The need for insulin infusion therapy was associated with higher energy (p = 0.001) and glucose delivered through artificial nutrition (p = 0.040). Those patients with stress hyperglycemia showed higher ICU stays . Serum osteocalcin was a good marker for hyperglycemia, as it inversely correlated with glycemia at admission in the ICU  and at days 2  and 3 . In conclusion, hyperglycemia in critically ill COVID-19 patients was associated with longer ICU stays. Low circulating osteocalcin was a good marker for stress hyperglycemia.We aimed to study the possible association of stress hyperglycemia in COVID-19 critically ill patients with prognosis, artificial nutrition, circulating osteocalcin, and other serum markers of inflammation and compare them with non-COVID-19 patients. Fifty-two critical patients at the intensive care unit (ICU), 26 with COVID-19 and 26 non-COVID-19, were included. Glycemic control, delivery of artificial nutrition, serum osteocalcin, total and ICU stays, and mortality were recorded. Patients with COVID-19 had higher ICU stays, were on artificial nutrition for longer ( Hyperglycemia is a risk factor for a more severe course of the disease, as hospitalized COVID-19 patients with diabetes show longer hospital stays than patients without diabetes [Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic, which has affected more than two hundred million individuals and is the cause of more than four million deaths worldwide as of this writing —which is normally part of the nutritional therapy together with enteral nutrition (EN) in critically ill patients —might beIn the last few years, circulating osteocalcin, an osteoblast-specific protein, has shown extraskeletal metabolic activity, such as promoting insulin secretion and increasing peripheral insulin sensitivity . ReducedTherefore, given this previous knowledge, we aimed to study the possible association of stress hyperglycemia in COVID-19 critically ill patients with a worse prognosis compared to non-COVID-19 patients. We also aimed to explore the possible associations of hyperglycemia with circulating osteocalcin concentrations, the composition of artificial nutrition, and serum markers of inflammation.Fifty-two patients were included in this study: 26 consecutive patients with severe COVID-19 requiring admission to the ICU and 26 non-COVID-19 critically ill postsurgical patients. The latter were historical controls before the COVID-19 pandemic occurred and had the following procedures: 7 cardiovascular surgery, 12 renal/urological surgery, 6 pelvic surgery, and 1 surgery for traumatic hemothorax. Patients with COVID-19 were diagnosed by the presence of SARS-CoV-2 in respiratory specimens by real-time polymerase chain reaction (RT-PCR) in pharyngeal swabs. All COVID-19 patients were critically-ill and on mechanical ventilation. They received our standard treatment protocol, including low molecular-weight heparin, glucocorticoids, and tocilizumab. Non-COVID-19 patients were all complicated postsurgical ones in need of mechanical ventilation and vasoactive drugs. Patients under 18 y were excluded as well as those with active cancer, pregnancy, or with end-stage renal or liver disease before the diagnosis of COVID-19.Patients in both groups were categorized as with or without diabetes mellitus based on a previous diagnosis. Stress hyperglycemia was defined as a plasma glucose level of ≥140 mg/dl. Continuous insulin infusion  was started when blood glucose was ≥180 mg/dl and adjusted for a glycemic range of 140–179 mg/dl . CapillaThe type of composition of artificial nutrition administered to the included patients were recorded. PN was delivered through a central line as soon as the patient was hemodynamically stable. Individualized formulae or standardized commercial bags were prepared by the hospital pharmacy. We aimed at 20–25 kcal/Kg/day, with a proportion of 3–6 g/Kg/day for glucose, 1.0 g/Kg/day for amino-acids, and less than 1 g/Kg/day for lipids, with 7–10 g/day of essential fatty acids. Vitamins and trace elements were also added by the hospital pharmacy. For those patients with ICU stays above 7 days, and whenever possible, EN was started with a standard, fiber-free formulation and PN gradually tapered as EN was tolerated and increased.The study protocol was approved by the Institutional Ethics Committee of our center (study code 147/20) and performed according to the Declaration of Helsinki. Written or verbal informed consent was obtained from all patients.Serum concentrations of glucose and other biochemical variables were measured with an Architect c16000/i2000-analyzer  and HbA1c by high-performance liquid chromatography . Immunoanalysis was employed for the measurement of C-reactive protein (CRP), procalcitonin  and D-dimer , and interleukins 6 (IL-6) and 12 (IL-12) by enzyme-linked immunosorbent assay  at ICU admission. Serum osteocalcin was measured by electrochemiluminescence Cobas-e601 , with normal range of 15.0–45.0 µg/L also at ICU admission. The intra- and inter-assay coefficients of variation were below 10%.We used GRANMO 7.12  for samp2 test and Fisher’s exact test as appropriate. Unpaired t-tests or Mann–Whitney U tests were used to compare the central tendencies of the different groups as appropriate. Bivariate correlation was employed to study the association between two continuous variables using Pearson or Spearman’s tests as appropriate. Two-way ANOVA was employed to analyze the effect of both COVID-19 and stress hyperglycemia on the studied continuous prognostic variables and corrected χ2 test for categorical ones. Finally a multivariate linear regression analysis was also performed with a backwards strategy. Analyses were performed using SPSS 17 . p < 0.05 was considered statistically significant.Results are expressed as means ± SD unless otherwise stated. The Kolmogorov–Smirnov statistic was applied to continuous variables. Logarithmic or square root transformations were used as needed to ensure normal distribution of the variables. To compare discontinuous variables, we used the χOf the 52 initially included patients, the results of 49 patients were finally analyzed, as three patients with COVID-19 had undetectable levels of osteocalcin . PatientWe did not find a difference in glycemia at ICU admission in the proportion of patients with stress hyperglycemia or in mean glycemia at ICU. However, patients with COVID-19 more frequently needed insulin infusion therapy for glycemic control and showed lower osteocalcin concentrations. Patients with COVID-19 were also on artificial nutrition for longer (both PN and EN) and received higher energy per day than non-COVID-19 ones but with similar amounts of delivered glucose per day. Serum CRP and procalcitonin at ICU admission were similar in both groups .n = 3), pulmonary embolism (n = 1), and multiorgan failure after septic shock (n = 3). COVID-19 patients died as a result of respiratory distress syndrome (n = 6) and pulmonary embolism (n = 2). The possibility of stroke and or any other CNS complications as the cause of death could not be accurately assessed due to profound sedation in these patients  and at day 2 . Those patients with stress hyperglycemia showed higher ICU stays. As expected, those patients with longer ICU stays needed more days on artificial nutrition for both PN  and EN .Total hospital stay did not correlate with glucose control, but ICU stay correlated with glycemia at admission in ICU .Circulating osteocalcin was lower in patients with COVID-19 . It was r = −0.476, p = 0.001) and at days 2  and 3   or age , and their levels were similar in men and women .Circulating osteocalcin concentrations inversely correlated with glycemia at the day of admission in the ICU (= 0.049) . Osteocar = 0.245, p = 0.097), at day 2 , or 3 . Conversely, the amount of glucose delivered through PN was positively correlated with glycemia at the day of admission in the ICU . In addition, mean glucose and energy delivered through artificial nutrition correlated with mean glycemia during ICU stay  (The amount of energy delivered through PN did not correlate with glycemia at the day of admission in the ICU (ctively) .t = 3.709, p = 0.001) and glucose delivered through artificial nutrition .Those patients in need of insulin infusion therapy compared with those on subcutaneous insulin received higher energy  but not with CRP , procalcitonin , IL-6 , or D-dimer  (Glycemia at the day of admission in the ICU was positively correlated with IL-12 (= 0.312) .p > 0.05 for IL-12, CRP, procalcitonin, D-dimer, and IL-6).Patients with stress hyperglycemia had more similar inflammatory markers at ICU admission than those without it . The sam2 test for categorical ones. Separated data in four groups are shown in In order to correct for the effects of both the presence of COVID-19 and stress hyperglycemia in prognostic parameters and osteocalcin, we performed a two-way analysis of variance for continuous variables and corrected χICU stay was higher with both COVID-19 diagnosis and the presence of stress hyperglycemia, indicating these two were independent prognostic factors. Conversely total hospital stay and mortality were not associated with either COVID-19 diagnosis or the presence of stress hyperglycemia. Circulating osteocalcin was lower in both COVID-19 patients and with the presence of stress hyperglycemia, but CRP and procalcitonin showed no associations .Insulin infusion was more frequent for both COVID-19 diagnosis and the presence of stress hyperglycemia. The time on artificial nutrition, both on TPN and EN, was longer in those patients with COVID-19 and with stress hyperglycemia. The amount of energy and glucose delivered by artificial nutrition were also associated with both the presence of COVID-19 and stress hyperglycemia and with their interaction .p < 0.001) and the presence of stress hyperglycemia  were retained by the model . When osteocalcin was introduced as the dependent variable, both COVID-19 diagnosis  and the presence of stress hyperglycemia  were retained by the model .Finally, a multivariate linear regression analysis was also performed with a backwards strategy, introducing COVID-19 diagnosis, the presence of stress hyperglycemia, the need for insulin infusion, age, and sex as independent variables and ICU stay as the dependent variable. Both COVID-19 diagnosis  were the days on both TPN  and EN  and the need for insulin infusion .Another multivariate regression analysis model was performed as to take into account the artificial nutrition characteristics on ICU stay, which was introduced as the dependent variable. The independent variables in this model were the days on artificial nutrition, both TPN and EN, the amount of energy and glucose delivered by artificial nutrition, and the need for insulin infusion. The presence of COVID-19 and stress hyperglycemia could not be introduced in the model, as they showed collinearity with the variables of artificial nutrition. The variables retained by the model (RIn the present study, we have shown that hyperglycemia in critically ill COVID-19 patients was associated with longer ICU stays and higher amounts of glucose delivered through artificial nutrition. Low circulating osteocalcin was lower in COVID-19 patients, in those with stress hyperglycemia, and in those in need for insulin infusion therapy. Therefore, osteocalcin could be considered a useful marker for stress hyperglycemia and prognosis at ICU.Osteocalcin, while playing important roles in bone remodeling, also contributes to glucose metabolism by affecting both insulin secretion and insulin sensitivity . In vitrCirculating osteocalcin was reduced in patients with severe COVID-19, in accordance with a recent report in which 40 patients were compared with 57 non-COVID-19 controls in a cross-sectional design . We furtDiabetes mellitus has shown to be a risk factor for a worse prognosis in patients with COVID-19 ,21 as weAmong the factors that may influence the appearance of stress hyperglycemia in critically ill patients, the release of inflammatory mediators might be one of the physiopathological pathways. Inflammatory cytokines excessively produce glucose by the liver and insulin resistance at the peripheral tissues , and theThe amount or glucose delivered through artificial nutrition might be another associated factor with stress hyperglycemia. It has been shown that among the metabolic complications of parenteral nutrition, hyperglycemia is one of them, and this may be especially important in older individuals . TherefoHowever, there is still a paucity of data in critically ill COVID-19 patients regarding the recommendation of the type of artificial nutrition and also its composition. Our results showed that the amount of glucose delivered by artificial nutrition did not differ between COVID-19 and non-COVID-19 patients. It is true that the former needed higher rates of insulin infusion, but this could be related to the use of glucocorticoids as part of their treatment. In the present study, we have also shown that the amount of glucose delivered through parenteral nutrition was associated with higher glycemia at ICU independently of COVID-19 diagnosis.An important limitation of our study is that it was enabled to find differences in ICU stay and serum osteocalcin but not in the composition of artificial nutrition. In this regard, we showed after performing a multivariate analysis that both ICU stay and osteocalcin were independently associated with COVID-19 diagnosis and the presence of stress hyperglycemia. However, the latter were also associated with longer artificial nutrition support and higher energy needs, so the design of our study precludes us from reaching valid, nonbiased associations regarding artificial nutrition. Therefore, future studies are needed to address the role of the type and composition of artificial nutrition in critically ill COVID-19 patients.Hyperglycemia in critically ill COVID-19 patients was associated with longer ICU stays and with higher amounts of glucose delivered through artificial nutrition in both COVID-19 and non-COVID-19 patients. Low circulating osteocalcin was a good marker for stress hyperglycemia.


