Nirmatrelvir/Ritonavir for hemodialysis patients with COVID-19.

Background: Hemodialysis patients have a high risk of severe/critical COVID-19 and related high mortality, but nirmatrelvir/ritonavir is not recommended for hemodialysis patients with COVID-19 infection because of lack of evidence of safety. Objectives: Our study aims to evaluate the minimum plasma concentration (Cmin) of nirmatrelvir and its safety of different doses of nirmatrelvir/ritonavir in hemodialysis patients with mild COVID-19. Method: This was a prospective, two step, nonrandomized, open-label study. Participants were treated with nirmatrelvir 150 mg or 300 mg once a day (another 75 mg or 150 mg supplied after hemodialysis) and ritonavir 100 mg twice daily for 5 days, respectively. The primary outcome was the safety of nirmatrelvir/ritonavir, including the Cmin of nirmatrelvir and the number of adverse events (AE). The secondary outcome was the time of viral elimination in hemodialysis patients. Results: Adverse events were happened in 3 and 7 participants in the step 1 and step 2 group, respectively (p = 0.025). Among them, 2 and 6 participants were identified as drug-related adverse events (p = 0.054). No SAE or liver function damage happened. The Cmin of nirmatrelvir in step 1 and step 2 group were 5,294.65 ± 2,370.59 ng/mL and 7,675.67 ± 2,745.22 ng/mL (p = 0.125). The Cmin of the control group was 2,274.10 ± 1,347.25 ng/mL (p = 0.001 compared to step 2 and p = 0.059 compared to step 1). Compared to hemodialysis patients without nirmatrelvir/ritonavir, there were no statistical differences in overall viral elimination time (p = 0.232). Conclusion: In our study, two doses of nirmatrelvir/ritonavir appeared to be excessive for hemodialysis patients. Although all of the patients tolerated 5-day administration, nearly half of the patients experienced drug-related adverse events. In addition, the medication group did not show a significant advantage in the time of viral elimination.

Mortality following mechanical thrombectomy for ischemic stroke in patients with COVID-19.

OBJECTIVES: Multiple prior studies have shown a relationship between COVID-19 and strokes; further, COVID-19 has been shown to influence both time-to-thrombectomy and overall thrombectomy rates. Using large-scale, recently released national data, we assessed the association between COVID-19 diagnosis and patient outcomes following mechanical thrombectomy. MATERIALS AND METHODS: Patients in this study were identified from the 2020 National Inpatient Sample. All patients with arterial strokes undergoing mechanical thrombectomy were identified using ICD-10 coding criteria. Patients were further stratified by COVID diagnosis (positive vs. negative). Other covariates, including patient/hospital demographics, disease severity, and comorbidities were collected. Multivariable analysis was used to determine the independent effect of COVID-19 on in-hospital mortality and unfavorable discharge. RESULTS: 5078 patients were identified in this study; 166 (3.3%) were COVID-19 positive. COVID-19 patients had a significantly higher mortality rate (30.1% vs. 12.4%, p < 0.001). When controlling for patient/hospital characteristics, APR-DRG disease severity, and Elixhauser Comorbidity Index, COVID-19 was an independent predictor of increased mortality (OR 1.13, p = 0.002). COVID-19 was not significantly related to discharge disposition (p = 0.480). Older age and increased APR-DRG disease severity were also correlated with increase morality. CONCLUSIONS: Overall, this study indicates that COVID-19 is a predictor of mortality among mechanical thrombectomy. This finding is likely multifactorial but may be related to multisystem inflammation, hypercoagulability, and re-occlusion seen in COVID-19 patients. Further research would be needed to clarify these relationships.

Adaptive immune dysfunction in patients with COVID-19 and impaired kidney function during the omicron surge.

