Eukaryotic initiation factor 4B is a multi-functional RNA binding protein that regulates histone mRNAs.

RNA binding proteins drive proliferation and tumorigenesis by regulating the translation and stability of specific subsets of messenger RNAs (mRNAs). We have investigated the role of eukaryotic initiation factor 4B (eIF4B) in this process and identify 10-fold more RNA binding sites for eIF4B in tumour cells from patients with diffuse large B-cell lymphoma compared to control B cells and, using individual-nucleotide resolution UV cross-linking and immunoprecipitation, find that eIF4B binds the entire length of mRNA transcripts. eIF4B stimulates the helicase activity of eIF4A, thereby promoting the unwinding of RNA structure within the 5' untranslated regions of mRNAs. We have found that, in addition to its well-documented role in mRNA translation, eIF4B additionally interacts with proteins associated with RNA turnover, including UPF1 (up-frameshift protein 1), which plays a key role in histone mRNA degradation at the end of S phase. Consistent with these data, we locate an eIF4B binding site upstream of the stem-loop structure in histone mRNAs and show that decreased eIF4B expression alters histone mRNA turnover and delays cell cycle progression through S phase. Collectively, these data provide insight into how eIF4B promotes tumorigenesis.

ChatGPT, Bard, and Bing Chat are large language processing models that answered OITE questions with a similar accuracy to first-year orthopaedic surgery residents.

PURPOSE: To assess ChatGPT, Bard, and BingChat's ability to generate accurate orthopaedic diagnosis or corresponding treatments by comparing their performance on the Orthopaedic In-Training Examination (OITE) to orthopaedic trainees. METHODS: OITE question sets from 2021 and 2022 were compiled to form a large set of 420 questions. ChatGPT (GPT3.5), Bard, and BingChat were instructed to select one of the provided responses to each question. The accuracy of composite questions was recorded and comparatively analyzed to human cohorts including medical students and orthopaedic residents, stratified by post-graduate year. RESULTS: ChatGPT correctly answered 46.3% of composite questions whereas BingChat correctly answered 52.4% and Bard correctly answered 51.4% of questions on the OITE. Upon excluding image-associated questions, ChatGPT, BingChat, and Bard's overall accuracies improved to 49.1%, 53.5%, and 56.8%, respectively. Medical students and orthopaedic residents (PGY1-5) correctly answered 30.8%, 53.1%, 60.4%, 66.6%, 70.0%, and 71.9%, respectively. CONCLUSION: ChatGPT, Bard, and BingChat are AI models that answered OITE questions with an accuracy similar to that of first-year orthopaedic surgery residents. ChatGPT, Bard, and BingChat achieved this result without using images or other supplementary media that human test takers are provided.

A Public Mid-Density Genotyping Platform for Hexaploid Sweetpotato (Ipomoea batatas [L.] Lam).

Small public breeding programs focused on specialty crops have many barriers to adopting technology, particularly creating and using genetic marker panels for genomic-based decisions in selection. Here, we report the creation of a DArTag panel of 3120 loci distributed across the sweetpotato (Ipomoea batatas [L.] Lam) genome for molecular-marker-assisted breeding and genomic prediction. The creation of this marker panel has the potential to bring cost-effective and rapid genotyping capabilities to sweetpotato breeding programs worldwide. The open access provided by this platform will allow the genetic datasets generated on the marker panel to be compared and joined across projects, institutions, and countries. This genotyping resource has the power to make routine genotyping a reality for any breeder of sweetpotato.

Secosteroid diacylhydrazines as novel effective agents against hormone-dependent breast cancer cells.