Background: As chemical signals of hormones, neuropeptides are essential to regulate cell growth by interacting with their receptors to achieve cell communications in cancer tissues. Previously, neuropeptide transcriptome analysis was limited to tissue-based bulk expression levels. The molecular mechanisms of neuropeptides and their receptors at the single-cell level remain unclear. We conducted a systematic single-cell transcriptome data integration analysis to clarify the similarities and variations of neuropeptide-mediated cell communication between various malignancies. Methods: Based on the single-cell expression information in 72 cancer datasets across 24 cancer types, we characterized actively expressed neuropeptides and receptors as having log values of the quantitative transcripts per million ≥ 1. Then, we created the putative cell-to-cell communication network for each dataset by using the known interaction of those actively expressed neuropeptides and receptors. To focus on the stable cell communication events, we identified neuropeptide and downstream receptors whose interactions were detected in more than half of all conceivable cell-cell interactions  in a dataset. Results: Focusing on those actively expressed neuropeptides and receptors, we built over 76 million cell-to-cell communications across 70 cancer datasets. Then the stable cell communication analyses were applied to each dataset, and about 14 million stable cell-to-cell communications could be detected based on 16 neuropeptides and 23 receptors. Further functional analysis indicates these 39 genes could regulate blood pressure and are significantly associated with patients’ survival among over ten thousand The Cancer Genome Atlas (TCGA)pan-cancer samples. By zooming in lung cancer-specific clinical features, we discovered the 39 genes appeared to be enriched in the patients with smoking. In skin cancer, they may differ in the patients with the distinct histological subtype and molecular drivers. Conclusions: At the single-cell level, stable cell communications across cancer types demonstrated some common and distinct neuropeptide-receptor patterns, which could be helpful in determining the status of neuropeptide-based cell communication and developing a peptide-based therapy strategy. Malignant tumors seriously threaten human life and health and currently still maintain a high morbidity and mortality rate worldwide. According to worldwide statistics in 2020, there will be approximately 19.3 million new cancer cases and approximately 10.0 million deaths [A neuropeptide is an endogenous peptide that exists in the central nervous system and participates in the function of the nervous system . As shorTo date, tissue-based gene expression technology could measure the averaged gene expression in a sample containing millions of cells. Although this can identify differentially expressed genes and transcripts in different cell populations, many subtle differences between cells in the same tissue sample will be overlooked. Combined with high-throughput cell isolation, Single-cell RNA-sequencing (scRNASeq) is a new technology for high-throughput sequencing of mRNA at the single-cell level . scRNASeTo compare the neuropeptide in different cancers, we utilized the pre-computed database CancerSEA . By focuOur previous work about the copy number changes of neuropeptides collected a total of 93 human neuropeptide precursors in cancers ; and twoBy mapping to all the downloaded expression data from CancerSEA, all 226 neuropeptides and receptor genes’ expression data were extracted. We defined genes that are actively expressed for each data set if the log2 transformed TPM value of a neuropeptide or its receptor is equal to or greater than 1. In this way, we can summarize the active expression status of all neuropeptides and receptors in each cell. Then, the relationships between cells were further established through the known interaction between neuropeptides and their receptors . FinallyTo define stable cell communication, we calculated a stable cell communication ratio based on the active expressed neuropeptides and receptors in a dataset:x represents the number of cell-cell communication based on active expressed neuropeptide-receptor pairs. y depicts the total cells in the dataset. Therefore, y2 is all of the potential cell-cell communication in the corresponding dataset. When the stable expression ratio is over 50%, we defined this neuropeptide-receptors pair as a stable cell communication in this dataset. Based on this criterion, we identified stable neuropeptide-receptor interaction pairs in all 70 datasets.In the equation, For the 39 stably expressed neuropeptides and their receptors in multiple scRNASeq datasets, we conducted a further systematic mutational and survival analysis using a large amount of public cancer genomics data. By using cBioportal , we calcp-value calculation. In this article, the neuropeptide receptor network was displayed based on Cytoscape [Regarding the enrichment of oncogenes and tumor suppressor genes, we downloaded all known oncogenes and tumor suppressor genes from ONGene  and TSGeytoscape .To explore the cell state related to neuropeptides and receptors, we utilized an R package GSVA . To quanUnprecedented chances to investigate the functional heterogeneity of cancer cells are now available thanks to a significant amount of published scRNAseq transcriptome data. Our analysis pipeline is based on two types of information to detect neuropeptides and receptors-based cell communications at a single-cell level . One is In our published work , we collNXPH1-NRXN1 is involved in almost 61%  of all conceivable cell-to-cell communications in the dataset.Even though there are only 214 distinct actively expressed neuropeptide and receptor genes, they have built up massive cell-to-cell communication networks. For instance, we found 76,804,316 cell-to-cell interactions in 70 datasets spanning 24 cancer types. It was necessary to eliminate two datasets since the actively expressed neuropeptides and receptors were not detected in the two datasets. The NXPH1-NRXN1 pair is the most common cell communication pair among them. In a dataset featuring oligodendroglioma (GSE70630) [Identifying stable and reproducible expression across a range of abundances may be helpful to score gene signatures and normalize transcriptomic data across cells . We defiBy applying this criterion to all the 70 datasets, we only identified 26 unique actively and stably expressed neuropeptide-receptor pairs. In fact, stable cell communication analysis also narrowed down the number of scRNASeq datasets from 70 to 38. In addition, we defined 39 genes (16 neuropeptides and their 23 receptors) as the stably expressing neuropeptide network involved in 14,014,088 cell-to-cell communications across 17 cancer types. Due to the importance of these 39 genes, our subsequent analysis conducted a more in-depth signature and survival analysis.To explore the role of neuropeptides at the single-cell level, we compared the cell communications initiated by all neuropeptides across 24 cancer types A. All neBy classifying these neuropeptides according to the protein family, we have statistics about the unique active neuropeptides in 24 cancer types B. In praCORT neuropeptide being the most linked. Module4 is also highly expressed and plays a critical function in liver cancer. Module 4 has 17 genes, including 6 neuropeptides such as KNG1. Consequently, a substantial number of neuropeptides and their receptors have a strong cancer-type specificity in their expression. In sum, there are a lot of neuropeptide receptors that cannot be categorized by neuropeptide family or functional module. This could also mean that those unclassified neuropeptides may regulate cellular processes through orphan receptors.Based on our previously identified functional module, we further compared the expression pattern of different modules among various cancer types. We discovered that diverse forms of cancer are influenced by a vast number of disconnected (unknown module) neuropeptides and receptors. We might also be able to uncover some cancer type-specific modules. Glioma, for example, has a high concentration of module 2. Module 2 has 39 genes, including 15 neuropeptides and 24 receptors, with the In the first stage, we built 76,804,316 cell-to-cell interactions from 70 single-cell expression datasets from cancer patients. We are now ready to execute the stable expression analysis in order to focus on reproducible and stable cell communications. Each neuropeptide-receptor interaction must be observed in more than half of all conceivable cell communications, according to the criteria. The square of cells in a dataset was used to represent all conceivable cell communications. Then, we determined how extensive each neuropeptide-receptor pair is by comparing the cell communication initiated by each neuropeptide-receptor pair. As a result, we were able to decrease the original 70 datasets to just 38. In detail, 16 neuropeptides and 23 receptors were primarily responsible for those cell communications . It is wAs shown in p-value is about 2.615 × 10−4, indicating that 39 genes are significantly associated with patient survival across multiple cancer types. As shown in To further assess the potential functions for these 39 neuropeptides and receptors, we utilized the TCGA pan-cancer genomics data to examine if they are related to patient prognostic features. Of the 10,803 patients from 32 cancer cohorts, 4502 cases have specific genetic mutations among these 39 genes. The median survival time is about 68.94 months compared to 88.50 months from the 6301 cancers without mutations in the 39 genes. The log-rank test p-value = 1 × 10−18.68). As a common side effect of cancer treatment, high blood pressure is particularly important for chemotherapy and targeted therapy. And these genes are also crucial for heart development, response to insulin, learning, and memory.The additional functional enrichment analysis was performed to examine the key molecular mechanisms underlying these 39 genes. As shown in NRXN1 (595 samples), LRP5 (529 samples), NRXN3 (452 samples), and SDC2 (437 samples). We could detect mutations on NRXN1 and NRXN3 in 950 cancer samples across 32 cancer types. Generally speaking, this result may indicate the importance of the neurexins family in various cancer development. Our cell communication evidence at the single-cell level may provide the potential mechanisms underlying the neurexins.By focusing on the mutational frequency of each gene , we coulp-values , KNG1 (441 samples ~12%), AGTR1 , and NRXN3 .Since we found the lung cancer and melanoma have the highest mutational rate in 39 genes, our second set of analyses were focused on these two cancer types . By expap-values A, which p-values C. This mSimilarly, another 2799 skin cancer samples were combined from 18 studies using cBioPortal D–F. Of tNXPH1-NRXN1 is the leading interaction associated with most cell communications, we used the oligodendroglioma dataset as an example to demonstrate the neuropeptide-receptor cell status (GSE70630) [We further assessed each cell sample’s neuropeptide receptor status characteristics in the 38 data sets involved using the 39 genes. In addition, the neuropeptide-receptor status was correlated to the other cell states systematically. Since SE70630) .As shown in To summarize, we have for the first time investigated the interplay of neuropeptides and their receptors in diverse malignancies at the single-cell level. Our findings revealed not only the first comprehensive neuropeptide single-cell interaction map but also 39 valuable biomarker genes that can be exploited to detect cancer prevalence and progression at the single-cell level. We may examine how active neuropeptide-initiated communications are by identifying a set of stably expressed neuropeptide-receptor couples whose expression levels and communication broadness should not vary considerably under different experimental settings. We discovered that 39 stably expressed neuropeptides and their receptor genes are directly associated to prognostic and survival indicators of diverse malignancies after integrating a massive amount of cancer genomics data. These methods may provide a clear direction for the ongoing development of neuropeptide-based pharmacological treatments since neuropeptides and their receptors can deliver novel hormone-based treatments with low adverse effects.To reconstruct the communication network between cells, we only looked at neuropeptides with identified receptors. As a result, neuropeptides with unknown receptors may go unnoticed. In addition, the ligand-receptor data we used was published in 2015 . TherefoA reference list of stably expressed genes will be valuable for expression normalization in transcriptome analysis . This stSince 1961, evidence has accumulated indicating neurotransmitters and peptides such as vasopressin, neurotensin, thyrotropin-releasing hormone, somatostatin, substance P, enkephalins, opioid peptide, and endorphin may play a role in blood pressure management . RecentlNRXN1 and NRXN3). The NRXN1 with epidermal growth factor-like (EGF-like) domain has been shown to interact with neurexophilins [NRXN3 has been associated with alcohol or drug addiction [One of the most important features of our analysis is the stable and active expression of neurexins  and driver mutational patterns.


