Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions.

Advancing age is associated with several age-related diseases (ARDs), with musculoskeletal conditions impacting millions of elderly people worldwide. With orthopedic conditions contributing towards considerable number of patients, a deeper understanding of bone aging is the need of the hour. One of the underlying factors of bone aging is cellular senescence and its associated senescence associated secretory phenotype (SASP). SASP comprises of pro-inflammatory markers, cytokines and chemokines that arrest cell growth and development. The accumulation of SASP over several years leads to chronic low-grade inflammation with advancing age, also known as inflammaging. The pathways and molecular mechanisms focused on bone senescence and inflammaging are currently limited but are increasingly being explored. Most of the genes, pathways and mechanisms involved in senescence and inflammaging coincide with those associated with cancer and other ARDs like osteoarthritis (OA). Thus, exploring these pathways using techniques like sequencing, identifying these factors and combatting them with the most suitable approach are crucial for healthy aging and the early detection of ARDs. Several approaches can be used to aid regeneration and reduce senescence in the bone. These may be pharmacological, non-pharmacological and lifestyle interventions. With increasing evidence towards the intricate relationship between aging, senescence, inflammation and ARDs, these approaches may also be used as anti-aging strategies for the aging bone marrow (BM).

Prevalence and Causes of Diagnostic Errors in Hospitalized Patients Under Investigation for COVID-19.

BACKGROUND: The COVID-19 pandemic required clinicians to care for a disease with evolving characteristics while also adhering to care changes (e.g., physical distancing practices) that might lead to diagnostic errors (DEs). OBJECTIVE: To determine the frequency of DEs and their causes among patients hospitalized under investigation (PUI) for COVID-19. DESIGN: Retrospective cohort. SETTING: Eight medical centers affiliated with the Hospital Medicine ReEngineering Network (HOMERuN). TARGET POPULATION: Adults hospitalized under investigation (PUI) for COVID-19 infection between February and July 2020. MEASUREMENTS: We randomly selected up to 8 cases per site per month for review, with each case reviewed by two clinicians to determine whether a DE (defined as a missed or delayed diagnosis) occurred, and whether any diagnostic process faults took place. We used bivariable statistics to compare patients with and without DE and multivariable models to determine which process faults or patient factors were associated with DEs. RESULTS: Two hundred and fifty-seven patient charts underwent review, of which 36 (14%) had a diagnostic error. Patients with and without DE were statistically similar in terms of socioeconomic factors, comorbidities, risk factors for COVID-19, and COVID-19 test turnaround time and eventual positivity. Most common diagnostic process faults contributing to DE were problems with clinical assessment, testing choices, history taking, and physical examination (all p < 0.01). Diagnostic process faults associated with policies and procedures related to COVID-19 were not associated with DE risk. Fourteen patients (35.9% of patients with errors and 5.4% overall) suffered harm or death due to diagnostic error. LIMITATIONS: Results are limited by available documentation and do not capture communication between providers and patients. CONCLUSION: Among PUI patients, DEs were common and not associated with pandemic-related care changes, suggesting the importance of more general diagnostic process gaps in error propagation.

Role of two-dimensional strain echocardiographic parameters in suspected acute coronary syndrome patients with initial non-diagnostic electrocardiogram and troponins: An observational study.

INTRODUCTION: Diagnosis of acute coronary syndrome (ACS) is often challenging especially in presence of initial normal troponins and non-specific electrocardiogram. The index study aimed at determining the diagnostic value of strain echocardiography in patients with suspected ACS but with non-diagnostic electrocardiogram and echocardiography findings. METHODS: The study was conducted on 42 patients with suspected ACS and non-diagnostic electrocardiograms, normal quantitative troponin-T levels, and left ventricular function. All patients underwent conventional and 2D-strain echocardiography followed by coronary angiography, within 24 h of admission. Patients with regional wall motion abnormalities (RWMA), valvular heart disease, suspected myocarditis, and past coronary artery disease (CAD) were excluded. RESULTS: Amongst the global strains, the global circumferential strain (GCS) was significantly reduced (p = .014) amongst those with significant CAD on angiography as opposed to global longitudinal strain (GLS) which was similar in the two groups (p = .33). The GCS/GLS ratio was also significantly reduced in patients with significant CAD compared to those with normal/mild disease on coronary angiography (p = .025). Both the parameters had good accuracy in predicting significant CAD. GCS displayed a sensitivity of 80% and a specificity of 86% at an optimal cut-off 31.5% (AUROC: .93, 95% CI: .601-1.000; p = .03), and likewise GCS/GLS ratio had a sensitivity of 80% and a specificity and 86% at a cut-off of 1.89% (AUROC: .86, 95% CI: .592-1.000; p = .049). GLS and peak atrial longitudinal strain (PALS) did not differ significantly in patients with/without significant CAD (p = .32 and .58, respectively). CONCLUSION: GCS and GCS/GLS ratio provides incremental value in comparison to GLS, PALS, and tissue Doppler indices (E/e') in patients with suspected ACS and non-diagnostic electrocardiogram and troponins. GCS at cut-off of >31.5% and GCS/GLS ratio >1.89 can reliably exclude patients with significant CAD in this setting.

