospective register of systematic reviews (via the Centre for Reviews and Dissemination), NHS Economic Evaluation Database, Cost-Effectiveness Analysis Registry, EconPapers (Research Papers in Economics) and School of Health and Related Research Health Utilities Database. The references of included studies and relevant systematic reviews were also checked and experts on the team were consulted. REVIEW METHODS: Eligible studies included people with endometrial cancer who were tested for Lynch syndrome using immunohistochemistry- and/or microsatellite instability-based testing [with or without mutL homologue 1 (MLH1) promoter hypermethylation testing], with Lynch syndrome diagnosis being established though germline testing of normal (non-tumour) tissue for constitutional mutations in mismatch repair. The risk of bias in studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, the Consolidated Health Economic Reporting Standards and the Philips' checklist. Two reviewers independently conducted each stage of the review. A meta-analysis of test accuracy was not possible because of the number and heterogeneity of studies. A narrative summary of test accuracy results was provided, reporting test accuracy estimates and presenting forest plots. The economic model constituted a decision tree followed by Markov models for the impact of colorectal and endometrial surveillance, and aspirin prophylaxis with a lifetime time horizon. RESULTS: The clinical effectiveness search identified 3308 studies; 38 studies of test accuracy were included. (No studies of clinical effectiveness of endometrial cancer surveillance met the inclusion criteria.) Four test accuracy studies compared microsatellite instability with immunohistochemistry. No clear difference in accuracy between immunohistochemistry and microsatellite instability was observed. There was some evidence that specificity of immunohistochemistry could be improved with the addition of methylation testing. There was high concordance between immunohistochemistry and microsatellite instability. The economic model indicated that all testing strategies, compared with no testing, were cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Immunohistochemistry with MLH1 promoter hypermethylation testing was the most cost-effective strategy, with an incremental cost-effectiveness ratio of £9420 per quality-adjusted life-year. The second most cost-effective strategy was immunohistochemistry testing alone, but incremental analysis produced an incremental cost-effectiveness ratio exceeding £130,000. Results were robust across all scenario analyses. Incremental cost-effectiveness ratios ranged from £5690 to £20,740; only removing the benefits of colorectal cancer surveillance produced an incremental cost-effectiveness ratio in excess of the £20,000 willingness-to-pay threshold. A sensitivity analysis identified the main cost drivers of the incremental cost-effectiveness ratio as percentage of relatives accepting counselling and prevalence of Lynch syndrome in the population. A probabilistic sensitivity analysis showed, at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year, a 0.93 probability that immunohistochemistry with MLH1 promoter hypermethylation testing is cost-effective, compared with no testing. LIMITATIONS: The systematic review excluded grey literature, studies written in non-English languages and studies for which the reference standard could not be established. Studies were included when Lynch syndrome was diagnosed by genetic confirmation of constitutional variants in the four mismatch repair genes (i.e. MLH1, mutS homologue 2, mutS homologue 6 and postmeiotic segregation increased 2). Variants of uncertain significance were reported as per the studies. There were limitations in the economic model around uncertainty in the model parameters and a lack of modelling of the potential harms of gynaecological surveillance and specific pathway modelling of genetic testing for somatic mismatch repair mutations. CONCLUSION: The economic model suggests that testing women with endometrial cancer for Lynch syndrome is cost-effective, but that results should be treated with caution because of uncertain model inputs. FUTURE WORK: Randomised controlled trials could provide evidence on the effect of earlier intervention on outcomes and the balance of benefits and harms of gynaecological cancer surveillance. Follow-up of negative cases through disease registers could be used to determine false negative cases. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019147185. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 42. See the NIHR Journals Library website for further project information.

Lynch syndrome is an inherited condition that is caused by a problem in the genes. People who have Lynch syndrome have a higher risk of some types of cancer (such as bowel and womb cancers) than people who do not have it. Identifying Lynch syndrome could stop cancers developing, lead to earlier treatment for cancers and help to find other family members who might have it. Currently, the National Institute for Health and Care Excellence guidance recommends testing for Lynch syndrome in people who have bowel cancer. Our aim was to investigate whether or not we should test for Lynch syndrome in women with womb cancer, and their relatives. We investigated two main tests: immunohistochemistry and microsatellite instability. There was no clear evidence that one of these tests is better than the other. There is some evidence that both tests are reasonably accurate. There was no good-quality evidence about whether or not treating women with Lynch syndrome with extra cancer screening and aspirin improves their outcomes. We used the best evidence available in our economic model, but it was at high risk of bias. The economic model suggested that testing women with endometrial cancer for Lynch syndrome is cost-effective. The best test in the model was immunohistochemistry followed by methylation testing. We are unsure of these results because of the low quality of evidence available.

Microtubule and tubulin binding and regulation of microtubule dynamics by the antibody drug conjugate (ADC) payload, monomethyl auristatin E (MMAE): Mechanistic insights into MMAE ADC peripheral neuropathy.