Is the prevalence of therapeutic inertia for the treatment of hypertension similar across racial and ethnic participant groups?In this secondary cross-sectional analysis of 8556 participants in the Systolic Blood Pressure Intervention Trial , among participants with blood pressure above their randomized treatment goal, therapeutic inertia occurred at similar frequencies among non-Hispanic White and Hispanic participants but was lower among non-Hispanic Black vs non-Hispanic White participants.These findings suggest that implementing highly standardized blood pressure measurement and treatment protocols in clinical practice, such as those imposed in clinical trial settings, may reduce racial and ethnic disparities in blood pressure control. This cross-sectional study examines whether racial and ethnic differences were present for therapeutic inertia among participants in the Systolic Blood Pressure Intervention Trial. Therapeutic inertia may contribute to racial and ethnic differences in blood pressure (BP) control.To determine the association between race and ethnicity and therapeutic inertia in the Systolic Blood Pressure Intervention Trial (SPRINT).This cross-sectional study was a secondary analysis of data from SPRINT, a randomized clinical trial comparing intensive (<120 mm Hg) vs standard (<140 mm Hg) systolic BP treatment goals. Participants were enrolled between November 8, 2010, and March 15, 2013, with a median follow-up 3.26 years. Participants included adults aged 50 years or older at high risk for cardiovascular disease but without diabetes, previous stroke, or heart failure. The present analysis was restricted to participant visits with measured BP above the target goal. Analyses for the present study were performed in from October 2020 through March 2021.Self-reported race and ethnicity, mutually exclusively categorized into groups of Hispanic, non-Hispanic Black, or non-Hispanic White participants.Therapeutic inertia, defined as no antihypertensive medication intensification at each study visit where the BP was above target goal. The association between self-reported race and ethnicity and therapeutic inertia was estimated using generalized estimating equations and stratified by treatment group. Antihypertensive medication use was assessed with pill bottle inventories at each visit. Blood pressure was measured using an automated device.A total of 8556 participants, including 4141 in the standard group  and 4415 in the intensive group  with at least 1 eligible study visit were included in the present analysis. Among non-Hispanic White, non-Hispanic Black, and Hispanic participants, the overall prevalence of therapeutic inertia in the standard vs intensive groups was 59.8%  vs 56.0% , 56.8%  vs 54.5% , and 59.7%  vs 51.0% , respectively. The adjusted odds ratios in the standard and intensive groups for therapeutic inertia associated with non-Hispanic Black vs non-Hispanic White participants were 0.85  and 0.94 , respectively. The adjusted odds ratios for therapeutic inertia comparing Hispanic vs non-Hispanic White participants were 1.00  and 0.89  in the standard and intensive groups, respectively.Among SPRINT participants above BP target goal, this cross-sectional study found that therapeutic inertia prevalence was similar or lower for non-Hispanic Black and Hispanic participants compared with non-Hispanic White participants. These findings suggest that a standardized approach to BP management, as used in SPRINT, may help ensure equitable care and could reduce the contribution of therapeutic inertia to disparities in hypertension.NCT01206062ClinicalTrials.gov identifier:  However, data on racial and ethnic differences in therapeutic inertia in hypertension are limited, and the available data are conflicting. Some studies suggest that therapeutic inertia may be higher, while others show similar or lower prevalence, in Black vs White adults with hypertension.14 By studying racial and ethnic differences in hypertension-related therapeutic inertia in a clinical trial in which BP care was standardized and protocolized, targeted interventions could be developed and prioritized to improve BP management in all racial and ethnic groups, potentially leading to reduced disparities in BP control and hypertension-related CVD.The root causes of disparities in BP control are multifactorial and can be attributed to patient-related, clinician-related, and health care system–related barriers.We tested whether racial and ethnic differences in therapeutic inertia in hypertension were present when BP care was standardized and protocolized. To do so, we used data from the Systolic Blood Pressure Intervention Trial (SPRINT), which randomized US adults with high CVD risk to intensive  vs standard treatment  and used a standardized approach to both BP measurement and treatment. The SPRINT protocol required intensification of antihypertensive medication if SBP was not at goal. This design allowed for a quasinatural experimental comparison of therapeutic inertia by race and ethnicity in a randomized clinical trial in which BP management was standardized across racial and ethnic groups, including access, measurement, and treatment. Using SPRINT data, we sought to determine the association between self-reported race and ethnicity  and therapeutic inertia in hypertension management.STROBE) guideline for reporting observational analyses.15 Each SPRINT site’s institutional review board approved the primary study protocol, and written informed consent was obtained from each participant. This secondary analysis was determined to be exempt by the University of Utah’s institutional review board because the project did not meet the definition for human participant research according to federal regulations.The current serial, cross-sectional, secondary analysis of SPRINT adheres to the Strengthening the Reporting of Observational Studies in Epidemiology  of less than 20 mL/min/1.73 m2 were excluded. Participants were followed monthly for the first 3 months and then every 3 months thereafter (median follow-up time 3.26 years). Additional study visits were available monthly for medication titration. Participating clinicians were encouraged to add an antihypertensive medication or up-titrate the dose until the SBP goal was achieved. To minimize the likelihood of therapeutic inertia, SPRINT mandated the use of milepost visits every 6 months in the intensive group, but not the standard group, at which time BP was measured, and a new medication was added if necessary.18 Because of this design element, we stratified all analyses by treatment group. Antihypertensive medications were provided free of charge at each participant visit with sufficient medication to last through the next follow-up visit without the need for pharmacy fills outside of the trial. We restricted the analysis to participant visits where SBP was above the randomized treatment goal within each treatment group. We excluded participant visits where SBP was at or below goal, as therapeutic inertia can only occur at participant visits where the SBP is above goal.The rationale, design, and primary results of SPRINT have been published.There were 9361 participants randomized to either intensive treatment (4678 participants) or standard treatment (4683 participants). After restricting the sample to study visits where SBP was above target goal, there were 4141 and 4415 unique participants with at least 1 visit with measured SBP above the target goal, representing 22 844 and 35 453 participant-visits in the standard and intensive treatment groups, respectively .Self-reported race and ethnicity, categorized as Hispanic, non-Hispanic Black, and non-Hispanic White, was the primary exposure for analysis. Participants were first identified by self-reported ethnicity, categorized as Hispanic or non-Hispanic. Then, participants were categorized by self-reported race, defined as Black or African American, White or Caucasian, Native American or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, and other. In the current study, 984 participants were included as Hispanic irrespective of self-identified race. Participants who identified as non-Hispanic and Black or African American alone were included as non-Hispanic Black (n = 2802). Participants who identified solely as White were included as non-Hispanic White (n = 5399). We could not analyze Native American or Alaska Native, Asian, Native Hawaiian or other Pacific Islander owing to low sample size, as these groups represented less than 3% of the study sample.The primary outcome, therapeutic inertia, was defined as no change or a reduction in the participant’s antihypertensive medication regimen intensity during a study visit when SBP was measured at or above the assigned target goal . The unit of analysis for therapeutic inertia was each unique study visit. Change in the antihypertensive medication regimen intensity was quantified using the modified therapeutic intensity score (mTIS). Detailed description of how the mTIS was calculated in SPRINT is provided in the eMethods in the 18 Blood pressure was measured at baseline and each study visit using an automated device  following a standardized procedure by trained clinical staff.19 Because treatment-related serious adverse events (SAE) can influence therapeutic inertia, we included treatment-related SAEs of interest  occurring in the 1 month before each visit in the current analysis as a covariate.18Participants’ sociodemographic data were collected at baseline. Clinical, laboratory, and medication data were collected at baseline and every 3 months thereafter by trained study personnel.18 Second, the intensive treatment group had approximately 10% more total study visits than the standard treatment group. Analysis was restricted to the first 48 months of follow-up, as sample sizes decreased substantially thereafter.All analyses were stratified by the treatment group (intensive vs standard) for 2 reasons. First, the intensive treatment group mandated milepost visits every 6 months to ensure that antihypertensive intensification was occurring in concordance with SPRINT protocol, whereas the standard treatment group did not have milepost visits.P values were calculated for comparison of characteristics by race and ethnicity only (not therapeutic