Prevalence of hyperuricemia was 12.5%. The eGFR-adjusted multivariate analysis showed that relative to patients with GGT ≤ 50, those with GGT between 51 and 300 U/L and those with GGT > 300 U/L were 4.31 (95% CI 1.62–11.46) and 10.3 (95% CI 3.50–29.90) times more likely to have hyperuricemia, respectively. Our data shows that hyperuricemia in the context of AUD is strongly associated with serum GGT levels and suggest an increased cardio-metabolic risk in this population.Excessive alcohol consumption leads to overproduction of urates and renal function plays a critical role in serum uric acid levels. We aimed to assess associations of hyperuricemia in patients with alcohol use disorder (AUD) and comparable Glomerular Filtration Rate (GFR). A total of 686 patients undergoing treatment for AUD between 2013 and 2017 were eligible (77% men); age at admission was 47 years , age of onset of alcohol consumption was 16 years  and the amount of alcohol consumed was 160 g/day . Body Mass Index was 24.7 kg/m The kidney is responsible for removing the majority (> 70%) of urates produced daily2. Excessive alcohol consumption, obesity, metabolic syndrome (MetS) and food products with a high concentration of purines or fructose have been associated with hyperuricemia3.Uric acid is a heterocyclic organic compound synthesized primarily in the liver and small intestine and the final product of purine catabolism. Other than purines obtained from food products, the primary endogenous source of urates is nucleic acids, specially adenine and guanine5. There are no universally accepted cut-off levels of serum uric acid (SUA) although serum concentrations from 5.0 to 7.5 mg/dL, depending on sex, are considered high. More than two-thirds of patients with hyperuricemia remain clinically asymptomatic, although the risk of developing gout is directly related to SUA levels6.The estimated prevalence of hyperuricemia in the general population is around 5% and it seems to be much higher in hospitalized patients7.The mechanisms explaining the pathophysiology of hyperuricemia includes the excessive urate production and the reduced renal and extra-renal excretion. The under-excretion of urates is the most frequent etiology (90% of cases) of hyperuricemia and it may be classified into primary conditions characterized by a decrease in the tubular secretion of urates, or into secondary conditions due to renal failure or other causes such as diabetes, alcoholic ketosis and lactic acidosis9.With respect to the role of ethanol in the SUA levels, excessive alcohol consumption accelerates adenosine triphosphate degradation in the liver and increases lactic acid levels in blood during the degradation of ethanol. Ethanol also increases the plasma concentration and decreases the urinary excretion of purine bases (i.e. hypoxanthine and xanthine) via the acceleration of adenine nucleotide degradation and the possible inhibition of the xanthine dehydrogenase activity. In addition, chronic alcohol consumption might diminish the urinary excretion of uric acid due to dehydration and ketoacidosis11. In addition, hyperuricemia may increase the risk of hepatic steatosis and gluconeogenesis, which contribute to MetS12. In parallel, patients with alcohol use disorder (AUD) may have a higher risk of cardiovascular risk factors and it is estimated that up to 20% of individuals with excessive alcohol consumption have MetS14.Hyperuricemia has been associated with an increased risk of cardiometabolic and renal disease15. However, associations of alcoholic beverages and SUA may be due to the effect of non-alcoholic components of beverages ; these components of alcoholic beverages may play a role in the variation of SUA levels16.Studies involving moderate alcohol drinkers have shown that SUA levels increase proportionally to the amount of alcohol consumed and that this increase is more pronounced among individuals drinking beer or distillates19. However, few studies have taken into account the role of GFR and impaired renal function in SUA levels which may affect prevalence and associations of hyperuricemia. The kidney has been recognized as a main regulator of SUA and renal urate excretion is determined by the balance of the reabsortion and secretion of urates2.It should be noted that the majority of studies on SUA and alcohol consumption have focused on hospitalized patients with acute, concurrent illness  or in the general populationWe hypothesize that the risk of hyperuricemia in the context of excessive alcohol consumption is multifactorial and related to multiple health outcomes which may have implications for clinical practice. We