Monomethyl auristatin E (MMAE) is a potent anti-cancer microtubule-targeting agent (MTA) used as a payload in three approved MMAE-containing antibody drug conjugates (ADCs) and multiple ADCs in clinical development to treat different types of cancers. Unfortunately, MMAE-ADCs can induce peripheral neuropathy, a frequent adverse event leading to treatment dose reduction or discontinuation and subsequent clinical termination of many MMAE-ADCs. MMAE-ADC-induced peripheral neuropathy is attributed to non-specific uptake of the ADC in peripheral nerves and release of MMAE, disrupting microtubules (MTs) and causing neurodegeneration. However, molecular mechanisms underlying MMAE and MMAE-ADC effects on MTs remain unclear. Here, we characterized MMAE-tubulin/MT interactions in reconstituted in vitro soluble tubulin or MT systems and evaluated MMAE and vcMMAE-ADCs in cultured human MCF7 cells. MMAE bound to soluble tubulin heterodimers with a maximum stoichiometry of ~1:1, bound abundantly along the length of pre-assembled MTs and with high affinity at MT ends, introduced structural defects, suppressed MT dynamics, and reduced the kinetics and extent of MT assembly while promoting tubulin ring formation. In cells, MMAE and MMAE-ADC (via nonspecific uptake) suppressed proliferation, mitosis and MT dynamics, and disrupted the MT network. Comparing MMAE action to other MTAs supports the hypothesis that peripheral neuropathy severity is determined by the precise mechanism(s) of each individual drug-MT interaction (location of binding, affinity, effects on morphology and dynamics). This work demonstrates that MMAE binds extensively to tubulin and MTs and causes severe MT dysregulation, providing convincing evidence that MMAE-mediated inhibition of MT-dependent axonal transport leads to severe peripheral neuropathy.

A systematic review of economic evaluations for donor human milk versus standard feeding in infants.

Reviews on the cost/outcome of donor human milk (DHM) for infants requiring care in the neonatal intensive care unit (NICU) setting have been undertaken. However, the cost-effectiveness evidence is unclear. Therefore, we conducted a systematic review of published full economic evaluations of DHM versus standard feeding in infants in neonatal care with the aim of undertaking a narrative synthesis of the cost-effectiveness evidence and critical appraisal of the methods used. MEDLINE, EMBASE, Web of Science, Cochrane Library, Centre for Reviews and Dissemination (CRD) and PROSPERO databases were searched. Studies were included if they were full economic evaluations (model-based or trial-based), the participants were infants in neonatal units requiring nutritional support, the intervention was DHM and the comparator was any standard feeding option. There were no restrictions on outcome measures. Two authors independently assessed eligibility, extracted data, assessed quality and cross-checked results, with disagreements resolved by consensus. Information extracted focused on study context, and economic evaluation methods and results. Of 2861 studies, seven were included. Six (86%) studies originated from high-income countries. Four (57%) of the studies were model-based. Although we could not directly compare the different studies, due to the heterogenous nature of health and economic parameters used in the studies, all DHM interventions indicated cost-effective or cost saving results. This review suggests that economic evaluation of DHM interventions is an expanding area of research. Although these interventions show promise, future economic evaluations of DHM interventions need to explicitly provide more details on long-term costs and consequences.

Optimizing delivery to meet demand for integrative medicine services in an academic hospital setting: A pilot study.

CONTEXT: A rapidly growing body of evidence shows the positive benefits of integrative medicine (IM) services for patients in hospital-based settings. IM therapies, such as acupuncture, massage, meditation and relaxation, and animal-assisted therapy, reduce symptom burden of pain, anxiety, and stress and increase sense of well-being and satisfaction in hospitalized patients. Current challenges facing hospitals are to move beyond proof-of-concept studies and to provide hospital-based IM therapies. OBJECTIVE: The aim of our quality improvement project was to develop, implement, and evaluate a feasible, scalable, hospital-based "best practice" model for increasing demand for IM services and optimizing their delivery. DESIGN: A multidisciplinary team convened to use quality improvement tools to outline a process for providing IM services. SETTING: A large academic medical center in the Midwestern United States. PARTICIPANTS: IM leadership staff, IM providers, nurses, hospital team members, support staff, and quality improvement staff. INTERVENTIONS: After determining baseline levels of demand and service delivery, we sought to (1) increase nursing staff awareness of available IM services; (2) improve communication between IM providers and nurses; and (3) reinforce communication at the level of nurse supervisors, patients, and family members. MAIN OUTCOME MEASURES: We recorded the numbers and types of IM services ordered at baseline and postimplementation and determined the new delivery rate of requested services. RESULTS: We noted an increase in the number of IM orders, percentage of delivered IM services, and percentage of patients who reported that IM services improved their hospital stay.

Testing for lynch syndrome in people with endometrial cancer using immunohistochemistry and microsatellite instability-based testing strategies - A systematic review of test accuracy.

