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Abnormal Nuclear Membranous Staining Pattern by MLH1 Immunohistochemistry in Endometrial Cancer: A Diagnostic Pitfall and Clone-dependent Artifact
No full textImmunohistochemistry (IHC) for mismatch repair (MMR) proteins is routinely performed for endometrial cancer (EC). Loss of nuclear staining for MLH1/PMS2 triggers reflex testing for MLH1 promoter hypermethylation, while loss of MSH2/MSH6 or isolated loss of MSH6 and PMS2 prompts germline testing for Lynch syndrome. We observed an unusual nuclear membranous staining pattern of MLH1 (clone G168-15). The goal of the study was to determine its significance and highlight this IHC interpretation pitfall. A total of 52 EC cases with abnormal IHC staining patterns were identified in our database from 2017 to 2020. Of these, 41 were reported as MLH1/PMS2 deficient, and 11 as MSH2/MSH6 deficient. On review, 6/41 (14.6%) showed nuclear membranous expression of MLH1 (focal in 1 and diffuse in 5) with complete loss of PMS2 in the same foci. These foci demonstrated mucinous morphology or squamous/morular metaplasia in 3 cases. One additional consultation case showed nuclear membranous staining of MLH1 in the carcinoma and complete loss in the associated endometrial intraepithelial neoplasia, with PMS2 loss in both. Three of 7 cases were FIGO grade 1, and 4 were FIGO grade 2 to 3. MLH1 promoter hypermethylation was detected in 6/7 cases (not performed for one case). Repeat staining with ES05 clone showed complete loss of nuclear MLH1 expression in all 6 in-house cases. Nuclear membranous expression of MLH1 represents an aberrant staining pattern, observed with complete loss of PMS2 and frequently associated with MLH1 promoter hypermethylation. Failure to recognize this aberrant MLH1 expression pattern can lead to misinterpreting isolated PMS2 loss.
Keywords: Carcinoma; Endometrioid; Endometrium; Lynch; Mismatch repair deficiency
Evaluation and management of obstructive sleep apnea in adults hospitalized for medical care: an American Academy of Sleep Medicine clinical practice guideline
No full textIntroduction: The purpose of this guideline is to establish clinical practice recommendations for the management of obstructive sleep apnea (OSA) in medically hospitalized adults.
Methods: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations.
Good practice statement: The following good practice statement is based on expert consensus, and its implementation is necessary for the appropriate and effective management of hospitalized adults with sleep-disordered breathing: For medically hospitalized adults with an established diagnosis of sleep-disordered breathing and on active treatment, existing treatment should be continued rather than withheld, unless contraindicated.
Recommendations: The following recommendations are intended as a guide for clinicians in managing medically hospitalized adults with OSA. Each recommendations statement is assigned a strength ( Strong or Conditional ). A Strong recommendation (i.e., We recommend… ) is one that clinicians should follow under most circumstances. A conditional recommendation (i.e., We suggest… ) is one that requires that the clinician use clinical knowledge and experience and strongly consider the patient\u27s values and preferences to determine the best course of action.
1. For medically hospitalized adults at increased risk for OSA, the AASM suggests in-hospital screening for OSA as part of an evaluation and management pathway that incorporates diagnosis and treatment with positive airway pressure rather than no in-hospital screening. (Conditional recommendation, low certainty of evidence).
Remarks: Screening may include validated questionnaires and/or screening with overnight high-resolution pulse oximetry (HRPO). When considering in-hospital screening as part of a management pathway, 1) patients who place a lower value on the potential reduction of clinically meaningful outcomes (e.g., cardiovascular events) and place a higher value on the possible downsides associated with the use of positive airway pressure (PAP) (e.g., sleep disruption, discomfort), or 2) clinicians who perceive that the diagnosis or management of OSA may interfere with medical care, would reasonably decline OSA screening or PAP during the hospitalization. High risk for OSA is defined by signs and symptoms that suggest moderate to severe OSA (e.g., excessive daytime somnolence + 2 of the following: diagnosed hypertension; habitual loud snoring; witnessed apnea, gasping, or choking and/or association of high-risk comorbidities as outlined in the Figure 1 caption). Diagnostic testing for OSA should ideally be conducted after a patient has been medically stabilized during the hospital stay or post-discharge.
2. For medically hospitalized adults with an established diagnosis of moderate-to-severe OSA and not currently on treatment, the AASM suggests the use of inpatient treatment with positive airway pressure rather than no positive airway pressure. (Conditional recommendation, low certainty of evidence).
Remarks: When considering in-hospital OSA treatment, 1) patients who place a lower value on the potential reduction of clinically meaningful outcomes (e.g., cardiovascular events) and place a higher value on the possible downsides associated with the use of PAP (e.g., sleep disruption, discomfort), or 2) clinicians who perceive that the diagnosis or management of OSA may interfere with medical care, would reasonably decline OSA screening or PAP during the hospitalization.