Metabolic syndrome in non-obese patients with OSA: learning points of a cross-sectional study from a tertiary care hospital in Central India.

STUDY OBJECTIVES: Obesity is often considered mandatory for the diagnosis of Metabolic Syndrome (MS). Data on the prevalence of MS in non-obese patients with Obstructive Sleep Apnea (OSA) is scarce. This study was aimed to determine the prevalence of MS in non-obese patients with OSA. METHODOLOGY: All consecutively diagnosed patients with OSA between October 2018 and November 2019 were screened for metabolic syndrome. Patients with OSA and BMI < 25 kg/m2 (NOOSA) vs BMI > 25 kg/m2 (obese OSA) were compared. Lean waist NOOSA was defined as BMI < 25 kg/m2 and WC < 80 cm (32 in.) for women or < 90 cm (36 in.) for men. RESULTS: During the study period, 502 patients were diagnosed with OSA. MS was observed in 35% of patients with NOOSA compared to obese patients with OSA (79%). In the NOOSA group, hypertension, impaired fasting glucose, diabetes mellitus and dyslipidemia were observed in 65, 48, 14 and 61% respectively and all of these parameters were significantly more common in the obese group (p < 0.001). Parameters of OSA severity (apnea-hypopnea index or AHI, time spent below 90% saturated or T90, and nadir oxygen) were significantly more severe in the obese group with OSA. Approximately 83% of patients in the NOOSA group had at least two metabolic risk factors, compared to the obese OSA group, in which 95% had two or more metabolic risk factors. Sixty-four percent of patients with NOOSA with lean waist had at least two metabolic risk factors. At BMI cut-offs of < 25, < 27 and < 30 kg/m2; 35, 46 and 57% of patients with OSA respectively had metabolic syndrome. CONCLUSION: Metabolic syndrome was observed in approximately one in three patients with OSA and BMI < 25 kg/m2. Approximately two of every three lean waist non-obese patients with OSA had at least two markers of metabolic syndrome. The role of OSA in the development of metabolic syndrome in non-obese individuals needs further exploration.

Changing Critical Care Patterns and Associated Outcomes in Mechanically Ventilated Severe COVID-19 Patients in Different Time Periods: An Explanatory Study from Central India.

Background: The outcomes in critical illness depend on disease severity, practice protocols, workload, and access to care. This study investigates the factors affecting outcomes in mechanically ventilated coronavirus disease-2019 acute respiratory distress syndrome (COVID-19 ARDS) patients admitted in a tertiary teaching hospital intensive care unit (ICU) in Central India with reference to different time periods in pandemic. This is one of the largest series of mechanically ventilated COVID-19 ARDS patients, globally. Methods: This retrospective cohort study classified the entire data into four time periods (Period 1: April 2020 to June 2020; Period 2: July 2020 to September 2020; Period 3: October 2020 to December 2020; and Period 4: January 2021 to April 2021). We performed a multivariable-adjusted analysis to evaluate predictors of mortality, adjusted for baseline-severity, sequential organ failure assessment (SOFA score) and time period. We applied mixed-effect binomial logistic regression to model fixed-effect variables with incremental complexity. Results: Among the 56 survivors (19.4%) out of 288 mechanically ventilated patients, there was an up-gradient of survival proportion (0, 18.2, 17.4, and 28.6%) in four time periods. Symptom-intubation interval (OR 1.16; 95% CI 1.03-1.31) and driving pressures (DPs) (OR 1.17; 95% CI 1.07-1.28) were significant predictors of mortality in the model having minimal AIC and BIC values. Patients aged above 60 years also had a larger effect, but statistically insignificant effect favoring mortality (OR 1.99; 95% CI 0.92-4.27). The most complex but less parsimonious model (with higher AIC/BIC) indicated the protective odds of high steroid on mortality (OR 0.59; 95% CI 0.59-0.82). Conclusion: The outcomes in mechanically ventilated COVID-19 ARDS patients are heterogeneous across time windows and may be affected by the complex interaction of baseline risk and critical care parameters. How to cite this article: Saigal S, Joshi A, Panda R, Goyal A, Kodamanchili S, Anand A, et al. Changing Critical Care Patterns and Associated Outcomes in Mechanically Ventilated Severe COVID-19 Patients in Different Time Periods: An Explanatory Study from Central India. Indian J Crit Care Med 2022;26(9):1022-1030.

