Impact of abnormal uterine bleeding care in premenopausal patients prior to endometrial malignancy diagnosis.

Background: Literature evaluating the management of abnormal uterine bleeding in premenopausal patients prior to endometrial malignancy diagnosis is lacking. Objective: To evaluate predictors and consequences of inadequate evaluation and management of abnormal uterine bleeding and time to endometrial sampling in premenopausal patients prior to endometrial malignancy diagnosis.Study Design.This was a retrospective cohort study of premenopausal individuals with endometrioid endometrial cancer or atypical hyperplasia at a single institution from 2015 to 2020.. Complete noninvasive management encompassed pelvic exam, ultrasound, and progestin treatment before or in conjunction with the endometrial sampling of diagnosis. Multivariable logistic and ordinal odds models were used to evaluate predictors and outcomes. Results: 152 subjects were included, 80.3 % with cancer and 19.7 % with atypical hyperplasia. The majority of patients had anovulatory bleeding, obesityand recent health care. Only 20.4 % had complete nonvinvasive management, and only 12.5 % had complete noninvasive management or endometrial sampling within 2 months of presentation with abnormal bleeding. Class III obesity reduced the likelihood of complete assessment and increased time to sampling, while age 45 and up and parity reduced time to sampling. Most patients had partial workup but no progestin treatment and long intervals before endometrial sampling after presentation to a provider with abnormal bleeding. Incomplete workup correlated to worse cancer grade and stage. Conclusion: Despite high clinical risk and health care contact, most patients had insufficient gynecologic management preceding a diagnosis of endometrial malignancy. Inadequate care correlated to worse oncologic outcomes and demonstrates missed opportunities for early detection and prevention of endometrial cancer.

Incorporating Industrial By-Products into Geopolymer Mortar: Effects on Strength and Durability.

In recent years, the reuse of industrial waste has become increasingly important for sustainable development. Therefore, this study investigated the application of granulated blast furnace slag (GBFS) as a cementitious replacement material in fly-ash-based geopolymer mortar containing silica fume (GMS). The performance changes in the GMS samples manufactured with different GBFS ratios (0-50 wt%) and alkaline activators were evaluated. The results indicated that GBFS replacement from 0 wt% to 50 wt% significantly affects GMS performance, including improving the bulk density from 2235 kg/m3 to 2324 kg/m3, flexural-compressive strength from 5.83 MPa to 7.29 MPa and 63.5 MPa to 80.2 MPa, respectively; a decrease in water absorption and chloride penetration, and an improvement in the corrosion resistance of GMS samples. The GMS mixture containing 50 wt% GBFS demonstrated the best performances with notable results regarding strength and durability. Owing to the increased production of C-S-H gel, the microstructure of the GMS sample containing more GBFS was denser, as obtained via the scanning electron micrograph analysis results. Incorporating the three industrial by-products into geopolymer mortars was verified when all samples were determined to be in accordance with the relevant Vietnamese standards. The results demonstrate a promising method to manufacture geopolymer mortars that aid sustainable development.

Fear of procedure and pain in individuals considering abortion: A qualitative study.

OBJECTIVES: To explore concerns about procedural abortion and abortion-related pain in a cohort searching for abortion online. METHODS: The Google Ads Abortion Access Study was a national longitudinal cohort study that recruited people searching for abortion online. Participants completed a baseline demographic survey and a follow-up survey four weeks later evaluating barriers and facilitators to abortion. This qualitative study utilized thematic analysis to produce a descriptive narrative based on overarching themes about procedural abortion and abortion-related pain. RESULTS: There were 57 separate mentions from 45 participants regarding procedural abortion or abortion-related pain. We identified two main themes: 1) concerns about the procedure (with subthemes, fear of procedural abortion, comparison to medication abortion, lack of sedation) and 2) abortion-related pain (with subthemes fear of abortion-related pain, experiences of pain, fear of complications and cost-barriers to pain control). CONCLUSIONS: This study highlights the need for improved anticipatory guidance and accessible resources to assuage potential fears and misconceptions regarding abortion. PRACTICE IMPLIACTIONS: Abortion resources, particularly online, should provide accurate and unbiased information about abortion methods and pain to help patients feel more prepared. Providers should be aware of potential concerns surrounding procedural abortion and pain when counseling patients presenting for care.

Profiles of Burnout and Response to the COVID-19 Pandemic Among General Surgery Residents at a Large Academic Training Program.