This research aimed to develop novel selective secosteroids that are highly active against hormone-dependent breast cancer. A simple and convenient approach to N'-acylated 13,17-secoestra-1,3,5(10)-trien-17-oic acid hydrazides was disclosed and these novel types of secosteroids were screened for cytotoxicity against the hormone-dependent human breast cancer cell line MCF7. Most secosteroid N'-benzoyl hydrazides have demonstrated high cytotoxicity against MCF7 cells with IC50 values below 5µM, which are superior to that of the reference drug cisplatin. Hit compounds 2c, 2e and 2i were characterized by high cytotoxicity (IC50 = 1.6-1.9µM) and very good selectivity towards MCF7 breast cancer cells. The lead secosteroids 2c, 2e and 2i also exhibit antiestrogenic effects and alter the expression of cell cycle regulating proteins. The effect of selected compounds on PARP (poly(ADP-ribose) polymerase) and Bcl-2 (B-cell CLL/lymphoma 2) indicates their proapoptotic potential. The synthesized secosteroids may be considered as new promising anti-breast cancer agents targeting ERα and apoptosis pathways.

Methodological Approaches for Increasing the Retroviral Transduction Efficiency of Primary NK Cells.

BACKGROUND: The growing attention to NK cells for cancer cell therapy is associated with the need to establish highly efficient protocols for their genetic modification, particularly by retroviral transduction. OBJECTIVE: In this work, we have optimized several stages of the retroviral-based modification process, and determined the distribution of the amino acid transporter ASCT2 between NK cell subsets. METHODS: Retroviral particles were produced using the Phoenix Ampho cell line transfected with the calcium phosphate method . We used RD114-based retroviral transduction for lymphocyte cell lines and primary NK cells. RESULTS: We have determined the optimal time to collect the RD114-pseudotyped viral supernatants resulting in the titer of viral particles required for efficient NK cell modification to be between 48 and 72 hours. Retroviral modification by retronectin-based method did not alter NK cell functional activity and cell survival. We identified differences in the Multiplicity of Infection (MOI) among cell lines that were partially associated with the ASCT2 surface expression. Cells with higher ASCT2 levels were more susceptible to transduction with RD114-pseudotyped viral particles. Higher ASCT2 expression levels were revealed in activated CD57+ and KIR2DL2DL3+ NK cells compared to their negative counterparts. CONCLUSION: Our findings provide a more nuanced understanding of NK cell transduction, offering valuable insights for improving therapeutic applications involving NK cell modification.

A Rare Placental Site Nodule Involving the Ovary.

Placental site nodule (PSN) is a benign lesion representing a nodular aggregate of intermediate trophoblast, embedded in a hyalinized stroma, thought to arise from noninvoluted placental site remaining from a past gestation. Uterus is the most common site of PSN. Occurrence in extrauterine sites is rare, with most examples being reported in the fallopian tubes. Here we report an example of PSN in the ovary. A 35-year-old woman, gravida 4, para 1, with history of adnexal ectopic pregnancy treated with methotrexate, at 39 weeks and 1 day of a subsequent pregnancy, underwent a scheduled C-section. The surgery was successful, and a healthy female infant was delivered. Intraoperative adnexal inspection revealed a small pedunculated mass on the right ovary, which was excised and sent for pathological examination. Gross inspection showed a soft, tan-white tissue fragment measuring 2.0 × 1.0 × 0.2 cm. Microscopic examination showed epithelioid cells with hyperchromatic, mildly atypical nuclei and abundant eosinophilic cytoplasm, embedded in a hyalinized stroma, forming a nodule. A diagnosis of placental site nodule was made. Immunohistochemical stains for keratin AE1/AE3, vimentin, and inhibin were strongly positive in the epithelioid cells, and immunostain for p63 was focally positive, supporting the diagnosis. PSN of the ovary is extremely rare. To our knowledge, there has been only one reported patient in the literature so far. Extrauterine PSNs are thought to arise from ectopic pregnancies. Our patient's ovarian PSN is most likely a consequence of her previous adnexal ectopic pregnancy, which was treated medically.

The Use of Breast-specific Gamma Imaging as a Low-Cost Problem-Solving Strategy for Avoiding Biopsies in Patients With Inconclusive Imaging Findings on Mammography and Ultrasonography.