3. For medically hospitalized adults at increased risk for or with an established diagnosis of OSA, the AASM suggests that sleep medicine consultation be available as part of an evaluation and management pathway, rather than no sleep medicine consultation. (Conditional recommendation, very low certainty of evidence).
Remarks: It is recognized that there will be variability of the availability of hospital-based expertise and resources specific to sleep medicine consultation; therefore, we provide specific guidance as follows. Oversight by a board-certified sleep medicine clinician and/or an AASM-accredited sleep center is preferable. However, elements of this consultation including education and follow-up plan can be provided by those with requisite expertise including advanced practitioners, nurses, sleep technologists, respiratory therapists, care coordinators, case managers, health educators, or other available resource personnel. Given the variability of expertise and resources available, creative consultation models of care such as teleconsult/telehealth, E-consult and/or nursing or respiratory therapist care can be considered. Availability of inpatient diagnostics and treatment as part of the consultation should be taken into consideration in terms of feasibility of implementation of this recommendation.
4. For medically hospitalized adults at increased risk for or with an established diagnosis of OSA, the AASM suggests a discharge management plan to ensure timely diagnosis and effective management of OSA, rather than no plan. (Conditional recommendation, very low certainty of evidence).
Remarks: Consider ordering post-discharge testing or sleep medicine evaluation prior to discharge. Inpatient sleep testing prior to discharge and/or telehealth medicine may be an option to reduce barriers to care. Consider care coordination to ensure appropriate follow-up and post-discharge care.
Keywords: OSA; PAP; hospital; inpatient; obstructive sleep apnea; positive airway pressure; sleep-disordered breathing
Outcomes and Safety of Catheter Ablation in the Elderly
No full textCatheter ablation has emerged as a first-line therapy for many arrhythmias. However, data on the safety and outcomes of catheter ablation in the elderly population remain limited. Here, we aimed to study the outcomes of catheter ablation in octogenarians. The data used in this study were obtained from the National Inpatient Sample database through years 2016-2019. We identified patients ≥80 years old who were diagnosed with atrial fibrillation (AF), atrial flutter (AFL), supraventricular tachycardia (SVT), or ventricular tachycardia (VT) as primary diagnoses. The patients\u27 characteristics and common procedure complications were extracted. We investigated the predictors of mortality and in-hospital complications using multivariable logistic regression. A total of 18,595 patients were included in our analysis. The most common procedure performed was ablation for AF (46%), followed by AFL ablation (23%), VT ablation (18%), and SVT ablation (12%). Higher rates of tamponade (1.6%) were seen in patients undergoing VT ablation. A Charlson\u27s comorbidity index (CCI) score of ≥3 points was used as an independent predictor for complications (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.4-3.3, P = .001). Mortality was higher in VT ablation (4.2%) compared to AFL (1.3%), AF (0.9%), and SVT (0.3%). After logistic regression analysis, a CCI score of ≥3 points (OR, 14.7; 95% CI, 1.88-114.9; P = .01) and tamponade (OR, 4.9; 95% CI, 1.65-14.8; P = .004) were independent predictors of mortality. We found a low incidence of procedural complication rates across all ablation groups in octogenarians. Those undergoing VT ablation were more likely to have complications and a higher mortality rate. Baseline comorbidities can be used to risk-stratify patients when deciding on the best treatment strategy.
Keywords: Catheter ablation; elderly; octogenarians; outcomes
Social media and cytopathology (#cytopath) education: developing a curated online resource index and exploring the evolution of e-learning
No full textIn recent years, social media (SoMe) has revolutionized medical education within the field of pathology; however, its performance in cytopathology has not been explored in detail. This systematic review aims to analyze SoMe trends, hashtag metrics, and online resources within cytopathology over the period of 7 years. A systematic review of 4 databases (PubMed, Medline, Embase, and Scopus) was conducted between January 1st, 2017, and December 22nd, 2022, in order to identify relevant English-language articles about SoMe and cytopathology. An index for online cytopathology (#cytopath) resources was created and posted on Knowledge In Knowledge Out on May 12, 2025. Sixteen studies were included for final analysis, dating from 2017 to 2023. The most commonly cited SoMe platforms used among cytopathologists were X (Twitter) (42%) and Facebook (26%) (P = 0.002). A variety of hashtags were used across posts: #Cytology (24%), #Cytopath (24%), #FNAFriday (24%), #Pathology (16%), and #Cytopathology (12%) (P = 0.865). Two studies discussed the use of SoMe in cytopathology during the COVID-19 pandemic, highlighting its role as a rapid communication tool in times of crisis. The most highly followed cytopathology accounts on X were @cytopathology (10,510), @IACytology (3639), and @britishcytology (3062). This systematic review shows how SoMe is enhancing networking, case discussion, and education in cytopathology. Although it could revolutionize professional communication, it still poses issues regarding privacy and possible misinformation. Future research and guidelines are necessary to optimize the use of SoMe in cytopathology.