inertia). This calculation was done by t tests or Kruskal Wallis tests when appropriate for parametric or nonparametric continuous variables, and χ2 tests for comparison of categorical variables. Tests were all 2-seded with a P value cutoff of <.05. We determined the association between race and ethnicity and therapeutic inertia during SPRINT follow-up using a multivariable generalized estimating equation model to account for within-subject correlation. An adjusted odds ratio (OR) and 95% CI for therapeutic inertia associated with self-reported race and ethnicity was generated with non-Hispanic White as the reference group. Five nested models were created. Model 1 included race and ethnicity and follow-up time as the only fixed effects. Model 2 included variables in model 1 in addition to adjustment for sociodemographic variables and baseline values of clinical measurements , from October 2020 through March 2021.Baseline characteristics were compared by self-reported race and ethnicity . A total of 8556 participants were included in analyses. In the standard treatment group of 4141 participants , 384 were Hispanic (9.3%), 1305 were non-Hispanic Black (31.5%), and 2451 were non-Hispanic White (59.2%). In the intensive treatment group of 4415 participants , 447 were Hispanic (10.1%), 1329 were non-Hispanic Black (30.1%), and 2639 were non-Hispanic White (59.8%).In both the standard and the intensive treatment groups, compared with non-Hispanic White participants, non-Hispanic Black and Hispanic participants were younger; had a higher proportion of participants who were female, uninsured, with no usual source of care, and never smokers; and had a lower proportion with a high school education or less, who were retired, and who were taking a statin or aspirin . MissingIn the standard treatment group, the overall prevalence of therapeutic inertia was 59.8% , 56.8% , and 59.7%  among non-Hispanic White, non-Hispanic Black, and Hispanic participant-visits, respectively . The adjAfter adjustment for patient sociodemographic data, follow-up values of clinical measurements, mTIS reported at the prior visit, and treatment-related SAEs occurring within 1 month before the study visit (model 3), the OR for therapeutic inertia was 0.85  comparing non-Hispanic Black vs non-Hispanic White participants . When coThe overall prevalence of therapeutic inertia across all included visits in the intensive group was 56.0% , 54.5% , and 51.0%  among non-Hispanic White, non-Hispanic Black, and Hispanic participant-visits, respectively. Compared with the standard group, the increase in the adjusted predicted probability of therapeutic inertia over time was greater in the intensive group B. At 12 Comparing non-Hispanic Black vs non-Hispanic White participants, after adjustment for patient sociodemographic data, follow-up values of clinical measurements, mTIS reported at the prior visit, and treatment-related SAEs within 1 month prior to the study visit (model 3), the OR for therapeutic inertia was 0.94  . The mulIn the multivariable-adjusted model (model 3) including all 3 racial and ethnic groups in the standard treatment group, follow-up time, older age, private insurance, higher eGFR, higher serum potassium, greater prior mTIS, calcium channel blocker use, and thiazide diuretic use were associated with a greater likelihood of therapeutic inertia (eTable 5 in the In the multivariable-adjusted model (model 3) including all 3 racial and ethnic groups in the intensive treatment group, follow-up time, older age, greater prior mTIS, and thiazide diuretic use were associated with a greater likelihood of therapeutic inertia  vs patient-level factors  contribute to this disparity. Medication adherence is often attributed as a driver of disparities in BP control. Separate analyses of patients with Medicare and private insurance suggest that nonadherence to antihypertensive medications is more common in non-Hispanic Black and Hispanic patients.25 However, this association is attenuated after adjustment for other socioeconomic variables and fails to entirely explain the disparities in BP control by race and ethnicity.25Despite similar awareness and treatment rates in the US, non-Hispanic Black and Hispanic adults continue to have substantially lower BP control rates compared with non-Hispanic White adults.12 In a study of adults with hypertension on antihypertensive medication, treatment intensification with additional antihypertensive medication occurred in only 13.8%, 10.3%, and 10.5% of visits for non-Hispanic Black, Hispanic, and non-Hispanic White adults, respectively.26 When studying patients with hypertension from a safety-net hospital, Manze et al13 found higher rates of therapeutic inertia for Black patients. The current report suggests therapeutic inertia is either similar or lower in non-Hispanic Black and Hispanic adults compared with non-Hispanic White adults when care is standardized and protocolized as in SPRINT.Data on racial and ethnic differences in therapeutic inertia, defined as the act of not intensifying a medication regimen despite being indicated, is limited and conflicting. One multicenter cohort of 16 881 hypertensive adults showed therapeutic inertia to occur in 67.9% of clinic visits for Black patients and 72.2% in White patients.29 A simulation by Bellows et al30 found that medication intensification was the most influential of the multiple interventions to achieve BP control. In community practice, therapeutic inertia is estimated to be present in more than 80% of clinic visits.26 In one analysis of managed care patients, clinicians increased antihypertensive medication in only 13% of visits where BP was uncontrolled.31 In the current analysis, therapeutic inertia was present in 50% to 60% of participant visits with uncontrolled BP. Although this rate is lower than estimates of therapeutic inertia in community practice, the prevalence was only slightly lower than the 60% to 70% reported in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).32 Although protocolization of care may be a significant driver of our findings, it is also possible that the overarching medical support available to participants of a clinical trial may have implications for addressing both therapeutic inertia and racial disparities in therapeutic inertia.Therapeutic inertia has been identified as a key clinician-level barrier to BP control.34 Additionally, Kaiser Permanente Northern California has shown that a standardized approach to hypertension treatment can achieve parity in BP control between Black and White patients, with BP control exceeding 80% in both patient populations.35 Kaiser Permanente uses several strategies to reduce therapeutic inertia, including maintaining a system-wide hypertension registry, prioritizing evidence-based practice guidelines and fixed-dose combination therapy, and using medical assistants for follow-up measurements.37 While the SPRINT protocol for BP management represents one approach to standardizing BP care, other standardized approaches, such as the Measure Accurately, Act Rapidly, and Partner with Patients program and the Kaiser Permanente algorithm, demonstrate multiple effective strategies to minimize therapeutic inertia.37 In addition to implementing care protocols to reduce therapeutic inertia, health systems should encourage the use of fixed-dose combination medication , follow-up every 2 to 4 weeks after initiation or titration of drug therapy until BP goal is achieved, team-based care, and personalized feedback to clinicians.38 Greater implementation of patient-centered strategies are needed in community care of adults with hypertension.40 Ongoing studies focused on team-based hypertension care, mobile health platforms, and home BP monitoring will provide more evidence on interventions that increase patient engagement and reduce therapeutic inertia.38Prior research suggests that a standardized approach to BP management can increase BP control. For example, the American Medical Association’s Measure Accurately, Act Rapidly, and Partner with Patients BP Improvement Program reduced racial and ethnic disparities in BP control through addressing therapeutic inertia.8 By mandating antihypertensive medication intensification when BP was above target in SPRINT, inappropriate inaction  was reduced, though not eliminated. For example, the current analysis adjusted for prior mTIS and the number of antihypertensive medications being taken, which were associated with greater therapeutic inertia. Clinicians might have been less likely to intensify an antihypertensive regimen if a patient was already taking a high dose or multiple antihypertensive medications. In contrast, the influence of appropriate inaction  on antihypertensive medication underuse is difficult to ascertain. All participants in SPRINT received education and counseling regarding physical activity, diet, smoking cessation, and weight management in order to minimize the effect that lifestyle modification may have on therapeutic inertia. Additionally, treatment-related SAEs were not associated with therapeutic inertia in either treatment group in the current analysis.In SPRINT, BP measurement and antihypertensive medication intensification were protocolized. This approach differs from usual community practice in which competing demands, time constraints, and clinical uncertainty in BP measurement can impact appropriate care delivery.There are several strengths and limitations of the current analysis. The Systolic Blood Pressure Intervention Trial was a large, racially and ethnically diverse, randomized clinical trial with high-quality BP measurement and detailed medication use including dosing levels at least every 3 months. Furthermore, the SPRINT treatment protocol achieved a large difference in SBP between treatment groups for the duration of the trial. The design of SPRINT allows for observation of therapeutic inertia in an environment where access, cost, and the approach to BP measurement and treatment are equal and standardized for all trial participants. However, as with all observational studies, there may be residual confounding. Unlike the intensive group, the standard group only indicated intensification if a participant was above SBP goal at 2 consecutive visits. Although the difference in protocol may translate into different intensification patterns between the standard and intensive groups, this limitation is addressed in the current study by stratifying the analysis by treatment group and the included sensitivity analyses defining therapeutic inertia as 2 consecutive visits without intensification for both treatment groups and as an SBP of 160 mm Hg or great or 2 consecutive study visits with an SBP of 140 mm Hg or greater in the standard group only. The current analysis did not evaluate the association between therapeutic inertia and BP control or antihypertensive intensification at subsequent study visits. Additionally, all interactions existed within the framework of a randomized clinical trial, limiting generalizability to community-treated patients in routine care. Finally, the SPRINT protocol mandated the use of milepost visits in the intensive group only, limiting direct comparisons of therapeutic inertia between study groups.In this cross-sectional study using data from SPRINT, therapeutic inertia was either similar or lower among non-Hispanic Black and Hispanic participants compared with non-Hispanic White participants. Therapeutic inertia represents a significant barrier to BP control, particularly among racial and ethnic minority populations. The findings of the current analysis indicate that well-resourced, protocolized, and standardized BP management—including BP measurement and medication initiation and intensification—may be an effective strategy to address racial and ethnic disparities in BP control driven by therapeutic inertia.