aimed to characterize associations of hyperuricemia in AUD patients with comparable GFR.This was a cross-sectional study in AUD patients consecutively admitted for detoxification in two hospital units in metropolitan Barcelona, Spain: Hospital Universitari de Bellvitge in L’Hospitalet de Llobregat and Hospital Universitari Germans Trias i Pujol in Badalona. All patients were consecutively admitted between January 2013 and November 2017; patients were referred to the Addiction Unit by primary care physicians and specialists in addiction medicine at outpatient clinics.20. Information was collected on socio-demographic variables . On admission day, patients underwent an interview including questions on alcohol consumption such as daily quantity and type of alcohol  and age at onset of alcohol use. Alcohol consumption was quantified in grams of ethanol per day. Current use of other substances  was ascertained by urine detection at admission. Anthropometric data (height and weight) were also obtained.All patients received a diagnosis of alcohol use disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Ed (DSM-5)Peripheral blood samples for determining biochemical and hematological parameters were collected the second day of admission after overnight fasting. Blood was collected in heparin plasma tubes and transferred to the laboratories. Hematological parameters , platelet count, leucocytes, and lymphocytes) and erythrocyte sedimentation rate (ESR) were measured using automated hematological profile analyzers; biochemical parameters  were measured with standard enzymatic methods using multichannel automatic analyzers; specifically, the enzymatic colorimetric method was used to assess the SUA level. Overall inter- and intra-assay variability was 3.6–12.4%. The clinical chemistry and hematology laboratories of both hospitals complied with UNE-EN-ISO9001:2015 standards which accredited them in their respective areas.Pharmacological treatment during admission included benzodiazepines, vitamin B complex, and other pharmacotherapy depending on medical co-morbidities, and severity of alcohol withdrawal.22.On average, the length of stay was 7 days, and at discharge, patients were advised to attend follow-up visits at the outpatient clinic. Other details regarding admission for the treatment of AUD can be found elsewhereA total of 739 patients were admitted during the study period but patients treated with diuretics (n = 36), uricosuric agents (n = 12), or both (n = 5) were excluded yielding 686 for analysis presented here. The established cut-off value for hyperuricemia was > 7.2 mg/dL in men and > 6 mg/dL in women based on the reference values provided by the hospital laboratories.Renal function was assessed by the estimated glomerular filtration rate (eGFR), calculated using creatinine, age, sex and ethnicity through the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI).23.Patients were evaluated for liver fibrosis using the FIB-4 index, according to the following equation:2 and/or age > 40 years and two or more of the following conditions: serum glucose > 110 mg/dL, triglycerides > 150 mg/dL, HDL-cholesterol < 40 mg/dL in men and < 50 mg/dL in women, and blood pressure > 130/85 mmHg or pharmacologic treatment for hypertension24.MetS was defined as Body Mass Index (BMI) > 25 kg/mAll patients gave written informed consent, and the study design was approved by the Ethics Committee of the Hospital Universitari Germans Trias i Pujol . The methods complied with the ethical standards for medical research and the principles of good clinical practice in accordance with the World Medical Association’s Declaration of Helsinki.Descriptive statistics were expressed as median (interquartile range (IQR)) for quantitative variables and as absolute frequencies and percentages for qualitative variables.t test or Mann–Whitney U test in quantitative variables to analyze differences in patients with and without hyperuricemia. Correlations were determined using Pearson’s correlation coefficient.We used the Chi-square test for qualitative variables and Student’s Logistic regression models were applied to establish factors associated with hyperuricemia. Sociodemographic variables (age and sex), ESR, albumin and GGT levels, FIB-4, and MetS were analyzed after adjusting for eGFR; for these analysis the eGFR was considered a continuous variable and GGT levels were stratified as ≤ 50 U/L, 51–300 U/L, > 300 U/L, altered ESR was defined as > 20 mm and hypoalbuminaemia < 35 g/L.The covariates included in the multivariate analysis were those that were found to be statistically significant in the eGFR-adjusted