Keywords: Cytopathology; Online index; Pathology education; Social media; X (Twitter); e-learning
Pediatric Influenza-Associated Encephalopathy and Acute Necrotizing Encephalopathy - United States, 2024-25 Influenza Season
No full textIn January 2025, CDC received several reports of deaths among children aged \u3c 18 years with a severe form of influenza-associated encephalopathy (IAE) termed acute necrotizing encephalopathy (ANE). Because no national surveillance for IAE currently exists, CDC requested notification of U.S. pediatric IAE cases from clinicians and health departments during the 2024-25 influenza season, a high-severity season with a record number of pediatric influenza-associated deaths. Among 192 reports of suspected IAE submitted to CDC, 109 (57%) were categorized as IAE, 37 (34%) of which were subcategorized as ANE, and 72 (66%) as other IAE; 82 reports did not meet IAE criteria and were categorized as other influenza-associated neurologic disease. The median age of children with IAE was 5 years and 55% were previously healthy, 74% were admitted to an intensive care unit, and 19% died; 41% of children with ANE died. Only 16% of children with IAE who were vaccination-eligible had received the 2024-25 influenza vaccine. Health care providers should consider IAE in children with encephalopathy or altered level of consciousness and a recent or current febrile illness when influenza viruses are circulating. Annual influenza vaccination is recommended for all children aged ≥6 months to prevent influenza and associated complications, potentially including severe neurologic disease such as IAE and ANE
The Clinical Efficacy and Safety of Nintedanib in the Treatment of Interstitial Lung Disease Among Patients With Systemic Sclerosis: Systematic Review
No full textSystemic sclerosis (SSc) is predominantly characterized by an array of cutaneous manifestations including Raynaud\u27s phenomenon, calcinosis, telangiectasias, and skin fibrosis contributing toward substantial morbidity and diminished quality of life. The monumental impact of the disease regarding mortality is due to its pulmonary involvement known as SSc-associated interstitial lung disease (SSc-ILD). Currently, treatment is chiefly directed toward impeding disease progression with the mainstay treatment approaches involving the utilization of cyclophosphamide, mycophenolate mofetil, rituximab, and tocilizumab. Recently, a tyrosine kinase inhibitor, nintedanib, has been approved for the treatment of SSc-ILD and thus became the first medication to be fully licensed for SSc-ILD. A systematic review based on the Preferred Reporting Items of Systematic Review with Meta-analysis (PRISMA) was conducted after successful registration in PROSPERO to evaluate the efficacy and safety of nintedanib in SSc-ILD. We searched PubMed, Scopus, and CENTRAL up to the first of September 2023 utilizing the following keywords: ((Diffuse Parenchymal Lung Disease) OR (Diffuse Parenchymal Lung Diseases) OR (Interstitial Lung Disease) OR (Interstitial Lung Diseases) OR (Interstitial Pneumonia) OR (Interstitial Pneumonitis) OR (Pulmonary Fibrosis)) AND ((Systemic Scleroderma) OR (Systemic Scleroderma)) AND ((BIBF 1120) OR (BIBF-1120) OR (BIBF1120) OR (Nintedanib esylate) OR (Ofev) OR (Vargatef)). The clinical safety profile of nintedanib was deemed more favorable than other therapeutic regimens currently utilized, in addition to adequate clinical efficacy toward SSc-ILD.
Keywords: autoimmune lung disease; scleroderma; systemic sclerosis; tyrosine kinase inhibitor
Outcomes of same-day discharge after left atrial appendage closure with and without pre-discharge transthoracic echocardiography
No full textBackground: Patients with nonvalvular atrial fibrillation with contraindication to anticoagulation undergo Left Atrial Appendage Closure. SCAI/HRS consensus recommends routine post-procedure TTE before same-day discharge. We studied whether there was a difference in outcomes with and without a TTE after device implantation by measuring 45-day hospitalization for any reason.
Methods: We performed a retrospective observational study using the data from our institutional LAAC registry. We compared patients discharged on the same day after the procedure who underwent a TTE vs patients who were discharged without a TTE. The Primary outcome studied was 45-day readmission for any given reason from the day of discharge.
Results: In a Cohort of patients who were discharged on the same day, 350 did not undergo post-procedure TTE, and 60 underwent TTE. 33 patients were readmitted in the TTE group, and 4 patients were readmitted in the No TTE group. The RR for readmission without vs. with pre-discharge TTE was 1.41 (95 % CI 0.52-3.85, p = 0.25). No 45-day mortality occurred in either study group.