BACKGROUND: COVID-19 has placed demands on General Surgery residents, who are already at high risk of burnout. This study examined the pandemic's impact on burnout and wellness among General Surgery residents at a large training program. METHODS: General Surgery residents at our institution completed a survey focused on self-reported burnout, mental health, perceptions of wellness resources, and changes in activities during the pandemic. Burnout was measured using the Maslach Burnout Inventory (MBI). Unsupervised machine learning (k-means clustering) was used to identify profiles of burnout and comparisons between profiles were made. RESULTS: Of 82 eligible residents, 51 completed the survey (62% response rate). During COVID-19, 63% of residents had self-described burnout, 43% had depression, 18% acknowledged binge drinking/drug use, and 8% had anxiety. There were no significant differences from pre-pandemic levels (p all >.05). Few residents perceived available wellness resources as effective (6%). Based on MBI scores, the clustering analysis identified three clusters, characterized as "overextended", "engaged", and "ineffective". Engaged residents had the least concerning MBI scores and were significantly more likely to exercise, retain social contact during the pandemic, and had less self-reported anxiety or depression. Research residents were overrepresented in the ineffective cluster (46%), which had high rates of self-reported burnout (77%) and was characterized by the lowest personal accomplishment scores. Rates of self-reported burnout for overextended and engaged residents were 73% and 48%, respectively. CONCLUSION: Surgical residents have high rates of self-reported burnout and depression during the COVID-19 pandemic. Clusters of burnout may offer targets for individualized intervention.

Mortality risk factors in febrile ulceronecrotic Mucha- Habermann disease: A systematic review of therapeutic outcomes and complications.

Febrile Ulceronecrotic Mucha- Habermann Disease (FUMHD) is a variant of Pityriasis Lichenoides Et Varioliformis Acuta (PLEVA). Although rare, the condition may progress to involve serious complications and even lead to fatal outcomes if diagnosis and appropriate treatment is delayed. A PubMed search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIMSA) guidelines was performed to find cases of FUMHD from the earliest records to October 2021. Treatments, complications, and patient outcomes were extracted from the literature and summarized, while a review of quality was also performed. A total of 63 publications with 68 patients were found. Successful treatment modalities for FUMHD included antibiotics, antivirals, systemic steroids, Methotrexate (MTX), cyclophosphamide, Cyclosporine (CYA), Intravenous Immunoglobulins (IVIG), pentoxifylline, and ultraviolet B phototherapy. Out of 68 patients, 55 patients had their condition fully resolved and 13 cases were fatal. Increased age, systemic involvement, and monoclonal T-cell receptor rearrangement were associated with worst prognosis, but mucosal involvement did not affect mortality risk. Overall, the publications had low risk of bias, but most lacked adequate follow-up periods. FUMHD is a diagnostic and therapeutic challenge due to the lack of clearly defined diagnostic criteria and optimum treatment. Further studies with larger patient populations and longer follow-up periods may lead to refinement of diagnostic criteria, establish an optimum treatment regimen, and better estimate the likelihood of recurrence.

Unified in Our Diversity to Address Health Disparities Among Asian Americans, Native Hawaiians, and Pacific Islanders.

The COVID-19 pandemic disproportionately impacted Asian Americans, Native Hawaiians, and Pacific Islanders (AA/NHPIs) in the United States. AA/NHPIs have historically been subjected to discrimination, which was exacerbated by the pandemic. To bring attention to their unique concerns, an AA/NHPI Interest Group of the National Institutes of Health Community Engagement Alliance Against COVID-19 Disparities (CEAL) was formed. This article highlights major concerns raised by the Interest Group: The pervasive and arbitrary practice of data aggregation by public health agencies and health-related researchers, the lack of culturally responsive services in the context of cultural safety, and leadership underrepresentation.

Water-soluble contrast in the management of adhesive small-bowel obstruction: a Canadian centre's experience with guideline development and implementation.

