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).

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.

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.

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.

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.

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.

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.

Clinical profile and outcome of cardiac manifestations in patients presenting with multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection.

Multisystem inflammatory syndrome in children (MIS-C) can cause significant morbidity and mortality in children. This study was conducted to assess the pattern and outcome of cardiac abnormalities in MIS-C. This retrospective study was conducted in children with MIS-C between 1 month and 18 years. We enrolled 53 children with a mean age of 7.78 ± 4.62 years. Overall, 35.8% of children with MIS-C had cardiac manifestations in the form of coronary artery abnormalities (CAAs) or left ventricular (LV) dysfunction. Younger age (P 0.009) and high C-reactive protein at admission (P = 0.001) were significant predictors of cardiac involvement. CAAs were seen in 11.3% of children. On follow-up, 67% and 83% of children showed regression of CAA at 1 and 6 months, respectively. 24.5% of patients had presented with LV dysfunction. LV ejection fraction improved significantly at 1 month (P = 0.002) and 6 months (P = 0.001). Cardiac outcomes in MIS-C were favorable with timely identification and treatment.

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.

Bronchoalveolar Lavage in Diagnostic Evaluation of Pulmonary Diseases- An Institutional Experience.

Background: Bronchoalveolar lavage (BAL) is a widely accepted investigative tool for the diagnosis of pulmonary lesions. This study was done to find out the usefulness of BAL in diagnosis of pulmonary lesions from central Indian patient population. Methods: A cross-sectional prospective study was performed over a period of three years. All the BAL specimens of patients presenting to Department of Pulmonary Medicine and Tuberculosis during a period of January 2017 to December 2019 were included in the study. Cyto-histopathologic correlation was done, wherever available. Results: Of total 277 cases, there were 178 (64.5%) males and 99 (35.5%) females. The age of patients ranged from 4 years to 82 years. In 92 (33%) cases, specific infective etiology could be identified on BAL cytology, the most common being tuberculosis (26%) followed by fungal infections (2%). Rarely, infections like nocardia, actinomycosis, and hydatidosis were also identified. Eight cases (3%) of malignancy were identified which included two cases of adenocarcinoma, one case of small cell carcinoma, three cases of poorly differentiated carcinoma, and two cases suspicious for malignancy. Some rare diagnoses like diffuse alveolar damage, pulmonary alveolar microlithiasis, and pulmonary alveolar proteinosis could be identified on BAL. Conclusion: BAL is useful in primary diagnosis of infections and malignancies of lower respiratory tract. BAL may aid in diagnostic workup of diffuse lung diseases. A combination of clinical information, high-resolution computed tomography, and BAL analysis may furnish an assured diagnosis to the clinician and obviate need for invasive procedures.

Ampreloxetine Versus Droxidopa in Neurogenic Orthostatic Hypotension: A Comparative Review.

Neurogenic orthostatic hypotension (nOH) is a disabling problem of autonomic dysfunction in patients with Parkinson's disease, which is associated with poor quality of life and higher mortality rates. The purpose of this literature review was to explore and compare the efficacy and safety of droxidopa (an existing treatment) and ampreloxetine (a newer medication) in the treatment of nOH. We used a mixed-method literature review that addresses the epidemiology, pathophysiology, and pharmacological and non-pharmacological management of nOH in Parkinson's disease in a general way, with a more exploratory approach to droxidopa- and ampreloxetine-controlled trial studies. We included a total of 10 studies of randomized controlled trials with eight studies focused on droxidopa and two studies focused on ampreloxetine. These two drugs were analyzed and compared based on the collected individual study results. Treatment of nOH in Parkinson's disease patients with droxidopa or ampreloxetine showed clinically meaningful and statistically significant improvements relative to placebo on the components of the OHSA (Orthostatic Hypotension Symptom Assessment) composite score and OHDAS (Orthostatic Hypotension Daily Activity Scale composite scores) composite score. Droxidopa had an improved effect on daily activities, with an associated increase in standing systolic blood pressure (BP), but the long-term efficacy of droxidopa has not been documented. Standing systolic BP was maintained by ampreloxetine and worsened after the withdrawal phase. This highlights the importance of conducting further research which will help us to improve the therapeutic approach for patients with nOH and Parkinson's disease.