Conclusion: For patients undergoing LAAC with same-day discharge, routine TTE before discharge did not significantly influence 45-day readmission rates. Given the absence of clinical benefit but the presence of TTE costs and resource use, a more selective approach to post-procedural imaging should be considered
Library & Knowledge Services Newsletter - Summer 2025
Get PDFLibrary & Knowledge Services Newsletter - Summer 2025https://scholarlycommons.libraryinfo.bhs.org/library_newsletters/1049/thumbnail.jp
Burden of cardiometabolic diseases and depression in a low-income, urban community in Pakistan: a cross-sectional survey
No full textBackground: With the rising epidemic of cardiometabolic diseases (CMDs) in low- and middle-income countries, urban populations face unique challenges such as poor sanitation, environmental pollution, and limited access to healthcare. This study estimates the point prevalence of CMDs and associated risk factors in adults in Karachi, analyses CMD prevalence by sex, and explores the relationship between CMDs and depression.
Methods: A door-to-door survey was conducted in a densely populated urban community within a 0.5 km radius of a primary health centre. A minimum of 1,480 families were required to estimate the prevalence of CMDs. Depression was screened using PHQ-2 and assessed with PHQ-9. Descriptive analyses summarized family-level sociodemographic data. Sex-specific differences in CMD-related risk factors were analysed using χ2 and t-tests. Point prevalence and 95% confidence intervals (CIs) for CMDs were calculated. Bivariate analyses compared cardiometabolic risk factors, healthcare utilization, and mental health across CMD categories. Logistic regression assessed associations between CMDs, demographics, risk factors, and depression.
Results: Of the 1,513 families that participated, 3051 adults were included in the analyses. In this stable community (60% residing for more than five years), there was high Urdu (91%) and English (76%) literacy. There was high cell phone ownership (90%) and internet use (81%). Hypertension was the most prevalent CMD (34%). The likelihood of CMD increased with age, rising 49.39 times (95% CI: 30.21 - 80.74; p: \u3c 0.001) higher in those 60 years and above than those aged 18-29. CMD prevalence was strongly associated with depression, compared to those with no CMDs, there were significantly higher odds of mild (OR: 1.89; 95% CI: 1.28 - 2.78; p: \u3c 0.001) and moderate (OR: 2.21; 95%CI: 1.17 - 4.17; p: \u3c 0.014) depression among participants with CMDs. Median health expenditure was 14.2% (IQR: 11.4-26.7%) of monthly income, with increasing CMD burden linked to higher rates of delay in purchasing medications (p: \u3c 0.001).
Conclusion: This study highlights the significant burden of CMDs, multimorbidity, and depression in a low-income urban community in Pakistan. The findings suggest that a cardiometabolic multimorbidity (CMM) epidemic is emerging in urban Pakistan, emphasizing the need for integrated interventions addressing physical, mental, economic, and environmental factors in CMD management.
Keywords: Cardiometabolic diseases; Cardiometabolic multimorbidity; Depression; Low-middle income country; Urban community
Optical Coherence Tomography vs. Angiography Alone to Guide PCI for Complex Lesions: A Meta-Analysis of Randomized Controlled Trials
No full textBackground: Optical coherence tomography (OCT) provides high-resolution intracoronary imaging. However, whether the addition of OCT to angiography to guide percutaneous coronary intervention (PCI) of complex lesions affects clinical outcomes is debated. Methods: A systematic search for randomized controlled trials (RCTs) was conducted using PubMed, Scopus, and Cochrane databases through September 2024. Endpoints included major adverse cardiovascular events (MACE), cardiac death, myocardial infarction (MI), periprocedural MI, all-cause mortality, stent thrombosis (definite or probable), and target vessel revascularization (TVR). The random-effects model was used to generate risk ratios (RRs) and 95% confidence intervals (CIs). Results: A literature search identified 4 RCTs including 5,603 patients with a median follow-up of 2 years. Compared with PCI guided by angiography alone, OCT-guided PCI was associated with lower MACE (RR 0.68; 95%CI 0.55-0.84; p\u3c0.001), cardiac death (RR 0.43; 95%CI 0.24-0.76; p=0.003), MI (RR 0.75; 95%CI 0.59-0.96; p=0.02), all-cause mortality (RR 0.58; 95% CI 0.38-0.87; p=0.009, and stent thrombosis (RR 0.49; 95% CI 0.26-0.90; p=0.02). There was a trend toward lower TVR (RR 0.67; 95% CI 0.44-1.03; p=0.07) and lower periprocedural MI (RR 0.79; 95% CI 0.59-1.06; p=0.11) with OCT guidance compared to angiography alone. Conclusions: The addition of OCT guidance to PCI of complex lesions resulted in better clinical outcomes than angiography guidance alone. Updated guidelines should strengthen recommendations supporting the use of OCT guidance for complex PCI