BACKGROUND: Orally administered water-soluble contrast (WSC) can track resolution of small-bowel obstruction (SBO), but no universal pathway for its use exists. We developed and implemented an evidence-based guideline for the use of WSC in the management of adhesive SBO, to be implemented across hospitals affiliated with the University of Toronto. METHODS: We performed a systematic review and created a clinical practice guideline for WSC use in the management of adhesive SBO. The guideline was approved through consensus by an expert panel and implemented in 2018. We performed a prospective cohort study of guideline implementation at 1 pilot site (a large academic tertiary care centre), facilitated by the centre's acute care general surgery service. Primary outcomes included compliance with the guideline and hospital length of stay (LOS). Secondary outcomes included rates of failure of nonoperative management, morbidity, mortality and readmission for recurrence of SBO within 1 year. Patients with adhesive SBO admitted in 2016 served as a control cohort. RESULTS: We analyzed the data for 152 patients with adhesive SBO admitted to the centre, 65 in 2016 (historical cohort), 56 in January-June 2018 (transitional cohort) and 31 in July-December 2018 (implementation cohort). There was a significant increase in compliance with the WSC protocol in 2018, with the proportion of patients receiving WSC increasing from 45% (n = 25) in the transitional cohort to 71% (n = 22) in the implementation cohort (p < 0.001). The median LOS did not differ across the cohorts (p = 0.06). There was a significantly lower readmission rate in the transitional and implementation cohorts (13 [23%] and 9 [29%], respectively) than in the historical cohort (29 [45%]) (p = 0.04). Among patients assigned to nonoperative management initially, a significantly higher proportion of those who received WSC than those who did not receive WSC went on to undergo surgery (14.6% v. 3.6%, p = 0.01), with no difference in median time to surgery (p = 0.2). CONCLUSION: An evidence-based guideline for WSC use in SBO management was successfully developed and implemented; no difference in LOS or time to surgery was seen after implementation, but rates of immediate operation increased and readmission rates decreased. Our experience shows that implementation of an evidence-based clinical practice guideline is feasible through multidisciplinary efforts and coordination.

The Use of Intravenous Lidocaine in the Setting of Chronic Dofetilide Overdose: A Case Report.

Managing the risks and consequences of long QT syndrome can be challenging. Multiple factors contribute to the prolongation of the heart-rate corrected QT (QTc) interval including many drug-drug and drug-disease state interactions. Current literature is often focused on avoiding dysrhythmias with limited guidance on acute management strategies. Here we describe a case of QTc prolongation to 616 msec (Bazett's formula) in the setting of chronic dofetilide overdose due to a possible prescription error. Our case was complicated by alcohol withdrawal and electrolyte disturbances that progressed to patient cardiac arrest in the emergency department. Dofetilide overdose was identified through pharmacist-initiated medication reconciliation and lidocaine was recommended as an alternative to amiodarone during advanced cardiac life support (ACLS). This case highlights the importance of reviewing outpatient medication records as well as avoiding drug-drug interactions during ACLS. Due to the potential for additive QTc prolongation, we recommend using lidocaine as the preferred antiarrhythmic in ACLS algorithms where drug induced QTc prolongation is suspected.

Investigation of the Importance of Protein 3D Structure for Assessing Conservation of Lysine Acetylation Sites in Protein Homologs.

Acetylation is a protein post-translational modification (PTM) that can affect a variety of cellular processes. In bacteria, two PTM Nε-acetylation mechanisms have been identified: non-enzymatic/chemical acetylation via acetyl phosphate or acetyl coenzyme A and enzymatic acetylation via protein acetyltransferases. Prior studies have shown that extensive acetylation of Nε-lysine residues of numerous proteins from a variety of bacteria occurs via non-enzymatic acetylation. In Escherichia coli, new Nε-lysine acetyltransferases (KATs) that enzymatically acetylate other proteins have been identified, thus expanding the repertoire of protein substrates that are potentially regulated by acetylation. Therefore, we designed a study to leverage the wealth of structural data in the Protein Data Bank (PDB) to determine: (1) the 3D location of lysine residues on substrate proteins that are acetylated by E. coli KATs, and (2) investigate whether these residues are conserved on 3D structures of their homologs. Five E. coli KAT substrate proteins that were previously identified as being acetylated by YiaC and had 3D structures in the PDB were selected for further analysis: adenylate kinase (Adk), isocitrate dehydrogenase (Icd), catalase HPII (KatE), methionyl-tRNA formyltransferase (Fmt), and a peroxide stress resistance protein (YaaA). We methodically compared over 350 protein structures of these E. coli enzymes and their homologs; to accurately determine lysine residue conservation requires a strategy that incorporates both flexible structural alignments and visual inspection. Moreover, our results revealed discrepancies in conclusions about lysine residue conservation in homologs when examining linear amino acid sequences compared to 3D structures.

Longer Trials of Non-operative Management for Adhesive Small Bowel Obstruction Are Associated with Increased Complications.