This article reviews a study to determine the effects of COVID-19 on the rate of depression and anxiety in nurses and to identify potential strategies that nurse leaders can implement to reduce depression and anxiety in their staff. The World Health Organization declared COVID-19 a pandemic on March 11, 2020, as the novel virus spread rapidly across the globe.3Increased rates of depression and anxiety among nurses working in the COVID-19 environment isn't unexpected because the clinical trajectory of COVID-19 still isn't well understood and the risks are unclear. Psychological stressors contributing to mental health distress have ranged extensively during the pandemic, including shortages of personal protective equipment (PPE), limited access to COVID-19 testing supplies, fear of disease transmission at work, fear of lack of employer support if COVID-19 is contracted, depression when patients succumb to the virus, ethical decisions regarding care rationing, and drastic changes in workplace practice.5In addition, organizational policies have frequently changed as new knowledge of disease transmission and treatment options emerge. Frequent policy changes on prevention strategies and treatment plans, and poor communication of changes or accessibility of information, negatively affect nurses' mental health.4The aims of this study were to determine the effects of COVID-19 on the prevalence of depression and anxiety in nurses and to identify potential strategies that nurse leaders can implement to reduce depression and anxiety in their staff.This study is part of a larger study that was conducted at Arrowhead Regional Medical Center (ARMC) to determine the prevalence of depression and anxiety and elucidate associations between sociodemographic variables, depression, and anxiety. ARMC is a 456-bed university-affiliated teaching public hospital that serves as a safety net hospital for the uninsured and underserved population in San Bernardino County, Calif.11The design for the original study was an anonymous cross-sectional convenience sample survey using an online survey platform. The survey's web link was emailed to nursing administration clinical assistants (CAs), student nurses (SNs), licensed vocational nurses (LVNs), registered nurses (RNs), and advanced practice nurses (APNs). Prospective participants were recruited from an all-users email sent by ARMC's chief executive officer. The survey was open for responses between April 30 and May 22, 2020. Inclusion criteria included being older than age 18; working in the hospital as a CA, SN, LVN, RN, or APN; being willing and able to give informed consent; and being able to complete the survey in English. This study was approved by ARMC's Institutional Review Board. During the study period, the number of confirmed COVID-19 cases doubled from 2,058 to 4,146 in San Bernardino County.The Patient Health Questionnaire 9 (PHQ-9) was used to measure self-reported levels of depression. The PHQ-9 consists of nine questions to measure the frequency of depressive symptoms over the past 2 weeks on a four-point Likert scale ranging from 0  to 3 (nearly every day). Scores are interpreted as 0 to 4, normal; 5 to 9, mild; 10 to 14, moderate; 15 to 19, moderately severe; and 20 to 27, severe. PHQ-9 scores were categorized into two groups: <10 and ≥10. A PHQ-9 score ≥10 is categorized as major depression and is 88% sensitive and specific.12The General Anxiety Disorder 7 (GAD-7) scales were used to measure self-reported levels of anxiety. The GAD-7 consists of a seven-item questionnaire to measure the level of anxiety symptoms over the past 2 weeks using a four-point Likert scale ranging from 0  to 3 (nearly every day). The scores are interpreted as 0 to 4, normal; 5 to 9, mild; 10 to 14, moderate; and 15 to 21, severe. GAD-7 scores were divided into two groups: <8 and ≥8.13Data collected from staff included sex, age, occupation, years in current position, contact with a patient suspected of having or confirmed as having COVID-19, and feeling overwhelmed by COVID-19. Participants were classified into four groups: CA/SNs, LVNs, RNs, and APNs. These groups were further divided in two categories: staff providing direct care for suspected or confirmed COVID-19 patients and staff not exposed or not providing direct care for suspected or confirmed COVID-19 patients. Questions included, “Have you been in contact with a patient either suspected to have COVID-19 or confirmed to have COVID-19?” Staff members who answered “yes” were classified as providing direct care for suspected or confirmed COVID-19 patients and those who answered “no” were classified as not providing direct care for suspected or confirmed COVID-19 patients. The question “Have you been overwhelmed by the stress of the COVID-19 pandemic?” was asked to determine perceived stress measurement. Studies have validated that perceptions of stress can be measured by asking individuals how overwhelmed they are by a situation.P value of ≤.05 was considered statistically significant.All statistical analyses were conducted using statistical software.A total of 472 nurse participants responded to the survey and were included in the final analysis (survey response rate = 29.5%). The majority of the participants were female  and the average age was 42.9 (SD = 11.6). More than two-thirds of participants were RNs or APNs . Overall, 48.7% (n = 227) of participants were overwhelmed by COVID-19. (See Table P = .0007). Participants who didn't have contact with suspected or confirmed COVID-19 patients (P = .0344) had higher PHQ-9 scores  and higher GAD-7 scores , which was associated with a higher chance of being stressed by COVID-19.  of self-reported stress due to COVID-19 than RNs or APNs  of having moderate-to-severe depression.  compared with RNs and APNs. Additionally, those who self-reported that they were overwhelmed by COVID-19 were associated with 7.31 times higher rates  of moderate-to-severe anxiety. (See Table Before the COVID-19 pandemic, data regarding the effect of unprecedented high-pressure work environments on nurses' mental health were limited.5During the pandemic, nurses have worked under intense pressure, which can negatively affect their resilience.17This study noted that female nurses were more likely to be distressed compared with male nurses and two times more likely to experience a greater psychological burden.A possible explanation for the disparity in depression and anxiety rates is that historically women report more honest responses to questions regarding anxiety.23An unexpected finding in this study was that nurses who didn't provide direct patient care for suspected or confirmed COVID-19 patients had statistically significant higher reported depression and anxiety scores. Literature is scant on the various nursing roles, scope of practice, and prevalence rates of depression and anxiety during a pandemic. This study found that CAs/SNs and LVNs reported higher levels of depression and anxiety than RNs or APNs. These results are consistent with previous studies that also reported an association between nursing practice roles and increased depression and anxiety.26Potential causes of increased depression and anxiety in CAs/SNs and LVNs may be attributed to their scope of practice and exposure to COVID-19 patients. Limited access to educational resources and inadequate support and oversight by RNs and APNs due to the stressful environment and working conditions may also be contributing factors.This study had several limitations. Causality can't be established due to the cross-sectional nature of the study. The voluntary web-based survey may have created a selection bias. There were more female participants than male participants, which may have caused a self-selection bias. The results may not be generalizable due to the study taking place at only one organization.Future research should focus on gathering a larger sample size of nurse participants, recruiting more male nurses, and participating in a multicenter study to validate reported findings. In addition, future studies should aim to investigate factors that correlate nursing roles and scope of practice with depression and anxiety prevalence. Additionally, factors that affect and improve nurses' resilience to reduce depression and anxiety should be investigated.The COVID-19 pandemic has highlighted a gap in the mental health needs of nurses during extended high-intensity conditions. Nurse leaders play an important role in reducing adversity and stress in nurses by creating an environment that nurtures personal resilience and social and organizational support.28These strategies can be divided into professional and personal environment needs. Professional environment needs include clear communication regarding updates on the infectious disease, use and management of PPE, patient flow, and policy changes. Providing easily accessible training and care protocols may reduce anxiety associated with unfamiliarity and feelings of lack of control.29Preplanning and implementation of mental health action plans are essential to enhance psychological resilience and strengthen the healthcare system and nursing workforce.33This study noted that depression and anxiety were prevalent among all levels of nursing staff, although CAs, SNs, and LVNs were particularly vulnerable to variable negative mental health outcomes. Moreover, elevated stress levels were associated with clinically significant depression and anxiety. If left untreated, psychological distress can have long-term negative consequences that lead to burnout and poor patient care. Therefore, it's imperative that hospital systems develop supportive plans for nurses that are tailored to strengthen their mental health as part of disaster preparedness.