BACKGROUND: Little is known about the characteristics of lymphocyte subsets and the association with patient outcomes in COVID-19 with and without impaired kidney function. METHODS: Lymphocyte subsets were compared in COVID-19 patients with or without kidney dysfunction. The primary outcome was a composite of all-cause mortality or intensive care unit admission. Secondary outcomes included duration of viral shedding, length of hospital stay, and acute kidney injury. RESULTS: Lymphocyte subset cell counts demonstrated the lowest in patients with severe/critical COVID-19 and kidney dysfunction. Among all lymphocyte subset parameters, Th cell count was the most significant indicator for outcomes. ROC of the combined model of Th cell count and eGFR presented better predictive value than that of the other parameters. Th cell count <394.5 cells/µl and eGFR <87.5 ml/min/1·73m2 were independently associated with poor outcomes. The propensity score matching analysis revealed consistent results. CONCLUSIONS: Reduced Th cell count and eGFR may be applied as promising predictive indicators for identifying COVID-19 patients with high risk and poor outcomes.

Serum miR-21 and miR-148b levels in patients with chronic hepatitis B and their predictive value for liver tissue inflammation grading and fibrosis staging

Objective: The aim of this study was to explore the predictive value of serum microRNAs (miR)-21 and miR-148b for liver histopathological inflammation grading and fibrosis staging in patients with chronic hepatitis B (CHB).

Association of COVID-19 patient's condition with fasting blood glucose and body mass index: A retrospective study.

BACKGROUND: The COVID-19 pandemic broke out in 2019 and rapidly spread across the globe. Most of the severe and dead cases are middle-aged and elderly patients with chronic systemic diseases. OBJECTIVE: This study aimed to assess the association between fasting blood glucose (FPG) and body mass index (BMI) levels in patients with coronavirus disease 2019 (COVID-19) under different conditions. METHODS: Experimental-related information (age, gender, BMI, and FPG on the second day of admission) from 86 COVID-19 cases (47 males and 39 females) with an average age of (39 ± 17) years was collected in April and November 2020. These cases were divided into three groups according to the most severe classification of each case determined by the clinical early warning indicators of severe-critically illness, the degree of progression, and the treatment plan shown in the diagnosis and treatment plan of COVID-19 pneumonia. Statistical models were used to analyze the differences in the levels of FPG and BMI, age, and gender among the three groups. RESULTS: 1. Experimental group: 21 patients with asymptomatic or and mild symptoms (group A), 45 patients with common non-progression (group B), and 20 patients with common progression and severe symptoms (group C). 2. The age differences among the three groups were statistically significant and elderly patients had a higher risk of severe disease (t= 4.1404, 3.3933, 9.2123, P= 0.0001, 0.0012, 0.0000). There was a higher proportion of females than males in the normal progression and severe disease cases (χ2= 5.512, P= 0.019). 3. The level of FPG was significantly higher in group C than in group A (t= 3.1655, P= 0.0030) and B (t= 2.0212, P= 0.0475). The number of diabetes or IFG in group C was significantly higher than in group A (χ2= 5.979, P= 0.014) and group B (χ2= 6.088, P= 0.014). 4. BMI was significantly higher in group C than in groups A (t= 3.8839, P= 0.0004) and B (t= 3.8188, P= 0.0003). The number of overweight or obese patients in group C was significantly higher than in groups A (χ2= 8.838, P= 0.003) and B (χ2= 10.794, P= 0.001). 5. Patients' age, gender, and FPG were independent risk factors for COVID-19 disease progression (ß= 0.380, 0.191, 0.186; P= 0.000, 0.034, 0.045). CONCLUSION: The levels of FPG and BMI were significantly increased in the population with common progressive and severe COVID-19. FPG and age are independent risk factors for the progression of COVID-19.

A survey of health status of healthcare providers in a square cabin hospital during the new corona omicron outbreak: A cross-sectional study