Successful use of tPA for thrombolysis in COVID related ARDS: a case series.

We describe successful usage of low dose Tissue plasminogen activator (tPA) (30-50 mg) in three COVID19 critically ill patients, who were in worsening respiratory failure in-spite of being on therapeutic anticoagulation. All patients had respiratory rate > 40; FiO2 > 0.7(on NIV); PiO2/FiO2 ratio < 100 and D-dimer>1000 ng/ml. C.T. Pulmonary Angiography could not be done in these patients due to poor general condition, but 2D echo was normal and none of the patients was in shock. So there was no conventional indication of thrombolysis in these patients, yet after thrombolysis, we saw dramatic changes in oxygenation. All patients became off oxygen within 3-7 days and were discharged within 2 weeks. The whole idea was to prevent intubation, since mortality rates are very high in intubated COVID19 patients. tPA is associated with <1% risk of fatal bleed. In this unprecedented pandemic with high mortality rates, thrombolysis could be an effective and safe option in carefully selected critically ill patients of COVID19.

Combination of positional therapy with positive airway pressure for titration in patients with difficult to treat obstructive sleep apnea.

INTRODUCTION: Positional therapy has been described as add-on therapy to a mandibular advancement device, but the efficacy of combination of positional therapy and positive airway pressure (PPAP) has not been documented. We have found PPAP therapy as an effective method of titration in patients with difficult to treat OSA (obstructive sleep apnea). METHODOLOGY: This retrospective analysis was done in patients who had difficult to treat OSA, i.e., in whom titration in the supine position was unacceptable with any PAP device (CPAP or bilevel PAP) and could only be successfully titrated with a PAP device in the lateral position. This study describes our experience of PPAP therapy. Baseline characteristics and polysomnography data of patients who were successfully titrated in supine v/s lateral positions were compared. RESULTS: Of 272 consecutive patients with OSA selected for analysis, 218 patients (191 and 27 with CPAP and bilevel PAP, respectively) could be successfully titrated in supine position. Further 54 (20%) patients in whom titration in supine position was unacceptable were titrated in lateral position. Patients titrated with PAP in the lateral position therapy group had higher BMI, higher neck and waist circumference, and lower awake sPO2 and nadir sPO2 during sleep, and spent more time in sleep with sPO2 < 90%. CONCLUSION: Combination of positional therapy and PAP device is an effective way of titration for difficult to treat OSA patients. It can be tried in patients who fail titration in supine position.

Admission Serum Chloride Levels as Predictor of Stay Duration in Acute Decompensated Heart Failure.