Our understanding of the risk of developing severe coronavirus disease 2019 (COVID-19) infection in the population living with HIV is still evolving. In this report, we discuss the successful management of COVID-19-related acute respiratory distress syndrome (ARDS) in an active case of the human immunodeficiency virus (HIV) infection; the patient had an atypical presentation characterized by very rapid progression in the severity of respiratory symptoms needing invasive mechanical ventilation. The way the case was managed broke with the custom that mechanical ventilation in patients with COVID-19-related ARDS should be deferred as much as possible since the chances of survival are minimal, especially in immunocompromised patients. Although patients with HIV infection are immunocompromised and at risk of secondary infection, young age, lack of comorbidities, and early intubation may result in a good prognosis. ARDS ventilation strategy, good infection control practices, and individualized patient care can help to wean patients off mechanical ventilation. Recent evidence does not support the use of antiretroviral drugs for prophylaxis or treatment of COVID-19 infection. The coronavirus disease 2019 (COVID-19) outbreak was declared as a pandemic by the World Health Organization (WHO) on March 11, 2020 . We repo2, following which his saturation improved to 90%. He was intubated and initiated on mechanical ventilation due to impending respiratory failure with the arterial blood-gas analysis showing a PaO2/FiO2 (P/F) ratio of 70. Laboratory investigations were done and a nasopharyngeal swab for COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) was sent. Point-of-care ultrasonography of lungs was done, which showed B profile with basal consolidation in both lungs. The bedside chest X-ray revealed bilateral alveolar consolidation with peripheral distribution suggestive of COVID-19-related ARDS. He was started on injection piperacillin-tazobactam, injection Clexane, and injection methylprednisolone 500 mg intravenous once daily. Prone ventilation was commenced, and subsequently, his P/F ratio improved to 125.A 35-year-old male presented to the emergency of a tertiary care hospital in Central India with complaints of fever with cough and breathlessness for three days. The patient was conscious and oriented but had labored breathing with oxygen saturation of 43% on room air. Non-invasive ventilation (NIV) was initiated with 100% FiOLaboratory reports on day one were notable for severe lymphopenia (4%) and a very high neutrophil-to-lymphocyte ratio (NLR) of 23, suggestive of severe physiologic stress level. RT-PCR assay returned positive and the patient was started on injection remdesivir 200 mg on day one followed by 100 mg for 10 days.3 with a viral load of 24,000 copies/ml. Methylprednisolone was stopped, and injection dexamethasone 8 mg IV twice daily along with Septran-DS (prophylaxis for Pneumocystis jirovecii) was added to the treatment protocol. After three proning sessions in four days, lung compliance markedly improved. However, on day five, the patient developed sepsis and hemodynamic instability, requiring vasopressors. Blood cultures were sent and antibiotics were escalated empirically to injection meropenem 1 gm, injection colistin 3 MIU thrice daily, and injection caspofungin 50 mg once daily. Blood cultures revealed Candida and Acinetobacter, which was pan-sensitive. The tracheal culture was sterile for bacteria and Pneumocystis jirovecii. On day seven of illness, percutaneous tracheostomy (PCT) was done as the patient's P/F ratio was maintained at 180-200. He was weaned off sedation and put on spontaneous/continuous positive airway pressure (CPAP) mode. Subsequently, he was switched to a high-flow cannula through a tracheostomy tube. On day 11, a T-piece trial was given with minimal oxygen flow of 3 l/minute, followed by a trach-vent filter on room air. As he was maintaining oxygen saturation with adequate cough and intact sensorium, he was decannulated on day 12. Paired nasopharyngeal and throat swab for COVID-19 RT-PCR was repeated, which returned negative. The patient was thus discharged and advised to follow up after 10 days.The patient's young age and lack of comorbidities were pointing against the rapid progression of the disease and clinical deterioration. Thus, the HIV ELISA test was sent, which came back positive. Past history revealed that he was a known HIV-positive case and was on antiretroviral therapy (ART) for the last five months. He was on a combination regimen of dolutegravir, lamivudine, and tenofovir. CD4 counts were 177 cells/mm3 and suppressed viral load) [To date, it is not clear if PLHIV are at greater risk of COVID-19 than the general population . Severalal load) . The higal load) .The presentation of the current case was atypical as the patient was of a relatively young age (35 years), and he presented with severe ARDS needing invasive ventilation within three days from the onset of symptoms. With such atypical presentations, HIV could be a risk factor for the rapid progression of the disease in the absence of any other risk factors like advanced age and comorbidities. Since the patient was intubated relatively earlier in the course of the disease and was ventilated under sedation, there was no self-inflicted lung injury (P-SILI), which prevented any parenchymal damage that may have otherwise occurred due to labored breathing pattern at presentation. Early PCT helped him to maintain ventilator synchrony without the need for any sedation. Further, the lack of opportunistic infections due to continued ART leading to low viral counts might have helped in decreasing the severity of the disease and early recovery of the patient.WHO does not recommend the use of antiretrovirals either as a treatment or preventive method for COVID-19. Both the Recovery Trial and WHO multicounty adaptative trial  showed that lopinavir/ritonavir (LPV/r) does not contribute to any reduction in mortality, duration of hospital stay, and risk of progressing to invasive mechanical ventilation or death .Based on our findings, immunocompromised populations such as HIV patients with COVID-19 co-infection can have very atypical presentations with a very rapid progression of the disease. Young age, lack of comorbidities, early hospital admission, and the initiation of invasive ventilation may result in a less turbulent course and better prognosis in this subset. Lung-protective ARDS ventilation strategy, good infection control practices, and tailored patient care can help us in managing these patients successfully. Recent evidence suggests no role for ART in the prophylaxis and treatment of COVID-19 infection.


Endometrial cancer (EC) is the fourth most common cancer in women in developed countries. Although it is usually diagnosed in postmenopausal women, its incidence has increased in young women, as well in recent decades, with an estimated rate of 4% in those under 40 years of age. Factors involved in this increase, particularly in resource-rich countries, include delayed childbearing and the rise in obesity. The new molecular classification of EC should help to personalize treatment, through appropriate candidate selection. With the currently available evidence, the use of oral progestin either alone or in combination with other drugs such as metformin, levonorgestrel-releasing intrauterine devices and hysteroscopic resection, seems to be feasible and safe in women with early-stage EC limited to the endometrium. However, there is a lack of high-quality evidence of the efficacy and safety of conservative management in EC. Randomized clinical trials in younger women and obese patients are currently underway. Endometrial cancer (EC) is the fifth most common cancer in women. Its incidence is increasing in high-income countries, where it is now the fourth most prevalent cancer in women ,2. Over Endometrial hyperplasia is considered a precursor of certain types of endometrial cancer. In the 2014 World Health Organization (WHO) classification, endometrial hyperplasia includes hyperplasia with and without atypia .Progression rates to cancer of 1–5% have been reported for hyperplasia without atypia, and of nearly 25% for hyperplasia with atypia . Kurman EC is commonly observed in postmenopausal women, but between 15% and 25% of cases are found pre-menopause ,13. It hMost endometrial cancer cases are sporadic, with only 3% being associated with Lynch Syndrome . EndometMany factors are associated with the development of endometrial cancer. The main risk factor is obesity because it is associated with peripheral estrogen conversion via aromatization in adipose tissue . Other rThe standard treatment for EC is hysterectomy and bilateral salpingo-oophorectomy (THBSO) with or without lymphadenectomy ,20,21,22Fertility-sparing treatment involves pharmacological and non-pharmacological interventions. The most frequently used are oral progestin, medroxyprogesterone acetate (MPA) or megestrol acetate (MA) ,21,22; oToday, a very high percentage of the European population delay childbearing, a practice that has led to an increasing number of nulliparous women at the time of diagnosis of endometrial cancer. In the US, pregnancy rates increased in women aged >30 from 1990 to 2015 . In thisThe selection of patients with EC for fertility-sparing treatment is important in order to achieve the best outcomes. Current guidelines recommend progestin therapy in stage IA, grade 1 (well-differentiated) endometrioid-type endometrial cancer ,25.In 2015, Rodolakis et al. published guidelines for gynecological oncologists treating women with EC who wish to preserve their fertility. Finally, a consensus was reached between the ESMO, the European Society of Gynecological Oncology, and the European Society for Radiotherapy & Oncology to help identify the ideal candidates for this conservative treatment. The most important points to bear in mind are: first, the assessment of the tumor, including histological type, grade, myometrial invasion, and presence of lymphovascular space invasion; second, the treatment offered, the type, dose, duration of medical intervention, and follow-up .An update published in 2017 recommended the following criteria for fertility-sparing management in EC women: grade 1 EC or atypical endometrial hyperplasia (AEH), histological diagnosis using dilatation and curettage with or without hysteroscopy, and myometrial invasion. Extrauterine disease should be ruled out using pelvic magnetic resonance imaging (MRI) or expert transvaginal ultrasound (TVUS) .The 2018 National Comprehensive Cancer Network (NCCN) includes the following criteria to consider fertility-sparing management of endometrial cancer: well-differentiated (grade 1) endometrioid endometrial carcinoma ; diseaseDilatation and curettage biopsy is recommended for the histologic diagnosis of endometrial cancer. Hysteroscopic biopsy is also a precise diagnostic method for endometrial adenocarcinoma . HoweverMyometrial invasion is another important prognostic factor in patients with endometrial cancer. According to the Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) 26th Annual Report, the 5-year overall survival rate in patients with tumors limited to the endometrium is as high as 90.8%; however, this rate drops to 85.4% when deep myometrial invasion is identified .In the evaluation of myometrial invasion, contrast-enhanced MRI is the preferred method as it offers higher accuracy than TVUS ,19,21,27Recently, the utility of positron emission tomogram (PET) in the detection of lymph node metastases in early-stage endometrial cancer cases has been assessed, with a sensitivity of 63% and a specificity of 94.7% . In a stFertility-sparing treatment of grade 2 endometrioid endometrial cancer is reported in very limited case studies and should only be considered in highly selected individuals with a shared decision-making approach . The mosThere must not be any contraindications to medical therapy or pregnancy. Patients must be informed that the fertility-sparing option is not the standard of care for the treatment of endometrial carcinoma ,25.In 2013, a molecular diagnostic classification published by The Cancer Genome Atlas (TCGA) Research Network defined four prognostic categories: POLE ultra-mutated, microsatellite instability hypermutated, low copy-number tumor, and high copy-number tumor ,31,32. IIn 2019, Britton et al. published a study of the prognostic significance of Proactive Molecular Risk Classifier for Endometrial Carcinoma (ProMisE) in young (<50 years) women with EC. The ProMisE molecular classifier can be applied to endometrial biopsy, demonstrating high concordance with final hysterectomy in this series Ƙ = 0.87, consistent with the literature. It