BACKGROUND: Current guidelines for the management of adhesive small bowel obstruction suggest a limited trial of non-operative management, often of 3-5 days. A longer delay to operation may worsen post-operative outcomes in patients who ultimately require operation. Our objective was to evaluate the impact of time to operation on post-operative outcomes in patients who undergo operation following a trial of non-operative management for adhesive small bowel obstruction. METHODS: We used health administrative data to identify patients with adhesive small bowel obstruction who underwent operative management following a trial of non-operative management from 2005 to 2014 in the province of Ontario, Canada. We used multivariable logistic regression to examine the relationship between the time from admission to operation with rates of 30-day mortality, serious complication, and bowel resection. RESULTS: Three thousand five hundred sixty-three patients underwent operation after a trial of non-operative management for adhesive small bowel obstruction. Older patients, patients with a high comorbidity burden, and patients with a lower socioeconomic status were more likely to experience a longer pre-operative period. After adjusting for covariates, each additional day from admission to operation increased odds of serious complication (OR = 1.07, 95% CI = 1.03-1.11) and bowel resection (OR = 1.06, 95% CI = 1.03-1.98). Longer times to operation were not associated with greater adjusted odds of 30-day mortality. CONCLUSION: Each additional day from admission to operation is associated with greater odds of adverse outcomes. Clinical practice guidelines should emphasize strategies that identify patients who will ultimately require operation.

Cleanliness in context: reconciling hygiene with a modern microbial perspective.

The concept of hygiene is rooted in the relationship between cleanliness and the maintenance of good health. Since the widespread acceptance of the germ theory of disease, hygiene has become increasingly conflated with sterilization. In reviewing studies across the hygiene literature (most often hand hygiene), we found that nearly all studies of hand hygiene utilize bulk reduction in bacterial load as a proxy for reduced transmission of pathogenic organisms. This treatment of hygiene may be insufficient in light of recent microbial ecology research, which has demonstrated that humans have intimate and evolutionarily significant relationships with a diverse assemblage of microorganisms (our microbiota). The human skin is home to a diverse and specific community of microorganisms, which include members that exist across the ecological spectrum from pathogen through commensal to mutualist. Most evidence suggests that the skin microbiota is likely of direct benefit to the host and only rarely exhibits pathogenicity. This complex ecological context suggests that the conception of hygiene as a unilateral reduction or removal of microbes has outlived its usefulness. As such, we suggest the explicit definition of hygiene as "those actions and practices that reduce the spread or transmission of pathogenic microorganisms, and thus reduce the incidence of disease."

Chemotherapy induced stroke mimic: 5-Fluorouracil encephalopathy fulfilling criteria for tissue plasminogen activator therapy.

Stroke mimics, especially those involving chemotherapy related neurotoxicity, can confound the clinical diagnosis of acute stroke. Here we describe the case of a 63year-old male with a recent history of stage IIIC colon cancer who presented with confusion on the second day of modified FOLFOX6 (5-fluorouracil/oxaliplatin) chemotherapy and subsequently received alteplase, tissue plasminogen activator therapy (tPA), for presumed ischemic stroke. Magnetic resonance imaging scans after tPA administration did not reveal evidence of an infarction and the patients' neurological symptoms resolved completely after discontinuation of 5-fluorouracil (5-FU). Although this patient did not experience any side effects from tPA, fibrinolytic therapy may have been avoided with a better understanding of potential chemotherapy related adverse reactions. Our experience suggests that 5-FU induced reversible encephalopathy can present with acute stroke-like symptoms and emergency medicine personnel evaluating patients for tPA treatment should be aware of this differential diagnosis.

Electrical Stimulation to Promote Peripheral Nerve Regeneration.

Peripheral nerve injury afflicts individuals from all walks of life. Despite the peripheral nervous system's intrinsic ability to regenerate, many patients experience incomplete functional recovery. Surgical repair aims to expedite this recovery process in the most thorough manner possible. However, full recovery is still rarely seen especially when nerve injury is compounded with polytrauma where surgical repair is delayed. Pharmaceutical strategies supplementary to nerve microsurgery have been investigated but surgery remains the only viable option. Brief low-frequency electrical stimulation of the proximal nerve stump after primary repair has been widely investigated. This article aims to review the currently known biological basis for the regenerative effects of acute brief low-frequency electrical stimulation on axonal regeneration and outline the recent clinical applications of the electrical stimulation protocol to demonstrate the significant translational potential of this modality for repairing peripheral nerve injuries. The review concludes with a discussion of emerging new advancements in this exciting area of research. The current literature indicates the imminent clinical applicability of acute brief low-frequency electrical stimulation after surgical repair to effectively promote axonal regeneration as the stimulation has yielded promising evidence to maximize functional recovery in diverse types of peripheral nerve injuries.

A gender-dependent analysis of Cushing's disease in childhood: pre- and postoperative follow-up.