univariate analysis.Sensitivity analyses of logistic regression models were performed to further analyze associations of hyperuricemia when using different SUA cut-offs. Lower cut-off values (6.0 mg/dL for men and 5.0 mg/dL for women), higher cut-off values (8.0 mg/dL for men and 6.5 mg/dL for women), and a single cut-off point (7.0 mg/dL for both sexes) were used.P values < 0.05 were considered statistically significant. Statistical analyses were performed using Stata software .2 , eGFR was 105 mL/min/1.73 m2 , 9.7% had MetS and 23% had advanced liver fibrosis (FIB-4 > 3.25). The prevalence of hyperuricemia was 12.5%.A total of 686 patients (77% men) were eligible, with a median age of 47 years . The age of onset of alcohol consumption was 16 years  and the amount of alcohol consumed was 160 g/day . BMI was 24.7 kg/mP = 0.041). Sex, educational level, employment and characteristics related to alcohol consumption and other substances were similar in those with and without hyperuricemia.Sociodemographic characteristics and data on the consumption of alcohol and other substances in patients with and without hyperuricemia are shown in Table P = 0.010), elevated GGT (P < 0.001), and lower eGFR (P = 0.001) than those without hyperuricemia. Specifically, the probability of presenting with hyperuricemia increased 1.5-fold for each decrease of 10 mL/min/1.73 m2 in the eGFR. A total of 24 (30.8%) patients among those with hyperuricemia and 121 (22%) among those without hyperuricemia had advanced liver fibrosis (FIB-4 > 3.25) (P = 0.087).The results of laboratory parameters upon admission are shown in Table 2 in the eGFR, SUA increased by 0.24 mg/dL .Figure P < 0.001). Specifically, relative to patients with GGT ≤ 50, those with GGT between 51 and 300 and those with GGT > 300 U/L were 4.31 (95% CI 1.62–11.46) and 10.3 (95% CI 3.50–29.90) times more likely to have hiperuricemia, respectively. The drastic differences between the odds ratios associated with FIB-4 obtained from univariate and multivariate logistic regression are due to strong confounding with GGT. Specifically, among those with FIB-4 ≤ 3.25, 31.9%, 53.2% and 14.9% had GGT ≤ 50, 51 < GGT ≤ 300 and GGT > 300 U/L, respectively; and in contrast, among those with FIB-4 > 3.25, the great majority had GGT > 300 with 2.1%, 30.6% and 67.4% having GGT ≤ 50, 51 < GGT ≤ 300 and GGT > 300 U/L, respectively. Likewise, among those with ESR ≤ 20 mm, 28.7%, 49.4% and 21.9% had GGT ≤ 50, 51 < GGT ≤ 300 and GGT > 300 U/L, respectively; and in contrast, among those with ESR > 20 mm, 17.2%, 43.3% and 39.5% had GGT ≤ 50, 51 < GGT ≤ 300 and GGT > 300 U/L, respectively.The eGFR-adjusted, logistic regression models are shown in Table The results of sensitivity analyses using different cut-off values for SUA were consistent with those presented here.25. More important, our data indicates a strong dose–response relationship between serum GGT and SUA levels after adjusting for potential confounders  and this finding may have implications in clinical practice and public health interventions. Studies have shown the role of serum GGT as a surrogate of oxidative stress28 and pointed out that both SUA and GGT are markers of cardio-metabolic risk32. In this sense, serum GGT is a marker of hepatic intracellular triglyceride accumulation that has been linked to obesity, insulin resistance, atherosclerosis34, and hyperuricemia regardless of alcohol consumption36.The role of excessive alcohol consumption in the risk of hyperuricemia/gout and metabolic complications is well known. However, few studies have analyzed the determinants of hyperuricemia in patients with eGFR-adjusted . The kidney is a key regulator of circulating uric acid levels by reabsorbing 90% of filtered urate and results from this large case-series indicates that one in eight patients with AUD had hyperuricemia. In addition, prevalence would reach 14% if we had included patients who were treated with uricosuric agents or diuretics upon admission; such similar prevalence of hyperuricemia has been reported in individuals with heavy alcohol consumption37. On the other hand, GGT plays a critical role in the metabolism of glutathione, a key antioxidant in humans, and there is a correlation between elevated GGT serum levels and oxidative stress leading to steatohepatitis38. Furthermore, uric acid itself promotes oxidative stress in adipocytes by increasing monocyte chemotactic protein-1 and decreasing adiponectin39. In addition, the pro-oxidant action of uric acid is also related to the accumulation of triglycerides in the liver (i.e. steatohepatitis)37.Serum GGT may be a contributing factor for