uses pragmatic molecular tests to identify ECs with mismatch repair deficiency (MMRd), mutations in the exonuclease domain of DNA polymerase epsilon (POLE), and wild type or aberrant p53 expression (p53 wt or p53 abn respectively) .The current therapeutic approach to endometrial cancer and atypical endometrial hyperplasia is based on the use of oral progestins such as medroxyprogesterone acetate, megestrol acetate or gonadotropin-releasing hormone agonists ,24,35 orThe goal of hormone treatment is to counterbalance the action of estrogen. Progestogens have antiproliferative actions such as estrogen receptor (ER) and insulin-like growth factor 1 (IGF-1) inhibition and antiangiogenic action . Low-graSeveral randomized controlled trials (RCTs) are currently underway to evaluate the efficacy of LNG-IUS with or without oral progestin or metformin in younger women with low-grade EC ,47,48.Metformin shows several antiproliferative mechanisms: decrease in insulin and IGF-1 levels, increase in progesterone receptor concentration and reduction in progesterone resistance ,50. The Pharmacological interventions, such as appetite suppressants or drugs to reduce fat absorption, may be used to promote weight loss. In obese women, weight-loss interventions (lifestyle interventions) achieved changes in blood biomarkers associated with this cancer . A meta-A review of bariatric surgery treatment for EC prevention concluded that this approach seems to reduce the risk of endometrial cancer, but these results need to be reproduced in randomized clinical trials . BariatrIn addition to weight reduction, there are reports of high rates of improvement, and even cure, of comorbidities associated with obesity, including type II diabetes mellitus, obstructive sleep apnea, hypertension, asthma, osteoarthritis, risk of cancer and gastro-esophageal reflux disease ,58. A meHysteroscopy, as part of a conservative approach to endometrial cancer or atypical endometrial hyperplasia, is controversial. Some authors restrict its use to diagnosis of the tumor and assessment of margins; others explore the possibility of primary treatment plus progestin orally or LNG-IUS, and report excellent complete response rates. Alonso et al.  reviewedRecent studies have confirmed these findings, reporting complete response rates in women with stage 1A EC of 89% to 97% following hysteroscopic fertility-sparing treatment, and pregnancy rates of over 45% ,63. GiamConcerns have been raised about the possible negative obstetric outcomes due to mechanical damage of the endometrium, causing Asherman’s syndrome and raising the risk of placental accretism . More stIn general, fertility-sparing management of endometrial cancer is associated with acceptable rates of progression free-survival (PFS) and overall survival (OS). In a cohort study including 6339 women with endometrial cancer, 161 (2.5%) initially received hormone therapy (HT), and long-term survival for young patients with Grade 1 EC was above 90% after both 10 and 15 years. Initial analyses suggested a higher endometrial cancer-specific 15-year mortality rate in patients treated with HT than in the primary surgery group. The hazard ratio for OS was 1.45  . FurtherIn 2021, Fernández-Montoli et al.  publisheGallos et al.  publisheBaker et al.  publisheKoskas et al.  in 2014 In 2017, Wei et al.  comparedLuo et al.  publisheFan et al.  performeGuillon et al.  publisheChae-Kim et al.  recentlyThe results of these systematic reviews show that fertility-sparing management is possible and safe in patients with atypical endometrial hyperplasia and early-stage endometrial cancer, with complete responses around 75% for oral progestin and 79% for LNG-IUS. Recurrence rate is around 33% for oral progestin but lower with other treatments such as LNG-IUS (11%) and hysteroscopic resection (14%). However, the live birth rate remains low, around 20–48%, despite the various strategies used.Several prospective studies and randomized controlled trials are underway to elucidate the best therapeutic option for patients with endometrial cancer who wish to preserve fertility. These studies should provide us with valuable results for the treatment of these patients, improve survival, reduce relapses, and obtain better obstetric outcomes. Thirteen clinical trials are registered in clinicaltrials.gov of fertility preservation in patients with early-stage endometrial cancer and atypical hyperplasia. Here, we present a short description of these studies; Clinical Trial NCT00788671: A phase II trial studying the efficacy of the levonorgestrel-releasing intrauterine system in treating patients with complex atypical hyperplasia or grade I endometrial cancer.Clinical Trial NCT02335203, comparing pre- and post-treatment glandular cellularity in women with complex atypical hyperplasia or grade 1–2 endometrial adenocarcinoma who are treated with intramuscular depot medroxyprogesterone acetate (DMPA) versus placebo injection prior to hysterectomy.Clinical Trial NCT02342730, a pilot clinical trial studying weight loss referral for healthier survivorship in obese stage I–II endometrial cancer patients or patients with atypical hyperplasia.Clinical Trial NCT02397083, a randomized phase II trial studying the efficacy of the levonorgestrel-releasing intrauterine system alone or with everolimus in patients with atypical hyperplasia or stage IA grade 1 endometrial cancer.Clinical Trial NCT02990728, studying the efficacy of LNG-IUS with or without metformin, as fertility-preserving treatment for grade 1 endometrioid adenocarcinoma of the endometrium.Clinical Trial NCT03042897, a pilot clinical trial studying exercise and diet intervention in promoting weight loss in obese patients with stage I endometrial cancer.Clinical Trial NCT03241914, a randomized study of the effectiveness of megestrol acetate plus LNG-IUS, aiming to demonstrate that it is not inferior to megestrol acetate alone for returning the endometrial tissue to a normal state in patients with early endometrial cancer.Clinical Trial NCT03463252, analyzing the effectiveness of LNG-IUS, in the fertility-sparing treatment of atypical endometrial hyperplasia and early endometrial carcinoma, including pathology response and pregnancy outcome.Clinical Trial NCT04008563 (Bi-FiERCE), a novel study that combines a surgical treatment (bariatric surgery) with the classic treatment of progestogens in patients with atypical hyperplasia and grade 1 cancer of the endometrium.Clinical Trial NCT04046185, a randomized controlled trial comparing programmed death-1 (PD-1) inhibitor combined with progesterone versus progesterone alone in the treatment of early stage endometrial cancer.Clinical Trial NCT04362046 (FETCH), evaluating the use of hysteroscopic resection in women diagnosed with atypical endometrial hyperplasia or grade I endometrial cancer who have not responded to hormone therapy.Recently, the feMMe-controlled trial was published, in which women with EC and AEH treated with LNG-IUS alone or plus metformin (M) or weight loss (WL) intervention. Thirty-five participants were randomized to observation, 36 to WL and 47 to M (10 patients were withdrawn). The results were promising: complete response rate was 82% for AEH and 43% for EC. In addition, the use of weight loss regimen plus LNG-IUS improved the treatment success, achieving an encouraging response rate of 67% . AnotherCurrently, only small retrospective case series including Grade 2 endometrioid endometrial cancer (EEC) for fertility preservation has been published. One reported a similar complete response rate and recurrence rate to Grade 1 EEC .The European Society of Gynecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) have published updates on endometrial cancer. To date, very few studies have been published on the preservation of fertility in stage IA Grade 2 endometrioid carcinoma without myometrial invasion, using MPA + LNG-IUS. The few performed were carried out by specialized gynecologists with a well-designed protocol and correct follow-up .Hwang et al.  publisheIn 2020, Falcone et al. published a multicenter project endorsed by the Gynecologic Cancer Inter-Group, for patients with G2 endometrioid EC. The study included 23 patients, of whom 74% received hysteroscopic resection plus progestin. After a median follow up of three years, 74% achieved a complete response with a recurrence rate of 41%. Only 58% attempted to conceive, achieving a live birth rate of 17%. The conclusion was that this approach seemed to be feasible, although the population sample was very limited .Lynch syndrome, or hereditary non-polyposis colon cancer  is an autosomal dominant hereditary syndrome with high penetrance. It is caused by the mutation of a mismatch repair gene, involved in DNA mismatch repair (MMR)—MLH1 (34% of cases), MSH2 (51%), MSH6 (49%) and PMS2 (24%) ,80.Women with an MSH6 mutation are at increased risk of endometrial cancer  .Lynch syndrome accounts for approximately 3% of all ECs, but this figure rises to 9% of ECs in women under the age of 50 years ,83,84,85Patients with Lynch syndrome have an increased risk of EC. In the general population the risk of EC is 2.5–3% , but in -The identification of susceptible patients from their personal and family histories. Amsterdam criteria (I and II)  have tra-The assessment of the reactive immunity for the mismatch repair genes  in all endometrial malignant tumors in women under 70 years with a family or personal history of tumors associated with Lynch syndrome, with simultaneous tumors in the ovary, or when the tumor has suspicious microscopic features  .-The performance of a genetic study in patients who meet all the Amsterdam criteria or any of the Bethesda criteria; as well as in patients with colorectal or endometrial cancer with evidence of DNA repair alteration or with a first or second degree relative with a known MRS mutation .To detect Lynch syndrome in patients, the following steps are recommended:There is no definitive scientific evidence of the impact of routine screening for endometrial carcinoma in patients diagnosed with Lynch syndrome. Due to the increased risk of endometrial cancer in this group and the associated morbidity and mortality, it is agreed that systematic screening is indicated. Based on expert recommendations, a transvaginal ultrasound and/or endometrial biopsy should be performed annually from the age of 30–35 years onward ,93.A reduction in the incidence of endometrial cancer has been observed associated with prophylactic hysterectomy and bilateral annexectomy. However, there is no scientific evidence that risk-reducing surgery is associated with a decrease in mortality from these causes. The main guidelines state that the possibility of prophylactic surgery, hysterectomy and bilateral annexectomy should be evaluated, once the wish to give birth has been fulfilled .Therapeutic management of endometrial cancer in patients with Lynch syndrome does not present any differences with respect to sporadic EC. There is no consensus on the conservative management of EC in Lynch syndrome patients. According to a European survey, Lynch syndrome is a contraindication for conservative management in half of the responders . HoweverThere is a consensus across the leading gynecologic oncology societies that fertility-sparing treatment is feasible and safe for young patients with G1 endometrioid EC limited to the endometrium. The use of progestins seems to achieve very good response rates. Combination treatments such as metformin or hysteroscopy resection following medical therapy may improve the recurrence rate. The molecular classification must be included to individualize the treatment. ARTs may shorten the time to conception.The mortality with this approach is very low, despite the very high rate of recurrence. The overall survival at 15-year follow up is around 90%. With the evidence provided by the published meta-analyses, we observed a complete response rate around 75% for oral progestin, and around 79% for LNG-IUS. The live birth rate was between 20–48%, depending on the treatment performed or the use of ART. The recurrence rate was close to 33% and was lower in studies that used LNG-IUS (11%) or hysteroscopic resection (14%).The addition of metformin to progestogens, hysteroscopic resection of AEH and EC associated with LNG-IUS or other treatments; weight reduction with bariatric surgery or other interventions should be studied in more detail. All these treatments, alone or in combination, are options for the future.In the absence of larger prospective studies, it is very important to consider overall health and fertility potential prior to recommending non-standard oncologic treatments. Further randomized controlled trials are now needed to offer stronger evidence.