OBJECTIVE: To evaluate the clinical performance and financial costs of breast-specific gamma imaging (BSGI) as a biopsy-reducing problem-solving strategy in patients with inconclusive diagnostic imaging findings. METHODS: A retrospective analysis of all patients for whom BSGI was utilized for inconclusive imaging findings following complete diagnostic mammographic and sonographic evaluation between January 2013 and December 2018 was performed. Positive BSGI findings were correlated and biopsied with either US or stereotactic technique with confirmation by clip location and pathology. After a negative BSGI result, patients were followed for a minimum of 24 months or considered lost to follow-up and excluded (22 patients). Results of further imaging studies, biopsies, and pathology results were analyzed. Net savings of avoided biopsies were calculated based on average Medicare charges. RESULTS: Four hundred and forty female patients from 30 to 95 years (mean 55 years) of age were included in our study. BSGI demonstrated a negative predictive value (NPV) of 98.4% (314/319) and a positive predictive value for biopsy of 35.5% (43/121). The overall sensitivity was 89.6% (43/48), and the specificity was 80.1% (314/392). In total, 78 false positive but only 5 false negative BSGI findings were identified. Six hundred and twenty-one inconclusive imaging findings were analyzed with BSGI and a total of 309 biopsies were avoided. Estimated net financial savings from avoided biopsies were $646 897. CONCLUSION: In the management of patients with inconclusive imaging findings on mammography or ultrasonography, BSGI is a problem-solving imaging modality with high NPV that helps avoid costs of image-guided biopsies.

Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy.

BACKGROUND: Neoadjuvant therapy improves recurrence-free survival (RFS) in resectable stage III cutaneous melanoma. However, accurately predicting individual recurrence risk remains a significant challenge. We investigated circulating tumour DNA (ctDNA) as a biomarker for recurrence in measurable stage IIIB/C melanoma patients undergoing neoadjuvant immunotherapy. METHODS: Plasma samples were collected pre-neoadjuvant treatment, pre-surgery and/or six weeks post-surgery from 40 patients enrolled in the OpACIN-neo and PRADO clinical trials. Patients received two cycles of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) before surgery. Cell free DNA (cfDNA) underwent unbiased pre-amplification followed by tumour-informed mutation detection using droplet digital polymerase chain reaction (ddPCR) with the Bio-Rad QX600 PCR system. RESULTS: Pre-treatment ctDNA was detectable in 19/40 (48%) patients. Among these, 17/19 (89%) zero-converted within six weeks of surgery and none recurred. Positive ctDNA post-surgery (N = 4), irrespective of pre-treatment ctDNA status, was 100% predictive of recurrence (sensitivity 44%, specificity 100%). Furthermore, ctDNA cleared prior to surgery in 7/9 (78%) patients who did not recur, warranting further investigation into ctDNA-guided surgical management. CONCLUSION: Post-surgery ctDNA positivity and zero-conversion are highly predictive of recurrence, offering a window for personalised modification of adjuvant therapy.

Clinical response and pathway-specific correlates following TIGIT-LAG3 blockade in myeloma: the MyCheckpoint randomized clinical trial.

Persons with myeloma were randomized to receive an anti-TIGIT (T cell immunoreceptor) or anti-LAG3 (lymphocyte activation gene) antibody followed by combination with pomalidomide and dexamethasone ( NCT04150965 ). Primary and secondary endpoints were safety and efficacy, respectively. Therapy was well tolerated without dose-limiting toxicity. Durable clinical responses were observed in both the anti-TIGIT(three of six participants) and the anti-LAG3 (two of six participants) arms. Anti-LAG3 responders had higher naive cluster of differentiation 4 (CD4)-positive T cells and lower programmed cell death protein 1-positive effector T cells. Anti-TIGIT responders had higher CD226 expression, natural killer cell activation and lower CD112 expression. These data demonstrate the clinical activity of TIGIT-LAG3 blockade and identify pathway-specific response correlates in myeloma.

CSU-ALS Certified Centers are Associated with Improved Failure to Rescue After Cardiac Arrest: A Propensity Score Match Analysis.