OBJECTIVE: To analyse gender differences in the clinical presentation and recovery of paediatric patients with Cushing's disease (CD) after transsphenoidal surgery (TSS). Indeed, gender differences between paediatric patients with CD during presentation, after TSS and postoperative recovery have not been adequately studied. DESIGN: Data were obtained and retrospectively analysed from clinical reports and biochemical tests at the time of presentation, 5-9 days after TSS and at the 6 and 12 months postoperative follow-up visits to determine hypothalamic-pituitary-adrenal axis (HPAA) recovery. PATIENTS: Data from 102 paediatric patients (48 females, 54 males, mean age 12.9 ± 3.0) with CD who underwent TSS at the National Institute of Health (NIH) Clinical Center between 1997 and 2011. RESULTS: There was equal distribution of paediatric CD between males and females (53% vs 47%; n = 102, P = 0.484). Males were more likely than females to present with higher mean BMI Z-scores (2.2 ± 0.7 vs 1.9 ± 0.6, P = 0.0079), lower mean height Z-scores (-1.2 ± 1.3 vs -0.7 ± 1.1, P = 0.0467) and higher median plasma ACTH (12.2 vs 8.5 pmol/l; P = 0.0495). Females did not present more frequently with any single sign or symptom. No significant differences were found between males and females for CD cure rates 5-9 days after TSS (87.0% males vs 87.5% females, P = 1.0), long-term cure rates (86.5% vs 93.7%; n = 69; P = 0.4374) and HPAA recovery time (11.2 ± 2.5 vs 11.7 ± 2.5 months; n = 47; P = 0.1992). CONCLUSIONS: Paediatric CD is found to have equal distribution between males and females, but male patients present with elevated BMI and potentially shorter height and higher plasma ACTH. There is no significant difference in the cure rate or HPAA recovery time after TSS between males and females.

Diagnosis of atypical hemolytic uremic syndrome and response to eculizumab therapy.

Atypical hemolytic uremic syndrome (aHUS) has a high mortality rate if not detected and treated early. While in the past, it was associated with renal failure in children, today, it has become increasingly identified among adults. Due to recent advances in the pathogenesis of aHUS and other major thrombotic microangiopathies (TMA), diagnosing it has become a lot easier. We present a case of a 62-year-old man who was initially thought to have thrombotic thrombocytopenic purpura (TTP), but after further evaluation was diagnosed with aHUS. We will discuss how to distinguish aHUS from other major TMA and the role of eculizumab in the management of aHUS.

Syndrome of inappropriate antidiuretic hormone associated with tolterodine therapy.

OBJECTIVE: To present a case of syndrome of inappropriate antidiuretic hormone (SIADH) associated with the use of tolterodine. SETTING: An acute-care unit at a university hospital with a comprehensive program for elders. CASE SUMMARY: In this case report, we present a 99-year-old female who was admitted to our unit for suspected gastrointestinal bleeding who subsequently developed hyponatremia. After the initiation of tolterodine for urinary incontinence, the patient's sodium dropped to 121 mEq/L (from a usual baseline that ranged between 128 mEq/L and 134 mEq/L). Laboratory and urinary findings revealed a serum osmolality of 220 mOsm/kg, a urinary osmolality of 340 mOsm/kg, and a urinary sodium of 101 mmol/L, suggesting a euvolemic hyponatremic state consistent with SIADH. Tolterodine therapy was promptly discontinued, and patient sodium levels normalized. CONCLUSION: Although the etiology of SIADH is often obscure and multifactorial, clinicians should be aware that it is a major cause of hyponatremia among hospitalized elderly patients, and drug therapies must always be evaluated to prevent further complications.

Carbapenem-resistant Klebsiella pneumoniae bacteremia: factors correlated with clinical and microbiologic outcomes.

We undertook a retrospective cohort study describing general outcomes and specific factors associated with positive outcomes in bacteremia due to carbapenem-resistant Klebsiella pneumoniae (CRKP). Forty-eight patients were included, of which 42% died at 30 days. Forty-two percent of patients were in septic shock at the time of the first positive blood culture, and 42% were recipients of solid organ transplants. Lack of microbiologic eradication at 7 days was independently associated with 30-day mortality. Adjunctive procedures performed for source control and microbiologic eradication at 7 days were associated with a favorable clinical response at 7 days. Time to initiation and receipt at any time of antimicrobials with in vitro activity against CRKP were not associated with improved survival. Breakthrough bacteremia occurred in 8 cases, all in patients receiving tigecycline. Our data suggest that severity of illness, rapid microbiologic eradication, and source control are crucial factors in the outcomes of patients with CRKP bacteremia.