CATCH-ON, the collaborative GWEP led by Rush University Medical Center, is working to create Age-Friendly Communities by assuring that health systems, community-based organizations, and older adults and families are educated about the 4Ms. For providers, CATCH-ON offers a monthly Learning Community that focuses on one of the 4Ms each quarter. Each session provides practical recommendations for 4Ms implementation and opportunities to share experiences in small groups. CATCH-ON also partnered with Community Catalyst, older adults, and caregivers to develop a 4Ms educational brochure. The brochure is available electronically and by paper to educate older adults and caregivers about the 4Ms and discussing them with their healthcare team. Additionally, CATCH-ON created 4M online modules for older adults and families. This session will explore the success and lessons learned in developing educational interventions for diverse audiences and how this approach strengthens Age-Friendly Communities.


Due to strict, nationwide, comprehensive COVID-19 protective measures, including home quarantine, all Chinese medical students began taking web-based classes beginning in the spring semester of 2020. Home quarantine, web-based classes, and the stress surrounding the COVID-19 pandemic may have triggered an increased incidence of mental health problems among medical students. Although there have been increasing amounts of literature on depression among medical students, studies focusing on positive psychological resources, such as resilience during the COVID-19 pandemic, still need to be expanded.This study aims to assess depression among medical students who are taking web-based classes during the COVID-19 pandemic and to investigate the role of coping styles as mediators between resilience and depression.A cross-sectional study of 666 medical students involving stratified sampling in Shenyang, Liaoning Province, China, was completed between March 20 and April 10, 2020. The participants responded to a self-administered, smartphone-based questionnaire, which included the Patient Health Questionnaire-9, Simplified Coping Style Questionnaire, and Ego Resilience 89 Scale. Hierarchical linear regression and structural equation modeling were used in this study.P=.013), how well students adapted to web-based classes (P<.001), their levels of resilience (P=.04), and their coping styles were independent predictors for depression (P<.001). Resilience and positive coping styles were negatively related to depression , and negative coping styles were positively related to depression (P<.001). The structural equation modeling analysis showed that the effect of resilience on depression was partially mediated by coping styles (P=.007).The prevalence of depression among the participants was 9.6% (64/666) in this study. The regression analysis revealed that grade  (In this study, it was found that the prevalence of depression was slightly low and coping styles mediated the association between resilience and depression among medical students during the COVID-19 pandemic. These findings have significant implications for future studies. Future studies and interventions should aim to improve resilience and promote positive coping styles. The COVID-19 pandemic has deeply affected peoples’ lives all over the world since its emergence in 2019. Both isolation and economic pressure have had a profound impact on the psychosocial environment in each affected country. The pandemic has also increased the public’s susceptibility to detrimental psychological consequences .School lockdowns were implemented in many countries . In ordeDepression—a mood disorder defined by sadness, inactivity, the loss of appetite or overeating, and difficulty in concentrating—can result in the reduced ability to perform daily activities among some people. Depression is one of the most often identified health issues among college undergraduates ,8 and isThe cognitive-behavioral model of health anxiety  suggestsThere are many recent, positive psychology ,23 studiAccording to the transactional stress model theory, the process of coping plays a significant role in individuals’ responses to stress . Coping This study assessed the prevalence of depression among medical students and determined whether coping styles play a mediating role in the relationship between resilience and depression among medical students during the COVID-19 pandemic. This study examined the following three hypotheses: (1) higher levels of resilience predict lower depression scores; (2) coping exerts a positive effect on relieving depression; and (3) coping styles mediate the relationship between resilience and depression.A cross-sectional study involving stratified sampling was carried out by conducting a self-administered questionnaire on Wenjuanxing—a smartphone- and web-based questionnaire platform—between March 20 and April 10, 2020. Wenjuanxing is a widely used, open, web-based questionnaire platform that was developed by Changsha Ranxing Information and Technology Limited Company. The free and self-design version was used in this study. The validity and reliability of the questionnaire that we designed and used in this study were examined.Medical students who were home-quarantined in their first, second, or third year at China Medical University were eligible for this study. In total, 8 classes from each grade in which the medical students were in training were randomly selected. The medical students from 24 classes in their first, second, or third year at China Medical University were selected as the participants and finished the questionnaire. Of the total 720 medical students who were recruited in this study, 666 participants responded completely to the questionnaire, resulting in a valid response rate of 92.5% (666/720).All participants were fully informed of the study protocol and provided informed consent prior to taking the web-based questionnaire. Participation was voluntary and anonymous. The study protocol was approved by the Ethics Committee of China Medical University.Demographic information, including grade , gender, age (<20 years and ≥20 years), fathers’ education , mothers’ education , monthly income (≤RMB 5000 [US $778.30] and >RMB 5000 [US $778.30]), major , and whether students adapted to web-based classes (yes or no), was collected.Depression was measured with the Patient Health Questionnaire-9 (PHQ-9), which is commonly used for the measurement of depression based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, is comparably sensitive and specific, and includes 9 items . A scoreCoping styles were assessed with the Simplified Coping Style Questionnaire, which included 20 items using a Likert scale of 0 (never) to 3 (frequently). In this study, the Cronbach α coefficient of the Simplified Coping Style Questionnaire was .862.Resilience was measured with the Ego Resilience 89 Scale, which has good internal reliability  as well t tests (two-tailed) and one-way analysis of variance tests, and a two-tailed P value of less than .05 considered statistically significant.SPSS 17.0 (IBM Corporation) and AMOS  24.0 (IBM Corporation) were used for statistical analyses in the present study. The comparison of differences among classified groups was conducted with In order to examine the incremental variance of any given set of independent variables and to assess the mediating role of coping styles in the association between resilience and depression, hierarchical linear regression analysis was used. Depression was used as the dependent variable. Resilience and coping styles were used as the independent variables. The variables were entered into models via the following step-by-step process: in step 1, the demographic characteristics of the medical students were entered; in step 2, resilience was entered; and in step 3, coping styles were entered. The following criteria for establishing the mediating effects, according to Baron and Kenny  in theirTo prove that coping styles played a mediating role in the relationship between resilience and depression, structural equation modeling was used. Bootstrapping strategies were used to examine the mediating role (a×b product) of coping styles in the relationship between resilience and depression. The bootstrap estimate was based on 5000 bootstrap samples, and the bias-corrected and accelerated (BCa) 95% CI for each a×b product was examined. The goodness of fit was determined by the following: a chi-square to df ratio of <5, a goodness-of-fit index (GFI) of >0.90, a comparative fit index (CFI) of >0.90, a root mean square error of approximation (RMSEA) of <0.08, and a Tucker-Lewis Index (TLI) of >0.90.The study protocol conformed to the ethical standards of and was approved by the Ethic Committee of China Medical University. All participants gave their consent after being informed of the purpose and procedure of the study via a web-based platform. The confidentiality and anonymity of all participants' collected information were ensured.The informed consent of every participant was acquired before the launch of the procedures of this research.P=.045). Up to 88.9% (592/666) of the participants were adapting to web-based classes, while 11.1% (74/666) were not. The depression scores among the students who were not adapting to web-based classes were significantly higher than those among the students who were adapting to web-based classes (P<.001).The demographic characteristics and their respective mean depression scores are shown in P<.001) and positive coping styles (P<.001), while depression was significantly and positively associated with negative coping styles among medical students (P<.001).The correlations between depression and the continuous variables are shown in P=.013), resilience (P=.04), positive coping styles (P<.001), and negative coping styles (P<.001) were significant predictors for depression. Grade, resilience, and positive coping styles were negatively associated with depression, while negative coping styles were positively associated with depression.The linear regression models of depression among medical students are presented in P<.001) before coping styles were entered as a mediator. The model revealed that resilience had a significant negative effect on depression (P<.001), and this model had good model fit indices , which confirmed coping styles' partial mediating role in the association between resilience and depression. This model yielded a good model fit . According to the BCa bootstrap test, coping styles played a significant mediating role in the association between resilience and depression , which proved that coping styles had a significant role as a mediator between resilience and depression.As far as we know, this study presents the first attempt to investigate the relationship among resilience, coping styles, and depression among Chinese medical students in the context of web-based classes during the COVID-19 pandemic. In this study, 64 out of the 666 (9.6%) participants reported depression, which was slightly higher than the depression prevalence of 9% in a study of home-quarantined Chinese college students that was conducted during the COVID-19 pandemic  but loweP=.013) and whether students adapted to web-based classes (P<.001) had significant impacts on depression. With the national requirement of “suspending classes without suspension of learning” in China during the COVID-19 pandemic, web-based studying at home provided the only feasible method for keeping up with the learning schedule. The results in this study showed that the 11.1% (74/666) of participants who did not adapt to web-based classes had significantly higher depression scores (P<.001). This may be because the students who failed to adapt to web-based classes were more accustomed to face-to-face instruction and web-based classes added to their stress, which could result in increased levels of depression.In this study, grade , which is in line with previous studies [The findings from this study showed that coping styles had a significant effect on relieving depression  and coping styles (P<.001) were significantly related to depression. Positive coping styles played an essential role in decreasing depression levels among medical students, while negative coping styles were positively related to depression. It was also found that coping styles mediated the association between resilience and depression. This study indicates that interventions that aim to enable the development of positive coping styles among individuals and improve their resilience are of great practical importance to decreasing depression levels among medical students while they are taking web-based classes during the large-scale COVID-19 pandemic.This study found that Chinese medical students in web-based classes experienced slightly low levels of depression during the COVID-19 pandemic. Resilience (