hyperuricemia through oxidative stress and insulin resistance. Specifically, serum GGT is associated with hepatic insulin resistance, which in turn is correlated with hyperuricemia due to a reduction in urate excretion28. The other analyzed the general Japanese population and demonstrated a strong correlation between the two serum markers in both men and women40.Two studies in the general population have analyzed the connection between serum GGT and SUA. One study evaluated normotensive individuals free of liver, kidney, and metabolic diseases and found a positive correlation between serum GGT and urateTo the best of our knowledge, the present study is the first to report serum GGT as an independent contributing factor for hyperuricemia in AUD.15. With regard to the type of alcoholic beverage, several studies have shown that, in contrast to wine, the consumption of beer and spirits is related to higher SUA levels and to an increased risk of gout41. Notwithstanding, the absence of significant associations between hyperuricemia and the amount and type of alcohol consumed in our study population might be due to the large amount of alcohol ingested daily. In this respect, few studies have analyzed the association between SUA levels and the drinking pattern in the context of AUD. A population study in Taiwan (2017) involving 11,675 people with alcohol-related diseases, including alcohol dependence, suggested a positive relationship between long-term alcohol dependence and gout risk17.In this study, there were no significant differences in prevalence of hyperuricemia according to the amount and type of alcoholic beverage. A population study based on the US Third National Health and Nutritional Examination Survey (NHANES III) found that SUA levels increased as total alcohol intake increased6. Moreover, some cases of hyperuricemia could be hereditary due to inborn errors of purine and pyrimidine metabolism42; in addition, familial and twin studies estimating the heritability of SUA alterations suggest that genetic factors may explain up to 25–60% of the variability in SUA levels43. Finally, the cross-sectional design of this study did not allow the establishment of causal relationships.The present study has limitations that should be mentioned. First of all, variables related to the risk factors for hyperuricemia such as dietary habits were not available; in this sense, the link between fructose-rich beverages and purine-rich foods with hyperuricemia/gout is well knownIn conclusion, hyperuricemia was found to be relatively common in patients seeking treatment of AUD and closely linked to GGT which suggest an increased cardiometabolic risk in this population.


Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes an ongoing outbreak of respiratory illness called coronavirus disease 2019 (COVID‐19). The clinical course could be ranging from mild to severe illness especially the individuals with an immunocompromised condition such as solid organ transplant recipients.We described a family cluster of COVID‐19 patients who were admitted during 3rd April 2020 to 30th April 2020. COVID‐19 was confirmed by a presence of SARS‐CoV‐2 ribonucleic acid in the respiratory specimens detected by a qualitative, real‐time reverse transcription‐polymerase chain reaction. The study focused on the clinical course and management of our cases.A family cluster of four laboratory‐confirmed COVID‐19 patients, one of those carried an underlying kidney transplant (KT) receiving immunosuppressants. Clinical presentation and severity of our case series are variable depending on each individual immune status. By far, a KT recipient seems to develop more severity despite antiviral therapy, cessation of immunosuppressant, and aggressive intensive care support.Our case series plausibly affirmed a person‐to‐person transmission and potentially severe disease in the transplant population. Clinicians who are encountering with transplant recipients should be aware of possible transmission among family members. A family cluster of four laboratory‐confirmed COVID‐19 patients. Our case series plausibly affirmed a person‐to‐person transmission and potentially severe disease in the transplant population. Clinicians who are encountering with transplant recipients should be aware of possible transmission among family members. COVID‐19coronavirus disease 2019CRPC‐reactive proteinGFRglomerular filtration rateKTkidney transplantLDHlactate dehydrogenaseRT‐PCRreverse transcription‐polymerase chain reactionSARS‐CoV‐2severe acute respiratory syndrome coronavirusSOTsolid organ transplantWBCwhite blood cell1A novel betacoronavirus, the