OBJECTIVE: Recent studies have shown that lower serum chloride is associated with diuretic resistance and increased mortality in heart failure. Impact of lower admission chloride on duration of stay in acute decompensated heart failure (ADHF) has not been studied previously. METHODS: In this retrospective analysis, we studied the effect of admission serum chloride on the duration of hospital stay in patients admitted with ADHF. A total of 167 patients were studied. Serum chloride levels were divided into tertiles - <96 meq/L (tertile 1), 96-101 meq/L (tertile 2), and >101 meq/L (tertile 3) based on the distribution of serum chloride levels in our patients. RESULTS: The median lengths of hospital stay in tertiles 1, 2, and 3 were 8(Interquartile range :6 -11), 7 (Interquartile range :5 -10.50), and 6 days(Interquartile range :4.25 - 8), respectively (p = 0.011). Admission serum chloride levels were inversely associated with duration of stay (R2 linear = 0.074, p = 0.001). On multiple linear regression analysis, serum chloride remained independent predictor of increased hospital stay (p=0.003) while association with serum sodium was not significant (p=0.07). 1 unit increase in chloride level was associated with 1.3% (p=0.003) decrease in hospital stay (95% CI: 2.2% to 0.5%). CONCLUSION: This retrospective analysis suggests that admission serum chloride levels are independently and inversely associated with increased duration of stay. This is independent of admission sodium levels. Thus serum chloride, rather than sodium, is an important poor prognostic marker in heart failure patients.

Changing pattern of secondary cancers among patients with malignant thymoma in the USA.

BACKGROUND: The risk of developing secondary cancers (SCs) among patients with malignant thymoma in the US has not been estimated in the more recent time period. Methods: We extracted demographic and treatment data from the SEER database to estimate the standardized incidence ratios (SIRs). Results: Of 1570 patients with thymoma 211 (13.4%) had SCs. The overall risk of developing SCs was higher among patients with thymoma (SIR: 1.54, 95% CI: 1.34-1.76). The SIRs for cancers of lung, esophagus, sigmoid colon, soft tissue and heart, kidney, NHL and leukemia was significantly higher as compared to the general US population. Conclusions: Patients with thymoma are at modestly elevated risk of developing SCs as compared to the general US population. Although the overall risk has not changed after 14 additional years of follow up, the distribution of SCs has significantly broadened, with increased diversity across type and anatomic location of SCs.

Global Level of Plasma DNA Methylation is Associated with Overall Survival in Patients with Hepatocellular Carcinoma.

BACKGROUND: The impact of folate deficiency on global DNA methylation is uncertain. It also is unclear whether global DNA methylation is associated with outcome in HCC. LINE-1 methylation levels, as a surrogate marker of global methylation, may be influenced by folate deficiency. However, the interaction between LINE-1 methylation and folate level on overall survival (OS) in hepatocellular carcinoma (HCC) patients is unknown. We evaluated whether LINE-1 hypomethylation and folate deficiency are associated with HCC prognosis. METHODS: We prospectively recruited 172 HCC patients between 2008 and 2012. LINE-1 methylation levels in plasma and white blood cells (WBC) were measured by pyrosequencing, and plasma folate levels by a radioprotein-binding assay. RESULTS: Patients with plasma LINE-1 methylation <70.0% (hypomethylation) had significantly worse OS compared with those with ≥70.0% methylation (hypermethylation) [hazard ratio (HR) = 1.77; 95% confidence interval (CI) 1.12-2.79; P = 0.015]. HCC patients with lower plasma folate levels also had worse survival (<27.7 vs. ≥27.7 nmol/L; HR = 1.96; 95% CI, 1.24-3.09; P = 0.004). Furthermore, survival was poor in patients in whom both plasma LINE-1 methylation and folate levels were low compared with those patients in whom both levels were high (HR = 3.36; 95%CI, 1.77-6.40; P < 0.001). This interaction neared statistical significance (P = 0.057). No significant association was found between WBC LINE-1 methylation levels and survival. CONCLUSIONS: These findings suggest that both lower plasma levels of LINE-1 methylation and folate are associated with worse survival in HCC patients.

Age at cancer diagnosis, amenability to medical interventions, and racial/ethnic disparities in cancer mortality.