OBJECTIVE: The impact of Cardiac Surgical Unit - Advanced Life Support (CSU-ALS) training on failure to rescue after cardiac arrest (FTR-CA) is unknown. We hypothesized that institutional CSU-ALS certification would be associated with lower FTR-CA. METHODS: Patients undergoing Society of Thoracic Surgeons (STS) index operations from 2020-2023 from a regional collaborative were analyzed. Each institution was surveyed regarding its status as a CSU-ALS certified center. Patients stratified by CSU-ALS certification were 1:1 propensity score matched with subsequent multivariable model reviewing associations with failure to rescue after cardiac arrest. RESULTS: A total of 12209 patients were included in the study period across 15 institutions. Eight centers reported CSU-ALS certification. After propensity score matching, two patient cohorts were formed (n = 3557). Patients at CSU-ALS centers had higher rates of ICU readmission (3.9% vs 2.3%, p<0.01) and total OR time (340 min vs 323 min, p<0.01). Hospital readmission was less likely in the CSU-ALS centers (9.0% vs 10.1%, p <0.01). There was no difference in the rate of post-operative cardiac arrest (1.8% vs 2.2 %, p = 0.24) or operative mortality (2.5% vs 2.9%, p = 0.30). After risk-adjustment, CSU-ALS centers (OR 0.30 [CI 0.12 - 0.72], p <0.01) and higher-volume centers (OR 0.15 [CI 0.03 - 0.74], p = 0.02) had reduced odds of FTR after cardiac arrest. CONCLUSIONS: Centers with CSU-ALS certification are associated with a lower risk-adjusted likelihood of FTR after cardiac arrest. This highlights the importance of well-trained staff and treatment algorithms in the care of post-operative cardiac surgery patients.

Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): long-term, health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial.

BACKGROUND: In the European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 study, adjuvant pembrolizumab improved recurrence-free survival and distant-metastasis-free survival in patients with resected stage III melanoma. Earlier results showed no effect of pembrolizumab on health-related quality of life (HRQOL). Little is known about HRQOL after completion of treatment with pembrolizumab, an important research area concerning patients who are likely to become long-term survivors. This study reports long-term HRQOL results. METHODS: This double-blind, randomised, controlled, phase 3 trial compared adjuvant pembrolizumab with placebo in patients aged 18 years or older with previously untreated stage IIIA, IIIB, or IIIC resected cutaneous melanoma and an Eastern Cooperative Oncology Group performance status score of 1 or 0, recruited from 123 academic centres and community hospitals in 23 countries. Patients were randomly assigned (1:1) with a minimisation technique stratified for stage and geographical region to receive 200 mg of intravenous pembrolizumab or placebo every 3 weeks for up to 18 doses. Investigators, patients, and those collecting or analysing data were masked to group assignment. The primary endpoint of the trial was recurrence-free survival (reported elsewhere). HRQOL was a prespecified exploratory endpoint, measured with the EORTC Quality of Life Questionnaire-Core 30. All patients with a baseline HRQOL evaluation available who were alive 108 weeks from randomisation were included in this analysis of long-term HRQOL. Long-term HRQOL included assessments measured every 6 months between 108 weeks and 48 months after randomisation. The threshold of clinical relevance for all HRQOL scales used was an average change of 5 points. The trial is ongoing, recruitment is completed, and HRQOL data collection is finalised. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37. FINDINGS: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were randomly assigned to pembrolizumab (n=514) or placebo (n=505). Completion of the HRQOL evaluation at baseline exceeded 90% (481 [94%] patients in the pembrolizumab group and 467 [92%] in the placebo group), and ranged between 60% and 90% for post-baseline timepoints. Among patients with a baseline HRQOL evaluation, 365 (39%) were female and 583 (61%) were male. The mean change from baseline to long-term HRQOL was -0·56 (95% CI -2·33 to 1·22) in the pembrolizumab group and 1·63 (-0·12 to 3·38) in the placebo group. The difference between the two groups was -2·19 (-4·65 to 0·27, p=0·081). Differences for all other scales were smaller than 5 and not statistically significant. INTERPRETATION: Adjuvant pembrolizumab did not have a significant impact on long-term HRQOL compared with placebo in patients with resected stage III melanoma. These findings, together with earlier results on efficacy and HRQOL, support the use of pembrolizumab in this setting. FUNDING: Merck Sharp & Dohme.