BACKGROUND: Lynch syndrome is an inherited genetic condition that is associated with an increased risk of cancer, including endometrial and colorectal cancer. We assessed the test accuracy of immunohistochemistry and microsatellite instability-based testing (with or without MLH1 promoter methylation testing) for Lynch syndrome in women with endometrial cancer. METHODS: We conducted a systematic review of literature published up to August 2019. We searched bibliographic databases, contacted experts and checked reference lists of relevant studies. Two reviewers conducted each stage of the review. RESULTS: Thirteen studies were identified that included approximately 3500 participants. None of the studies was at low risk of bias in all domains. Data could not be pooled due to the small number of heterogeneous studies. Sensitivity ranged from 60.7-100% for immunohistochemistry, 41.7-100% for microsatellite instability-based testing, and 90.5-100% for studies combining immunohistochemistry, microsatellite instability-based testing, and MLH1 promoter methylation testing. Specificity ranged from 60.9-83.3% (excluding 1 study with highly selective inclusion criteria) for immunohistochemistry, 69.2-89.9% for microsatellite instability-based testing, and 72.4-92.3% (excluding 1 study with highly selective inclusion criteria) for testing strategies that included immunohistochemistry, microsatellite instability-based testing, and MLH1 promoter methylation. We found no statistically significant differences in test accuracy estimates (sensitivity, specificity) in head-to-head studies of immunohistochemistry versus microsatellite instability-based testing. Reported test failures were rare. CONCLUSIONS: Sensitivity of the index tests were generally high, though most studies had much lower specificity. We found no evidence that test accuracy differed between IHC and MSI based strategies. The evidence base is currently small and at high risk of bias.

Systematic Sonography Looking for Occult Wounds: accuracy of an abdominal ultrasound adjunct in penetrating trauma.

BACKGROUND: Systematic Sonography Looking for Occult Wounds (SSLOW) in trauma is a novel technique for the evaluation of intra-abdominal wounds in penetrating trauma. No data exist regarding the effectiveness. The objective of this study was to evaluate the accuracy of the SSLOW exam. METHODS: This is a prospective collected case series conducted over a period of 10 months and took place at the Accident and Emergency Department (A&E) of the Georgetown Public Hospital Corporation (GPHC). The study enrolled patients presenting to the A&E who were 16 years old or greater with penetrating abdominal trauma. All patients with penetrating trauma received an E-FAST examination. If the E-FAST examination was negative, a SSLOW examination was completed. The sonographer evaluated for free fluid collection between the loops of bowel. The results of the SSLOW were compared to usual care (surgery consult, serial abdominal and E-FAST exams, laparotomy, and 7-day follow-up) and then categorized into four groups: true positive, false positive, true negative, and false negative. These results lead to four categorical values. From these results, sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios were calculated. RESULTS: There were 5 (12%) true positives, 1 (2%) false positive, 37 (86%) true negatives, and zero (0%) false negative. The SSLOW was 100% sensitive (95% CI 5-100%) and 97% specificity (95% CI 74-96%). There was an 80% positive predictive value (95% CI 1.0-64% 95% CI) and 100% negative predictive value (95% CI 88-100%). The positive likelihood ratio was 8.4 (95% CI 3.69-19.1) and negative likelihood ratio was 0. CONCLUSION: The SSLOW examination may be a useful tool in the evaluation of penetrating abdominal injuries.

Plinabulin, an inhibitor of tubulin polymerization, targets KRAS signaling through disruption of endosomal recycling.

Constitutive activation of Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most common oncogenic event in certain types of human cancer and is associated with poor patient survival. Small molecule signaling inhibitors have improved the clinical outcomes of patients with various cancer types but attempts to target KRAS have been unsuccessful. Plinabulin represents a novel class of agents that inhibit tubulin polymerization with a favorable safety profile in clinical trials. In the present study, the potency of plinabulin to inhibit tubulin polymerization and growth of KRAS-driven cancer cells was characterized. In vivo efficacy of plinabulin was tested in two different mouse models; one being the RCAS/t-va gene transfer system and the other being a xenograft model. In vitro cell culture tubulin polymerization assays were used to complement the mouse models. There was improved survival in a KRAS-driven mouse gene transfer glioma model, but lack of benefit in a similar model, without constitutively active KRAS, which supports the notion of a KRAS-specific effect. This survival benefit was mediated, at least in part, by the ability of plinabulin to inhibit tubulin polymerization and disrupt endosomal recycling. It was proposed a mechanism of compromised endosomal recycling of displaced KRAS through targeting microtubules that yields inhibition of protein kinase B, but not extracellular signal regulated kinase (ERK) signaling, therefore lending rationale to combination treatments of tubulin- and ERK-targeting agents in KRAS-driven cancer.

Changing Epidemiology of Catheter-Related Bloodstream Infections in Cancer Patients.

We compared the etiologic organisms of bloodstream infections (BSIs) in cancer patients with central venous catheters (CVCs) between 2 cohorts separated by more than a decade.Gram-negative organisms have become the predominant etiologic organisms of BSIs (52%); they now contribute to 41% of catheter-related BSIs (CRBSIs).Infect Control Hosp Epidemiol 2018;39:727-729.