seventh member of coronaviruses, which is shown to infect humans and lately named as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes an ongoing outbreak of respiratory illness that began in December 2019 in China called coronavirus disease 2019 (COVID‐19). The first COVID‐19 case in Thailand, also the first recorded case outside of China, was reported in mid‐January 2020.22.13, lymphocyte (L) 18%, neutrophil (N) 78%, and C‐reactive protein (CRP) 62.7 mg/L. The chest X‐ray (CXR) revealed new small patchy opacities in the left lower lung field as shown in Figure A 58‐year‐old female who presented with fever and productive cough of 2 days duration on 2nd April 2020. She lived in Ngao, a city located in the northern region of Thailand. Her temperature was 37.9°C. The throat and lung exams did not reveal abnormal findings. She had chronic obstructive pulmonary disease (COPD) which was controlled by fluticasone/salmeterol and fenoterol/ipratropium bromide metered‐dose inhalers. She reported a history of contact with her daughter who had recently returned home from Bangkok, a city located in the central region of Thailand 2 weeks before this presentation. A timeline event of the cluster is shown in Figure 2.23 and L 31%. Her CXR was unremarkable. Therefore, she was diagnosed with mild COVID‐19, and treated with hydroxychloroquine 1200 mg/d, ritonavir‐boosted lopinavir 800 mg/d, and roxithromycin 300 mg/d. Finally, her clinical had improved and a repeated PCR for SARS‐CoV2 from nasopharyngeal and throat swab turned to negative on day 17 after treatment.A 42‐year‐old healthy female (the daughter of Case 1) who had worked in Bangkok as a businessman. She had contacted with a foreign visitor 3 weeks before the event. Few days before visiting her mother, she had fever with productive cough and sore throat however, her symptoms were spontaneously resolved without medical attention few days later. Then she was admitted because the history of closed contact with confirmed COVID‐19 and was found to be positive polymerase chain reaction (PCR) for SARS‐CoV2 from nasopharyngeal and throat swab. The physical examination was unremarkable. Blood test showed WBC 6260 cells/mm2.32/FiO2 ratio of 82  who lived nearby and reported visiting an index case every day. Although she reported being asymptomatic, her nasopharyngeal and throat swab for SARS‐CoV‐2 PCR was positive, and the CXR was unremarkable on admission. However, her respiratory symptoms had been progressing along with the CXR, which revealed the progression to patchy opacities in peripheral and basal both lungs. The diagnosis of acute respiratory distress syndrome (ARDS) was confirmed by PaO2 Figure  on day 92.42, respectively. He denied having recently augmented immunosuppression or previous opportunistic infections. He also had chronic hepatitis B on lamivudine 150 mg/d. The exam revealed body temperature of 38.0°C, blood pressure of 100/60 mm Hg, heart rate 60/minute and respiratory rate 16/minute. Otherwise was unremarkable. The initial blood test and CXR were normal. A diagnosis of COVID‐19 was suspected based on a history of contact with a confirmed COVID‐19 case (a primary case). He was empirically treated with oral oseltamivir and oral cefixime while waiting for nasopharyngeal and throat swab for SARS‐Co‐V2 PCR and influenza antigen, which both later revealed negative. However, his fever had persisted until day 6 of admission without localizing symptoms or signs hence for a reassessment for SARS‐CoV‐2 PCR from nasopharyngeal and throat swab, which reported as positive. The CXR also showed small patchy opacities at the left lower lung field, which was compatible with left lower lung COVID‐19 pneumonia. Hydroxychloroquine 800 mg/d, ritonavir‐boosted lopinavir 800 mg/d, azithromycin 250 mg/d, and favipiravir 1200 mg/d were initiated. Mycophenolate sodium was withdrawn, tacrolimus was decreased for low trough level and prednisolone was decreased to 15 mg/d. Intravenous ertapenem and levofloxacin were empirically started 2 days after clinical deteriorating. One week after treatment, he still had persistent fever, tachypnoea as well as new‐onset of diarrhea. The exam revealed respiratory rate of 28/minute with oxygen saturation 95% on oxygen 3 LPM. His labs included WBC 6200 cells/mm3, N 88%, creatinine 3.01 mg/dL, lactate dehydrogenase (LDH) 292 IU/mL, CRP 96.1 mg/L, ferritin 2790 ng/mL, and tacrolimus level 66.3 ng/mL. Temporal change in laboratory markers were shown in Figure 2, CRP 1.9 mf/L, LDH 142 IU/L, and serum ferritin 1459 ng/mL. Timeline after the onset of illness was shown in Figure Clostrioides difficile colitis