PURPOSE: Racial disparities in cancer mortality may be greater for cancers that are amenable to available early detection and treatment (amenability level). We investigated whether these patterns vary by age at cancer diagnosis. METHODS: Using 5-year relative survival rates (5Y-RSR), we classified 51 cancer sites into least amenable, partly amenable, and mostly amenable cancers (<40%, 40-69%, ≥70% 5-YRS, respectively). We examined whether racial disparities in mortality rates (African-Americans, Asian/Pacific Islanders, Hispanics, whites), as estimated through Cox regression models, were modified by age at diagnosis and amenability level in 516,939 cancer cases diagnosed in 1995-1999. RESULTS: As compared with whites, all racial minority groups experienced higher cancer mortality rates in the youngest age group of 20-34 years. African-Americans and Hispanics diagnosed with partly and mostly amenable cancers had higher mortality rates relative to whites with cancers of the same amenability levels; further, these differences decreased in magnitude or reversed in direction with increasing age. In contrast, the racial differences in mortality were smaller and remained fairly constant across age groups for least amenable cancers. For example, in the youngest (20-34) and oldest (80-99) age groups, the adjusted hazard ratios (HRs) for African-Americans versus whites with least amenable cancers were, respectively, 1.26 (95% CI 1.02, 1.55) and 0.90 (95% CI 0.85, 0.96), while the HRs for African-Americans versus whites with mostly amenable cancers were 2.77 (95% CI 2.38, 3.22) and 1.07 (95% CI 0.98, 1.17). CONCLUSIONS: Cancer survival disadvantage for racial minorities is larger in younger age groups for cancers that are more amenable to medical interventions.

Serum adiponectin is associated with worsened overall survival in a prospective cohort of hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The rise in metabolic syndrome has contributed to this trend. Adipokines, such as adiponectin, are associated with prognosis in several cancers, but have not been well studied in HCC. METHODS: We prospectively enrolled 140 patients with newly diagnosed or recurrent HCC with Child-Pugh (CP) class A or B cirrhosis. We examined associations between serum adipokines, clinicopathological features of HCC, and time to death. We also examined a subset of tumors with available pathology for tissue adiponectin receptor (AR) expression by immunohistochemistry. RESULTS: The median age of subjects was 62 years; 79% were men, 59% had underlying hepatitis C, and 36% were diabetic. Adiponectin remained a significant predictor of time to death (hazard ratio 1.90; 95% confidence interval 1.05-3.45; p = 0.03) in a multivariable adjusted model that included age, alcohol history, CP class, stage, and serum α-fetoprotein level. Cytoplasmic AR expression (AR1 and AR2) in tumors trended higher in those with higher serum adiponectin levels and in those with diabetes mellitus, but the association was not statistically significant. CONCLUSIONS: In this hypothesis-generating study, we found the serum adiponectin level to be an independent predictor of overall survival in a diverse cohort of HCC patients. IMPACT: Understanding how adipokines affect the HCC outcome may help develop novel treatment and prevention strategies.

Cytological Perspective in a Case of Doege-Potter Syndrome With Hypoinsulinemic Hypoglycemia.

Solitary fibrous tumor (SFT) of the lung is a rare mesenchymal neoplasm of uncertain histogenesis, unknown molecular features, and unpredictable clinical behavior, characterized by NAB2-STAT6 fusion. Hypoglycemia accompanying SFT (Doege-Potter syndrome) is an uncommon presentation. We present the cytomorphological features on biopsy imprint smears of a histopathologically confirmed case of SFT of the lung with an uncommon presentation. A 76-year-old non-smoker, non-alcoholic, and non-diabetic man presented with complaints of intermittent episodes of confusion with syncopal attacks (>10 episodes) for six months. The patient had no respiratory complaints and no history of weight loss. Laboratory investigations revealed fasting blood sugar of 38 mg/dl with low serum insulin and C-peptide levels. Physical examination revealed reduced air entry on the left side of the chest. Chest X-ray showed left-sided homogenous opacity. High-resolution computed tomography (HRCT) of the chest showed a large left-sided lung mass. A biopsy was performed. Biopsy imprint smears were cellular and showed tumor cells arranged in clusters and fragments with traversing capillaries displaying monomorphic pump to oval nuclei, fine granular evenly dispersed chromatin, regular nuclear membrane, inconspicuous nucleoli, and a moderate amount of wispy cytoplasm. Foci of intercellular hyaline stromal material were noted. A cytodiagnosis of low-grade mesenchymal neoplasm was made. Histopathology revealed a cellular tumor comprising tightly packed round to fusiform cells arranged around blood vessels with intervening thick collagen, positive for CD99, vimentin, BCL2, CD34, and STAT6 and negative for EMA, CK AE1/AE3, S100, TLE1, and SMA. Familiarity with cytomorphology plays a pivotal role in clinching an early diagnosis of this rare neoplasm of the lung, particularly in the setting of presentation with hypoglycemia.