Background The coronavirus omicron variant outbroke in early 2022 in Shanghai. Although previous studies indicated that long working hours in a square cabin hospital might increase the risk of mental health among frontline healthcare providers, few studies have investigated whether the mental health risk could be reduced among well-trained professionals following the new guidelines. Objective This study aimed to investigate the health situation of frontline healthcare providers in Shanghai square cabin during the omicron variant circulation. Methods An online survey was used to evaluate those healthcare providers working in the square cabin hospitals from March 1, 2022, to May 31, 2022. The first online survey was conducted and emailed to the health providers on April 1. The second survey was conducted and sent to the nonrespondents on May 31. Overall, 142 frontline healthcare providers completed the online survey. Their mental health was assessed by the Insomnia Severity Index Scale, the Generalized Anxiety Disorder Scale, the Patient Health Questionnaire-9, and the Psychological Resilience Scale. We estimated multiple clinical systems and identified factors associated with those symptoms among participants. Multivariable logistic regression models were used to assess the risk factors of these symptoms. Results Overall, 66.20%, 45.07%, and 27.46% of frontline healthcare providers in Shanghai City reported symptoms of insomnia, depression, and anxiety, respectively. In addition, the most common symptoms included dry eyes (57.75%), lumbar muscle strain (47.18%), dry mouth (35.92%), itching (31.69%), headache (29.58%), and sore throat (28.87%) among the frontline healthcare providers. There was no statistical difference in symptoms by gender, age, personnel category, or job position (p > 0.05). Conclusion In the case of an unexpected pandemic, the mental health of healthcare providers is not optimistic. This situation still exists more than 2 years after the global outbreak of the COVID-19 pandemic. Therefore, the physical and mental health of long-term healthcare providers working in a square cabin hospital still needs monitoring.

Detection of Neutralizing Anti-Type 1 Interferon Autoantibodies.

Autoantibodies (autoAbs) that neutralize type 1 interferons (T1IFNs) are a major risk factor associated with developing critical COVID-19 disease and are most commonly found in individuals over age 70 and in patients with genetic or acquired thymic defects. Swift identification of autoAb-positive individuals may allow targeted interventions to prevent critical COVID-19 disease. Herein, we provide a workflow and protocols aimed at rapidly identifying individuals who are autoAb positive from a large cohort. Basic Protocol 1 describes a multiplex particle-based assay to screen large cohorts of individuals for binding levels of anti-T1IFN autoAbs, and Basic Protocol 2 describes a functional assay to test if autoAbs in patient plasma can block T1IFN-induced JAK/STAT signaling. © Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Basic Protocol 1: Multiplex particle-based bead assay to screen for binding levels of anti-type 1 interferon autoantibodies Alternate Protocol: Multiplex particle-based bead assay to screen for binding levels of anti-type 1 interferon immunoglobulin subtypes and isotypes Support Protocol: Coupling type 1 interferons (IFN-α, IFN-ß, and IFN-ω) to magnetic beads Basic Protocol 2: pSTAT1 functional assay to test for neutralization activity of anti-type 1 interferon autoantibodies.

The specter of empty countrysides and wetlands—Impact of hunting take on birds in Indo‐Burma

Hunting for the wild meat trade, medicines and other human uses has decimated Indo‐Burma's vertebrate biota and has led to widespread defaunation. Yet, there is surprisingly little data on how hunting impacts wild bird assemblages in different landscapes here. Based on concurrent snapshot surveys of bird hunting, food markets and hunting attitudes across six Indo‐Burma countries, we found that hunting threatens species not only in forested landscapes but also wetlands and farmlands such as orchards and paddy fields—ecosystems overlooked by past studies, with at least 47 species associated with wetlands and agricultural lands identified from market surveys across the region. High rates of mortality are suffered when hunting tools such as nets are used to exclude perceived bird pests in both aquaculture and agricultural landscapes, with over 300 individual carcasses of at least 29 identifiable species detected in one aquaculture landscape sampled in Thailand. We warn that the potentially unsustainable trapping of species for consumption and trade in Indo‐Burma, coupled with high incidental mortalities, could decimate the populations of erstwhile common and/or legally unprotected species. There is an urgent need for stronger regulatory oversight on the hunting take of wild birds and the use of hunting tools such as nets. Alongside this, conservation practitioners need to better engage with rural communities to address unsustainable hunting practices, especially outside of protected areas.

Improving ABCDEF Bundle Compliance and Clinical Outcomes in the ICU: Randomized Control Trial to Assess the Impact of Performance Measurement, Feedback, and Data Literacy Training