Identification of Succinate Dehydrogenase Gene Variant Carriers by Blood Biomarkers.

Background: Carriers of germline pathogenic variants (PVs) in succinate dehydrogenase genes (SDHx) are at risk of developing tumors, including paragangliomas, gastrointestinal stromal tumors, and renal cell carcinomas. Early tumor detection is paramount for improved clinical outcome. Blood-based biomarkers could aid in identifying individuals with PVs early and provide functional evidence in patients with variants of unknown significance. Methods: Blood plasma, urine, peripheral blood mononuclear cells, and erythrocytes from patients with and without SDHx PVs were investigated for central carbon metabolites. These were measured by liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy and included among others, succinate, fumarate, α-ketoglutarate, and lactate. Results: Plasma succinate to fumarate ratios effectively distinguished tumor-bearing and asymptomatic patients with and without SDHx PV with promising diagnostic performance (areas under the receiver operating characteristic curve 0.86-0.95), although higher levels were noted in individuals with SDHB PV. Metabolites in urine and in peripheral blood mononuclear cell extracts were largely similar between groups. Erythrocytes showed strong metabolic alterations in patients with SDHx PV compared to controls, with 8 of 13 low-molecular organic acids being significantly different (P < .05). The lactate-α-ketoglutarate-ratio of erythrocytes identified individuals with SDHx PV equally well as plasma, with a sensitivity and specificity of 92% (AUC 0.97). Conclusion: Blood biomarkers have been underutilized for identifying carriers of SDHx PV or to validate variants of unknown significance. Our findings advocate for further investigation into a combined approach involving plasma and erythrocytes for future diagnostic strategies.

A biomechanical study comparing the compression force and osseous area of contact of two screws fixation techniques used in ankle joint arthrodesis model.

INTRODUCTION: Arthrodesis of a (diseased) ankle joint is usually performed to achieve pain relief and stability. One basic principle of arthrodesis techniques includes rigid fixation of the surfaces until union. It seems plausible that stable anchoring and homogeneous pressure distribution should be advantageous, however, it has not been investigated yet. The aim is to achieve uniform compression, as this is expected to produce favorable results for the bony fusion of the intended arthrodesis. Numerous implants with different biomechanical concepts can be used for ankle fusion. In this study, headless compression screws (HCS, DePuy Synthes, Zuchwil, Switzerland) were compared biomechanically to an alternative fixation System, the IOFix device (Extremity Medical, Parsippany, NJ, USA) in regard to the distribution of the compression force (area of contact) and peak compression in a sawbone arthrodesis-model (Sawbones® Pacific Research Laboratories, Vashon, WA, USA). This study aims to quantify the area of contact between the bone interface that can be obtained using headless compression screws compared to the IOFix. In current literature, it is assumed, that a large contact surface with sufficient pressure between the bones brings good clinical results. However, there are no clinical or biomechanical studies, that describe the optimal compression pressure for an arthrodesis. MATERIAL AND METHODS: Two standardized sawbone blocks were placed above each other in a custom-made jig. IOFix and headless compression screws were inserted pairwise parallel to each other using a template for a uniform drilling pattern. All screws were inserted with a predefined torque of 0.5 Nm. Pressure transducers positioned between the two sawbone blocks were compressed for the measurement of peak compression force, compression distribution, and area of contact. RESULTS: With the IOFix, the compression force was distributed over significantly larger areas compared to the contact area of the HCS screws, resulting in a more homogenous contact area over the entire arthrodesis surface. Maximum compression force showed no significant difference. CONCLUSION: The IOFix system distributes the compression pressure over a much larger area, resulting in more evenly spread compression at the surface. Clinical studies must show whether this leads to a lower pseudarthrosis rate.