Effect of pulmonary rehabilitation in patients with post-tuberculosis sequelae with functional limitation.

BACKGROUND: Pulmonary rehabilitation improves dyspnea, functional limitation and quality of life in patients with chronic respiratory disease especially Chronic obstructive pulmonary disease (COPD). Whether Pulmonary rehabilitation (PR) will have similar effect in patients with post-tuberculosis sequelae or not and whether the two morphological variants will respond similarly or not was the purpose of our study. METHODS: Adult patients fulfilling the inclusion criteria of a diagnosis of post-tuberculosis sequelae with functional limitation (modified medical research council [mMRC] grade 1 or more) were recruited over a period of two years. A baseline health assessment in the different domains of health was done at the beginning and repeated just after the completion of the rehabilitation program at 6 weeks. RESULTS: 26 patients completed the PR protocol of our study. Dyspnea improved from an mMRC grade of 1.5 to 0.7 post-PR (p < 0.001). 6MWD increased by 34 meters from a baseline value of 408.6 meters to 442.7 meters post-PR. (p-value 0.3) St. George's Respiratory Questionnaire (SGRQ) symptom score decreased by 13 points, SGRQ activity score decreased by 18 points, SGRQ impact score decreased by 18 and SGRQ total score decreased by 17 points with p-values of 0.037, 0.002, 0.004 and 0.002 for SGRQ symptom score, SGRQ activity score, SGRQ impact score, SGRQ total score respectively. Depression Anxiety Stress Scale (DASS) Stress score decreased by 6.7, DASS Anxiety score decreased by 6.6, and DASS Depression score decreased by 5.5 points. Intergroup comparison revealed both bronchiectasis predominant group and fibrosis predominant group responded similarly to PR. CONCLUSION: PR improved parameters assessing dyspnea, quality of life and mental health indices significantly. Improvement in functional capacity was not statically significant. Both the morphological variants responded similarly to the PR.

Sex-specific differences in presenting symptoms of obstructive sleep apnea.

OBJECTIVES: Scant data from India are available on the gender differences in presenting features of Obstructive Sleep Apnea (OSA) in India. This study aims to compare male and female patients with OSA for general characteristics and presenting symptoms. METHODOLOGY: Retrospective study was done in OSA patients diagnosed in our sleep lab. History, biochemical reports, and polysomnography variables were retrieved from the sleep registry and were compared between males and females. RESULTS: Out of 514 patients of OSA (367 males; 147 females). Females were older (55.97 ± 9.73 v/s 50.2 + 12.70 years, P<0.001) and more obese (BMI 35.26 ± 7.17 v/s 29.58 ± 5.49 Kg/m2; P<0.001). Waist and hip circumference were significantly higher in the female patients (P = 0.009 and <0.001 respectively). Morning headache, nocturia, fatigability (P < 0.001), and depression (P = 0.005) was more common in females (P = 0.036). Hypersomnia was more commonly seen in males (P < 0.001). Mean diastolic blood pressure was significantly higher in males, although no difference was seen in Systolic BP. Females had higher mean Fasting Blood glucose (FBS) (P = 0.02). Apnea hypopnea index was significantly higher in females {P = 0.01}. CONCLUSION: Women with OSA are more obese, elderly, and with higher fasting blood glucose than males at the time of diagnosis. Females have a higher prevalence of symptoms like fatigability, depression, nocturia and early morning headache and had more severe AHI than males.

Cytohistological findings and diagnostic challenges in rare pediatric pulmonary mesenchymal malignancies: A report of two cases.