OBJECTIVES: Describe the effects of data literacy training and continuous performance reports on ICU staff compliance with the 6-element ICU quality bundle approach known as the ABCDEF (A–F) bundle and patient outcomes. DESIGN: Stepped-wedge cluster randomized trial conducted during an institutional A–F bundle implementation program. SETTING: Single-center study conducted in eight adult ICUs. PATIENTS: Adult patients admitted for at least 24 hours, not undergoing active withdrawal of life support or palliative care. INTERVENTIONS: Four ICUs in the intervention group received bundle-related staff education, data literacy training, and weekly bundle performance reports during the 12-month study period. The four ICUs in the nonintervention group received none of these interventions. Bundle compliance and patient outcomes were tracked, including ICU and hospital mortality, transfer and discharge, discharge disposition, mechanical ventilation, and ICU delirium. MEASUREMENT AND RESULTS: In the intervention group, staff education alone increased bundle compliance from 9% to 16% (p < 0.0001);data literacy training further increased compliance from 16% to 21% (p = 0.03). This improvement was sustained throughout the study period including the onset of the COVID-19 pandemic and was greater than improvement in the nonintervention group (p < 0.001). Full A–F bundle compliance was associated with a lower likelihood of next-day ICU and hospital mortality, discharge to a facility other than home, and was associated with a higher likelihood of next-day extubation in patients. Next-day ICU and hospital discharge likelihood decreased, and delirium frequency was not affected. CONCLUSIONS: This is the first study demonstrating that the combination of staff education, data literacy training, and access to performance data improves A–F bundle compliance, sustains performance, and improves ICU patient outcomes (ICU and hospital mortality, mechanical ventilation duration, and home discharge rates). In contrast to previous studies, increased bundle compliance did not hasten ICU or hospital discharges or reduce delirium frequency in patients.

Restaurant proactive philanthropic activities and customer loyalty: a scenario-based study during the COVID-19 pandemic period

PurposeThis study aims to (1) examine the effect of customer awareness of restaurant philanthropic activities on customer loyalty;(2) investigate the mediating roles of customer social benevolence trust, perceived restaurant reputation and affective commitment on the relationship between their awareness of restaurant philanthropic activities and customer loyalty;and (3) test the path effect differences between the directed and general philanthropic activities during the COVID-19 pandemic period.Design/methodology/approachThis study used online scenario-based surveys to collect data. Based on 293 useable surveys, partial least squares structural equation modeling was applied for data analysis.FindingsThis study finds that customer awareness of restaurant philanthropic activities positively relates to customer loyalty. Moreover, customer social benevolence trust, perceived restaurant reputation and affective commitment have positive mediating effects on the relationship between their awareness of restaurant philanthropic activities and customer loyalty. There is no significant path effect difference between the directed and general philanthropic activities.Practical implicationsThis study suggests that restaurant decision-makers should conduct either directed or general philanthropic activities as a marketing tool to sustain customers during the COVID-19 recovery.Originality/valueThis study is the first study that discusses the marketing role of corporate philanthropy in the restaurant industry during the COVID-19 pandemic and stresses the importance of proactive strategic donations that helps restaurants' recovery.

Quo Vadis? Carbon Peak and Emission Network for China in the Post-Pandemic Era (preprint)

China’s carbon peak greatly impacts global climate targets. Limited studies have comprehensively analyzed the influence of the COVID-19 pandemic, changing emission network, and recent carbon intensity (CI) reduction on the carbon peak and the corresponding mitigation implications. Using a unique dataset at different levels, we project China’s CO2 emission by 2035 and analyze the time, volume, driver patterns, complex emission network, and policy implications of China’s carbon peak in the post- pandemic era. We develop an ensemble time-series model with machine learning approaches as the projection benchmark, and show that China’s carbon peak will be achieved by 2021–2026 with > 80% probability. Most Chinese cities and counties have not achieved carbon peaks response to the priority-peak policy and the current implementation of CI reduction should thus be strengthened. While there is a "trade off" between the application of carbon emission reduction technology and economic recovery in the post-pandemic era, a close cooperation of interprovincial CO2 emission is also warranted.

Development and evaluation of inhalable composite niclosamide-lysozyme particles: a broad-spectrum, patient-adaptable treatment for coronavirus infections and sequalae

Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, administration of the currently available oral formulation results in systemic drug levels that are too low for the inhibition of SARS-CoV-2. We hypothesized that the co-formulation of NIC with an endogenous protein, human lysozyme (hLYS), could enable the direct aerosol delivery of the drug to the respiratory tract as an alternative to oral delivery, thereby effectively treating COVID-19 by targeting the primary site of SARS-CoV-2 acquisition and spread. To test this hypothesis, we engineered and optimized composite particles containing NIC and hLYS suitable for delivery to the upper and lower airways via dry powder inhaler, nebulizer, and nasal spray. The novel formulation demonstrates potent in vitro and in vivo activity against two coronavirus strains, MERS-CoV and SARS-CoV-2, and may offer protection against methicillin-resistance staphylococcus aureus pneumonia and inflammatory lung damage occurring secondary to SARS-CoV-2 infections. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure rapid clinical development and wide-spread utilization.