Overcoming ABCB1 mediated multidrug resistance in castration resistant prostate cancer.

Prostate cancer (PCa) is the second leading cause of cancer-related death in American men. PCa that relapses after hormonal therapies, referred to as castration resistant PCa (CRPC), often presents with metastases (mCRPC) that are the major cause of mortality. The few available therapies for mCRPC patients include taxanes docetaxel (DTX) and cabazitaxel (CBZ). However, development of resistance limits their clinical use. Mechanistically, resistance arises through upregulation of multidrug resistance (MDR) proteins such as MDR1/ABCB1, making ABCB1 an attractive therapeutic target. Yet, ABCB1 inhibitors failed to be clinically useful due to low specificity and toxicity issues. To study taxanes resistance, we produced CBZ resistant C4-2B cells (RC4-2B) and documented resistance to both CBZ and DTX in cell culture and in 3D prostaspheres settings. RNAseq identified increased expression of ABCB1 in RC4-2B, that was confirmed by immunoblotting and immunofluorescent analysis. ABCB1-specific inhibitor elacridar reversed CBZ and DTX resistance in RC4-2B cells, confirming ABCB1-mediated resistance mechanism. In a cell-based screen using a curated library of cytotoxic drugs, we found that DNA damaging compounds Camptothecin (CPT) and Cytarabine (Ara-C) overcame resistance as seen by similar cytotoxicity in parental C4-2B and resistant RC4-2B. Further, these compounds were cytotoxic to multiple PC cells resistant to taxanes with high ABCB1 expression and, therefore, can be used to conquer the acquired resistance to taxanes in PCa. Finally, inhibition of cyclin-dependent kinases 4/6 (CDK4/6) with small molecule inhibitors (CDK4/6i) potentiated cytotoxic effect of CPT or Ara-C in both parental and resistant cells. Overall, our findings indicate that DNA damaging agents CPT and Ara-C alone or in combination with CDK4/6i can be suggested as a new treatment regimen in CRPC patients, including those that are resistant to taxanes.

Statistical primer: propensity scores used as overlap weights provide exact covariate balance.

Overlap weighting (OW), using weights defined as the probability of receiving the opposite treatment, is a relatively new, alternative propensity score (PS)-based weighting technique used to adjust for confounding when estimating causal treatment effects. It has preferable properties compared to inverse probability of treatment weighting (IPTW) such as exact covariate balance, safeguards against extreme weights, and emphasis on medical equipoise, where treatment decisions are most uncertain. In this article we introduce the OW methodology, compare it to IPTW, and provide some strategies for assessing weighting impact, through an applied example of hospital mortality. When the PS distributions have large separation, IPTW has been shown to produce biased and less efficient estimates of the treatment effect, making OW a preferred method in such cases.

Generative artificial intelligence performs rudimentary structural biology modeling.

Natural language-based generative artificial intelligence (AI) has become increasingly prevalent in scientific research. Intriguingly, capabilities of generative pre-trained transformer (GPT) language models beyond the scope of natural language tasks have recently been identified. Here we explored how GPT-4 might be able to perform rudimentary structural biology modeling. We prompted GPT-4 to model 3D structures for the 20 standard amino acids and an α-helical polypeptide chain, with the latter incorporating Wolfram mathematical computation. We also used GPT-4 to perform structural interaction analysis between the anti-viral nirmatrelvir and its target, the SARS-CoV-2 main protease. Geometric parameters of the generated structures typically approximated close to experimental references. However, modeling was sporadically error-prone and molecular complexity was not well tolerated. Interaction analysis further revealed the ability of GPT-4 to identify specific amino acid residues involved in ligand binding along with corresponding bond distances. Despite current limitations, we show the current capacity of natural language generative AI to perform basic structural biology modeling and interaction analysis with atomic-scale accuracy.