Obstructive sleep apnea and ambulatory blood pressure abnormalities in children with chronic kidney disease.

BACKGROUND: Obstructive sleep apnea (OSA) and hypertension are common complications in children with chronic kidney disease (CKD). Progression of CKD can aggravate OSA and hypertension whereas worsening sleep apnea can make hypertension difficult to treat in CKD patients. We, therefore, conducted a prospective study to evaluate the association between OSA and hypertension in pediatric patients with CKD. METHOD: In this prospective observational study consecutive children with CKD stage 3-5 (nondialysis dependent) underwent overnight polysomnography and 24-h ambulatory blood pressure monitoring (ABPM). The detailed clinical features and investigations were recorded in a prestructured performa. RESULTS: Twenty-two children completed overnight polysomnography and 24-h ABPM was performed within 48 h of performing polysomnography. The median (IQR) age of the study population was 11 (8.5-15.5) years, with an age range of 5-18 years. Moderate-severe OSA defined as apnea-hypopnea index (AHI ≥5) was seen in 14 (63.6%) children, periodic limb movement syndrome in 20 (91%) and poor sleep efficacy in 9 (40.9%) children. Ambulatory blood pressure was abnormal in 15 (68.2%) children with CKD. Of them, 4 (18.2%) had ambulatory hypertension, 9 (40.9%) had severe ambulatory hypertension and 2 (9.1%) had masked hypertension. A statistically significant correlation of sleep efficiency with nighttime DBP SD score/Z score (SDS/Z) (r = -0.47; P = 0.02); estimated glomerular filtration rate with SBP loads (r = -0.61; P < 0.012); DBP loads (r = -0.63; P < ) and BMI with SBP load (r = 0.46; P = 0.012) was found. CONCLUSION: Our preliminary findings suggest that ambulatory blood pressure abnormalities, OSA, periodic limb movement syndrome and poor sleep efficiency are highly prevalent in children with CKD stages 3-5.

Quantum of Stress Hyperglycemia at the Time of Initial Diagnosis of Tuberculosis.

Background India has a high burden of both tuberculosis (TB) and diabetes mellitus (DM). The National TB Elimination Program recommends testing for glycemic status at the initiation of therapy; however, some individuals with elevated sugar levels might have stress hyperglycemia (SH) instead of true DM. Our aim was to perform a longitudinal glycemic assessment of individuals with TB to identify those with true newly diagnosed DM and those with SH. Methods We identified newly diagnosed adults with TB and abstracted information about demography, co-morbidities, disease severity, and glucose-lowering agents. A glycemic assessment was performed at baseline and at the end of six months. Results We included 150 patients with TB, and based on their initial HbA1c values, 82 (54.6%, 95% CI: 46-62%) had dysglycemia (30% had HbA1c levels above 6.4% and 24.6% had values between 5.9% and 6.4%) and 31 (20.7%, 95% CI: 14-18%) had SH. Among individuals with both baseline and follow-up glycemic values, 30% of the individuals previously defined as DM were characterized as SH. The proportion of true SH was 43% (95% CI: 33-60%). Conclusion Most individuals who have dysglycemia at the time of their TB diagnosis have SH. A close follow-up of such individuals will identify those who really require long-term glucose-lowering therapy.

Corrigendum: Genotypic variation in Na, K and their ratio in 45 commercial cultivars of Indian tropical onion: A pressing need to reduce hypertension among the population.

[This corrects the article DOI: 10.3389/fnut.2023.1098320.].

Prevalence and predictors of lower extremity atherosclerotic disease amongst high-risk patients using ankle brachial index.