Exploring the Mechanism of Coagulation Dysfunction in a Sepsis Model though Gene Expression Profiles (preprint)

Objective: Sepsis is a life-threatening condition, and the mechanism of coagulation dysfunction in sepsis remains unknown. We aimed to investigate the mechanism of coagulation dysfunction in sepsis. Methods: . Standard methods were used to establish the sepsis models and generate gene expression profiles. Bioinformatics analysis was carried out by GO and KEGG enrichment analysis, construction of PPIs and screening of seed genes. Finally, seed genes were used to rebuild the disease-related pathways. Results: . Our experiments revealed an inflammatory response and coagulation dysfunction in both animal and cell models. After determining the DEGs, GO and KEGG functional analysis showed that there is a significant correlation between the inflammatory response and DNA damage. PPI network analysis screened 9 seed genes related to cell mitosis and platelet-derived growth factor receptor signaling pathways. Some of the seed genes were relevant to COVID-19. Conclusions: . This study explored the molecular mechanism of coagulation dysfunction in sepsis models by bioinformatics analysis. This may have guiding significance in reducing the risk of complications in patients with sepsis and improving the effectiveness of treatment.

Trends in Trauma Admissions During the COVID-19 Pandemic in Los Angeles County, California.

Importance: Describing the changes in trauma volume and injury patterns during the course of the coronavirus disease 2019 (COVID-19) pandemic could help to inform policy development and hospital resource planning. Objective: To examine trends in trauma admissions throughout Los Angeles County (LAC) during the pandemic. Design, Setting, and Participants: In this cohort study, all trauma admissions to the 15 verified level 1 and level 2 trauma centers in LAC from January 1 to June 7, 2020 were reviewed. All trauma admissions from the same period in 2019 were used as historical control. For overall admissions, the study period was divided into 3 intervals based on daily admission trend analysis (January 1 through February 28, March 1 through April 9, April 10 through June 7). For the blunt trauma subgroup analysis, the study period was divided into 3 similar intervals (January 1 through February 27, February 28 through April 5, April 6 through June 7). Exposures: COVID-19 pandemic. Main Outcomes and Measures: Trends in trauma admission volume and injury patterns. Results: A total of 6777 patients in 2020 and 6937 in 2019 met inclusion criteria. Of those admitted in 2020, the median (interquartile range) age was 42 (28-61) years and 5100 (75.3%) were men. Mechanisms of injury were significantly different between the 2 years, with a higher incidence of penetrating trauma and fewer blunt injuries in 2020 compared with 2019 (penetrating: 1065 [15.7%] vs 1065 [15.4%]; blunt: 5309 [78.3%] vs 5528 [79.7%]). Overall admissions by interval in 2020 were 2681, 1684, and 2412, whereas in 2019 they were 2462, 1862, and 2613, respectively. There was a significant increase in overall admissions per week during the first interval (incidence rate ratio [IRR], 1.02; 95% CI, 1.002-1.04; P = .03) followed by a decrease in the second interval (IRR, 0.92; 95% CI, 0.90-0.94; P < .001) and, finally, an increase in the third interval (IRR, 1.05; CI, 1.03-1.07; P < .001). On subgroup analysis, blunt admissions followed a similar pattern to overall admissions, while penetrating admissions increased throughout the study period. Conclusions and Relevance: In this study, trauma centers throughout LAC experienced a significant change in injury patterns and admission trends during the COVID-19 pandemic. A transient decrease in volume was followed by a quick return to baseline levels. Trauma centers should prioritize maintaining access, capacity, and functionality during pandemics and other national emergencies.

COVID-19 impacts, coping strategies, and management reflection: A lodging industry case.