Chimeric Antigen Receptor (CAR) T-Cell Therapy Use in Patients with Multiple Myeloma and Kidney Failure on Maintenance Hemodialysis: A Report of 2 Cases.

Chimeric antigen receptor (CAR) T-cell therapy against B-cell maturation antigen is a new treatment modality for relapsed or refractory multiple myeloma (MM). Patients with kidney failure and MM were excluded from the pivotal CAR T-cell therapy clinical trials: KaRMMa (idecabtagene vicleucel) and CARTITUDE (ciltacabtagene autocleucel). The safety and efficacy of CAR T-cell therapy in patients with relapsed or refractory MM and kidney failure are limited to a few case reports using idecabtagene vicleucel. Here, we report the first 2 cases of ciltacabtagene autoleucel use in patients with kidney failure on maintenance hemodialysis and relapsed or refractory MM. Both patients achieved a hematologic response following ciltacabtagene autoleucel administration without serious adverse events. These findings suggest that ciltacabtagene autoleucel may be safe and effective in patients with relapsed or refractory MM and kidney failure. In this report, we review the available literature regarding the use of CAR T-cell therapy in patients with MM and kidney failure. We also discuss the modification of the lymphodepletion regimen in the kidney failure setting.

Implementation of a Standardized Protocol for Recurrent Laryngeal Nerve Monitoring Reduces False Negative Results During Neck Surgery: A Quality Control Case Study.

Recurrent laryngeal nerve (RLN) injury during neck surgery can cause significant morbidity related to vocal cord (VC) dysfunction. VC electromyography (EMG) is used to aid in the identification of the RLN and can reduce the probability of inadvertent surgical injury. Errors in the placement of specialized EMG endotracheal tubes (ETT) can result in unreliable signals, false-negative responses, or no response when stimulating the RLN. We describe a novel educational protocol developed to optimize uniformity in the placement of ETTs to improve the reliability of RLN monitoring. An intraoperative neuromonitoring database was queried for all neck surgeries requiring RLN monitoring. Data points extracted for all cases requiring EMG monitoring for neck procedures. Free running and stimulated EMG were monitored and continuously recorded by a certified technologist. Alerts were compared between 2013-14 and 2015-18 using a two-sample test of proportions. Significant reductions in alerts were demonstrated after protocol implementation (7.5% pre-implementation to 2.1% post). Alerts were compared between 2013-14 (overall alert rate of 1.8%, pre-implementation period) and 2015-18 (overall alert rate of 2.8%, post-implementation period). Protocolization for placement of EMG-ETT improved accuracy in EMG monitoring. In the follow-up cohort of 1,080 patients, use of this protocol continued to reduce the rate of alerts related to ETT malposition, confirming the sustainability of this intervention through routine education. The risk of nerve injury is reduced when the rate of alerts is minimized. Scheduled or continuous protocol education of anesthesia personnel should continue to ensure compliance with protocol.

Safety of thyroidectomy in hospitalized patients: A descriptive analysis of the NSQIP thyroidectomy-targeted data.

BACKGROUND: Some patients undergo thyroidectomy while hospitalized for a related or independent indication. Outcomes have not been described in this group. METHODS: The 2016-2018 thyroidectomy-targeted NSQIP datasets were queried for patients admitted for ≥1 day preoperatively. 1:1 propensity score matching was employed to compare the outcomes of admitted patients to outpatients, including surgical and thyroidectomy-specific outcomes. Multivariable logistic regression determined factors associated with poor outcomes. RESULTS: Of 18,078 patients, 312 were admitted at least 1 day prior to surgery. Inpatients had higher ASA classifications and rates of several comorbidities compared to the general population. After propensity score matching, inpatients had higher rates of overall complications, unplanned reoperation, and bleeding. They also experienced higher rates of thyroidectomy-specific complications such as hypocalcemia and neck hematoma. By multivariable regression, admission prior to surgery was associated with development of any complications. CONCLUSION: Thyroidectomy in hospitalized patients carries an increased risk of complications. Patients requiring thyroidectomy while already hospitalized should be counseled accordingly.