INTRODUCTION: The prevalence of lower extremity artery disease (LEAD) continues to increase worldwide. This is expected to translate into logarithmic rise in lower-limb amputations especially in the developing world. Majority of patients suffering from LEAD remain asymptomatic until late and are vulnerable to limb-threatening complications unless actively screened and treated. METHODS: This was a prospective, single-center, observational study to determine the prevalence and predictors of LEAD. Patients with known atherosclerotic vascular disease (but not known LEAD) or those at risk were enrolled. All underwent ankle brachial index (ABI) measurement as per the standard protocol. A threshold of ABI ≤0.90 was taken to diagnose LEAD. RESULTS: A total of 1000 patients were enrolled. The mean age of the group was 61.4 ± 10.0 years and the prevalence of LEAD was 10.2%. Amongst those who had LEAD, the majority of patients (69.6%) had no symptoms. The prevalence of LEAD in diabetic population in our study was 13.2% and it was 30.9% in coronary artery disease patients . Factors independently linked to LEAD on regression analysis included advanced age, presence of diabetes, smoking history, lower serum HDL and a lower ejection fraction. CONCLUSIONS: The vast majority of patients suffering from LEAD are asymptomatic. Early diagnoses and institution of appropriate medical and physical therapy can prevent excess morbidity and mortality due to LEAD. Factors independently linked to LEAD are advanced age, presence of diabetes, smoking history, lower serum HDL and a lower ejection fraction. The presence of either of these should signal undertaking of appropriate steps to unmask underlying LEAD.

Genotypic variation in Na, K and their ratio in 45 commercial cultivars of Indian tropical onion: A pressing need to reduce hypertension among the population.

The intake of diets with higher sodium (Na) and lower potassium (K) has been considered a leading factor for the development of hypertension (HTN). Majority of junk, processed and packaged food have higher Na contents. To counter the effects of diet on HTN, the identification of high K/Na ratio plant-based food is needed. Among fruits and vegetables, onion could be the ideal option since it contains high K content. Keeping this in mind, 45 commercially well adapted short day Indian onion cultivars were evaluated for K and Na content and their ratio to isolate suitable cultivars to prevent HTN in the Indian population. The data suggested wide variation among the genotypes for K, Na, and K/Na ratio ranging from 490.2 ± 17.0 to 9160.0 ± 96.7 mg/kg on dry matter basis, 52.7 ± 3.0 to 458.2 ± 61.7 mg/kg on dry matter basis and 3.1 ± 0.7 to 109.5 ± 17.3, respectively. The K content was recorded as significantly highest in the yellow-coloured bulb variety "Arka Pitamber" (9160.1 ± 96.7) followed by Pusa Sona (7933.2 ± 292.8). On the other hand, minimal K was assessed in the white-coloured bulb variety "Agrifound White" (490.3 ± 17.0) followed by Udaipur Local (732.9 ± 93.4). Twelve cultivars exhibited > 7000 mg K content, while nine cultivars recorded < 1500 mg. On the contrary, Na was recorded as significantly highest in the dark-red-coloured bulbs and the lowest in white bulbs. Furthermore, it was determined that there was a more than 35-fold difference observed between the highest (109.5) and lowest (3.1) K/Na ratio in the bulbs of tested cultivars. Cluster analysis revealed three major groups comprising of 23, 13 and 9 genotypes. This information could form the base for public health, food and onion researchers to design suitable cultivars to prevent HTN as a population-wide approach. The next century is going to be food-based for the amelioration of human diseases in a sustainable way without any after-effects on the human body.

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.

Clinical profile of patients with cardiac amyloidosis in India.

Limited data exists on patients with cardiac amyloidosis (CA) in India, due to underdiagnosis and late presentation. We present single centre data from 13 patients over a 4 year period with a median age of 65 years. A majority presented with symptomatic heart failure (69%) and eight patients had confirmed AL amyloidosis. At the end of the follow up period, 46% patients died, with 30% of the overall cohort dead within six months. Among the survivors, 71% continue to have NYHA grade III/IV symptoms. A suggested algorithm for earlier diagnosis in resource constrained settings is also presented.