Pulmonary mesenchymal tumors are uncommon neoplasms and the data available on their clinical, cytohistomorphological, immunohistochemical, and molecular findings are limited, leading to difficulty in timely diagnosis and management. Case 1: A 12-year-old boy presented with a right endobronchial mass. Imprint smears from endobronchial biopsy revealed moderately pleomorphic spindle cell tumor arranged in fascicles and perivascular pattern with attached myxoid material showing occasional mitotic activity suggesting a cytological diagnosis of sarcoma. Biopsy also displayed similar morphology. Extensive immunohistochemistry (IHC) showed diffuse SMA, focal AE1/AE3, and diffuse ALK positivity along with a MIB/Ki67 index of 30%-40% leading to the diagnosis of inflammatory myofibroblastic tumor (IMT; Sarcoma grade). Case 2: A 8-year-old boy presented with a huge left-sided mass replacing the entire lung parenchyma and eroding adjoining ribs. Pleural fluid cytology revealed vague clusters of PAS-positive diastase-sensitive small atypical cells with associated inflammatory cells in the hemorrhagic background, suggesting a diagnosis of malignant small round blue cell tumor. Trucut biopsy from the mass showed spindled to round cells showing diffuse positivity with CD99 and BCL-2. Molecular studies with reverse transcription-PCR (RT-PCR) for SYT-SSX and EWS-FLI1 were negative for synovial sarcoma and Ewing's sarcoma, respectively. Given the clinical setting, PAS positivity, IHC, and molecular studies, the diagnosis of tumors of uncertain differentiation with the possibility of Ewing's sarcoma family of tumors (ESFT) with a translocation between EWS1 and other ETS-family members (ERG, FEV, ETV1, E1AF, etc.) was suggested.

Effect of digital tools to promote hospital quality and safety on adverse events after discharge.

OBJECTIVES: Post-discharge adverse events (AEs) are common and heralded by new and worsening symptoms (NWS). We evaluated the effect of electronic health record (EHR)-integrated digital tools designed to promote quality and safety in hospitalized patients on NWS and AEs after discharge. MATERIALS AND METHODS: Adult general medicine patients at a community hospital were enrolled. We implemented a dashboard which clinicians used to assess safety risks during interdisciplinary rounds. Post-implementation patients were randomized to complete a discharge checklist whose responses were incorporated into the dashboard. Outcomes were assessed using EHR review and 30-day call data adjudicated by 2 clinicians and analyzed using Poisson regression. We conducted comparisons of each exposure on post-discharge outcomes and used selected variables and NWS as independent predictors to model post-discharge AEs using multivariable logistic regression. RESULTS: A total of 260 patients (122 pre, 71 post [dashboard], 67 post [dashboard plus discharge checklist]) enrolled. The adjusted incidence rate ratios (aIRR) for NWS and AEs were unchanged in the post- compared to pre-implementation period. For patient-reported NWS, aIRR was non-significantly higher for dashboard plus discharge checklist compared to dashboard participants (1.23 [0.97,1.56], P = .08). For post-implementation patients with an AE, aIRR for duration of injury (>1 week) was significantly lower for dashboard plus discharge checklist compared to dashboard participants (0 [0,0.53], P < .01). In multivariable models, certain patient-reported NWS were associated with AEs (3.76 [1.89,7.82], P < .01). DISCUSSION: While significant reductions in post-discharge AEs were not observed, checklist participants experiencing a post-discharge AE were more likely to report NWS and had a shorter duration of injury. CONCLUSION: Interventions designed to prompt patients to report NWS may facilitate earlier detection of AEs after discharge. CLINICALTRIALS.GOV: NCT05232656.

Should topiramate be initial therapy in the management of idiopathic intracranial hypertension?: A literature review.

Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology that primarily affects obese women of childbearing age. Symptoms include disabling headaches, visual disturbances, and intracranial noises (pulsatile tinnitus). Currently, no standardized treatment guidelines are available and the current management focuses on weight loss and acetazolamide use. There is an increasing body of evidence suggesting that the initial use of topiramate may be considered in IIH treatment. Acetazolamide is the recommended initial treatment for IIH, with topiramate often used as a second-line agent. Topiramate has multiple benefits to indicate it would pose effective in IIH management. Through varying mechanisms, it leads to weight loss and improves migraine headache control, the most common headache phenotype in IIH. Topiramate also inhibits the carbonic anhydrase enzyme like acetazolamide to reduce intracranial pressure and treat papilledema. The safety profile of topiramate is comparable or superior to acetazolamide. To date, there are limited studies comparing topiramate to acetazolamide or other treatment modalities in IIH. Based on its varying mechanisms of action, topiramate is a strong potential treatment agent for IIH, yet acetazolamide is often chosen first-line. However, the data supporting use of acetazolamide or topiramate is inefficient to designate one agent preferred over the other. There is a need for further studies assessing topiramate use in the treatment of IIH, and comparing topiramate use to other treatment modalities.