The COVID-19 pandemic has hit the global tourism and hospitality industry with drastic results. Hotels have been experiencing unprecedented challenges, leaving many to temporarily or permanently closed. Employing a case study approach supported by both quantitative and qualitative analysis, this study examined how two hotels in Oklahoma City had coped with challenges presented by the COVID-19 pandemic, from day to day operations, health and safety measures to marketing, human resources and cost-saving strategies. The study contributes to the tourism crisis and disaster literature by providing micro-level coping strategies, a literature gap that needs to be addressed, particularly under the current pandemic.

Comparison of patients hospitalized with COVID-19, H7N9 and H1N1.

BACKGROUND: There is an urgent need to better understand the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for that the coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. This paper was to differentiate COVID-19 from other respiratory infectious diseases such as avian-origin influenza A (H7N9) and influenza A (H1N1) virus infections. METHODS: We included patients who had been hospitalized with laboratory-confirmed infection by SARS-CoV-2 (n = 83), H7N9 (n = 36), H1N1 (n = 44) viruses. Clinical presentation, chest CT features, and progression of patients were compared. We used the Logistic regression model to explore the possible risk factors. RESULTS: Both COVID-19 and H7N9 patients had a longer duration of hospitalization than H1N1 patients (P < 0.01), a higher complication rate, and more severe cases than H1N1 patients. H7N9 patients had higher hospitalization-fatality ratio than COVID-19 patients (P = 0.01). H7N9 patients had similar patterns of lymphopenia, neutrophilia, elevated alanine aminotransferase, C-reactive protein, lactate dehydrogenase, and those seen in H1N1 patients, which were all significantly different from patients with COVID-19 (P < 0.01). Either H7N9 or H1N1 patients had more obvious symptoms, like fever, fatigue, yellow sputum, and myalgia than COVID-19 patients (P < 0.01). The mean duration of viral shedding was 9.5 days for SARS-CoV-2 vs 9.9 days for H7N9 (P = 0.78). For severe cases, the meantime from illness onset to severity was 8.0 days for COVID-19 vs 5.2 days for H7N9 (P < 0.01), the comorbidity of chronic heart disease was more common in the COVID-19 patients than H7N9 (P = 0.02). Multivariate analysis showed that chronic heart disease was a possible risk factor (OR > 1) for COVID-19, compared with H1N1 and H7N9. CONCLUSIONS: The proportion of severe cases were higher for H7N9 and SARS-CoV-2 infections, compared with H1N1. The meantime from illness onset to severity was shorter for H7N9. Chronic heart disease was a possible risk factor for COVID-19.The comparison may provide the rationale for strategies of isolation and treatment of infected patients in the future.

Clinical Time Features and Chest Imaging of 85 Patients With COVID-19 in Zhuhai, China.

Background: An outbreak of SARS-CoV-2 infections began in Wuhan, China, and quickly spread to the entire country. We sought to delineate the time features of clinical symptoms, virological conversion, and chest radiological abnormalities in individuals infected with this virus in Zhuhai, China. Methods: In this retrospective study, we assessed 85 confirmed cases of COVID-19 in the Fifth Hospital of Sun Yat-sen University, Zhuhai, from the 17th of January to the 11th of February 2020. Outcomes were followed up until the 24th of February 2020. Results: The median age of the 85 patients with COVID-19 was 43 years (range, 1-80); 56.5% (48/85) were female. The median time from the last known contact to the first SARS-CoV-2 positive test result was 8 days (0-18). The time to throat swab negativity for SARS-CoV-2 ranged from 5 to 36 days after illness onset. Patients with abnormal chest imaging findings on admission were older than those with normal imaging findings (median age, 50 [3-80] vs. 37 [1-69], P = 0.031). Among patients with lung changes on admission, the risk of lesions was 13.8 times greater in the left lower lobe than in the right middle lobe. Most lung lesions appeared within 2 weeks of onset (median 4-5 days). The overall rates of lesions in the right upper/middle/lower lobe and left upper/lower lobe were 47.1, 30.6, 62.4% as well as 49.4 and 63.5%, respectively. Conclusions: The incubation period of SARS-CoV-2 may be longer than 14 days; thus, medical surveillance after contact is required for longer than this. The predominant sites of lung lesions are both lower lungs, whereas the lowest risk region is the right middle lobe.