requiring oral vancomycin and intravenous metronidazole.A 38‐year‐old man a son of Case 1) who underwent a living‐related KT in 2014 who complained of fever and myalgia for 3 days before this admission. He had a history of travel to Bangkok for a follow‐up visit 1 week before this event. His allograft has been maintained on tacrolimus 2 mg/d, mycophenolate sodium 720 mg/d, and prednisolone 5 mg/d. Baseline creatinine and estimated glomerular filtration rate (eGFR) was 0.9 mg/dL and 70.7 mL/minute/1.73 mase 1 who3A family cluster of laboratory‐confirmed COVID‐19 cases were reported from the setting where a lockdown policy was implemented. The manifestations were variable ranging from mild upper to severe lower respiratory tract disease leading to ARDS. These occur among family members of different ages and comorbidities. This case series confirmed a transmission among humans of SARS‐CoV‐2 is plausible, as documented in chronological time. Although acute hypoxemic respiratory failure from COVID‐19 in elderly and KT recipients in our cohort seemed to be prominent, early investigation in high‐risk populations, prompt initiation of potential therapy, and intensive supportive care are important to prevent adverse consequences and mortality.COVID‐19 has been emerging as respiratory tract illness and spreading worldwide. Although the majority could only experience mild respiratory symptoms, those with comorbidities, especially solid organ transplant (SOT) recipients, could potentially develop acute hypoxemic respiratory failure requiring ventilator support likely due to their immunosuppressed conditions.In addition, viral culture and serological diagnosis were not available due to limitations of serological validation and viral culture take times and require biosafety level‐3 for laboratory work.The transplantation society and the Infectious Diseases Society of America recommended confirming COVID‐19 diagnosis in transplant recipients with clinical presentation plus nucleic acid amplification test (NAAT) to detect the RNA of the virus.2 and eGFR less than 30 mL/minute/1.73 m2, receiving lymphocyte depletion therapy within 3 to 6 months, all immunosuppressants would need to discontinue and increase/start steroids at 15 to 25 mg/d. The exception is to attempt to keep dual therapy CNI‐steroids on those without risk factors. Antiviral agents such as favipiravir and remdesivir have been reported in the literature for potential effectiveness, although few immunocompromised patients were included.Apart from potential antiviral therapy, adjunctive therapies, and respiratory support, adjustment of immunosuppression is another cornerstone which needs to be focused among immunocompromised patients. The Department of Disease Control, Ministry of Public Health, Thailand, recommended hydroxychloroquine and boosted protease inhibitors, either lopinavir or darunavir, were given to those with mild (with comorbidities) and moderate symptoms without pneumonia. Favipiravir was suggested for those diagnosed with pneumonia.The European Renal Association‐European Dialysis and Transplant Association recommended all immunosuppressants to be continued in patients without symptoms. On the other hand, discontinuation of antimetabolites such as mycophenolic acid or azathioprine, and mammalian target of rapamycin (mTOR) inhibitors and maintained on a lower therapeutic range of calcineurin inhibitors (CNIs); 2 to 4 ng/mL for tacrolimus and 35 to 65 ng/mL for cyclosporin; and low‐dose steroid is recommended for symptomatic patients without pneumonia. Instead, all immunosuppressants would need to be discontinued among those with pneumonia.Drug interactions could possibly increase CNI and mTOR inhibitors while concurrent use with hydroxychloroquine. Therapeutic monitoring of their trough levels should be considered.Sepsis, ARDS, and multiorgan failure have been reported as complications from COVID‐19. The onset of pneumonia, ARDS, and superinfection in two cases were in the second weeks, which were comparable to the previous study.Finally, all patients had a clinical response to the treatment and negative PCR for COVID‐19. Repeated testing was done for all cases, and persistent positive RT‐PCR from lower respiratory tract specimens was found in KT recipient who had severe pneumonia. We assumed that sustained viral shedding beyond 14 days had been reported in several respiratory viral infections in immunocompromised patients such as influenza and lower respiratory tract specimens have high yield for late detection and monitoring of patients with severe COVID‐19 pneumonia.Our case series had a few limitations. First, the underestimation in the correlation between laboratory value and disease severity could be inevitable due to lacking all blood tests in all patients, especially those with mild disease because the results would not deem to influence the management. Second, the duration of viral shedding is limited due to limited NAAT testing in our setting. Third, we were not able to provide solid evidence of person‐to‐person transmission since we did not genetically investigate a whole‐genome sequencing of the virus. Last, a sole effect of favipiravir in our cases could not be concluded due to a confounding effect of multiple adjunctive therapies along with an adjustment of immunosuppressant. However, our case at least supports early multifacet management, including antiviral therapy, adjunctive therapy, adjustment of immunosuppressant and intensive care could prevent morbidity and mortality in these specific immunocompromised hosts.In summary, a family cluster of COVID‐19 had varied clinical presentation from mild infection to severe pneumonia complicated with ARDS. The main management is comprised of investigational antiviral therapy, adjustment of immunosuppressant, and respiratory support. Clinicians who are encountering transplant recipients should be aware of a possibility of transmission among the family members and the severe course of the disease.The authors declare that there are no conflict of interests.PS, JB, CP, and NC: conceptual designing of the study; PS and JB: collecting data and drafting the manuscript. All authors have reviewed and approved the manuscript submission.This study is approved by the medical ethical review of Lampang Hospital, Thailand. Subjects were informed of the purposes of the study and gave their signed informed consent.


Studies from both humans and animals experiments have offered abundant evidence supporting that mountain sickness is associated with changes in autonomic nervous function (ANF), which can be measured by heart rate variability (HRV).We aimed to assess changes of ANF in chronic mountain disease by measuring HRV in patients with high altitude pulmonary hypertension (HAPH).From November 2018 to March 2019, 120 patients in the cardiac care unit of the People's Hospital of Tibet Autonomous Region were selected as the observation group, and 50 patients without organic heart disease served as the control group. Pulmonary artery systolic pressure was evaluated by echocardiography in patients with HAPH, divided into three groups: mild (30‐49 mm Hg), moderate (50‐69 mm Hg) and severity (≥70 mm Hg) groups. A 24‐hour dynamic electrocardiogram (DCG) was obtained for each patient. HRV  indexes were measured and compared.Compared with the control group, time domain parameters including SDNN, SDANN, RMSSD, PNN50, and HRVTI were reduced, as well as frequency domain indexes such as TP, VLF, LF, and HF. LF/HF was highest in mild HAPH group and lowest in the moderate HAPH group, and the difference between the two groups was statistically significant.The HRV of patients with chronic HAPH in high altitude areas in Tibet is significantly reduced relative to healthy controls, and significantly negatively correlated with the severity of pulmonary artery hypertension. High‐altitude‐pulmonary hypertension (HAPH) is a specific disease affecting individuals at altitudes above 2500 m. The VI World Congress on Mountain Medicine & High Altitude Physiology unified it as high altitude pulmonary hypertension (HAPH).22.1The current survey was officially implemented after approval from the Medical Ethics Committee of the People's Hospital of Tibet Autonomous Region, China . All subjects or their families fully understood the purpose and methods of the study, and provided signed informed consent. There were no health interventions involving the subjects. All individual data were anonymous prior to analysis.2.22) levels were measured by hand‐held oxygen meter  in the second left finger. The control group consisted of 50 patients with no definite cardiopulmonary disease and no signs of pulmonary hypertension on echocardiography. The subjects were all Tibetans living at altitudes >3000 m. The baseline data of each group of subjects are shown in Table From November 2018 to May 2019, 120 patients with HAPH were admitted to the Cardiac Care Unit of the People's Hospital of Tibet Autonomous Region, including 64 males, aged 22‐84 (63.78 ± 1.56) years, and 56 females, aged 28‐84 (63.34 ± 1.33) years. Those taking calcium antagonists and β blockers affecting HRV were excluded. All participants provided written informed consent. All subjects were questioned about ethnicity, occupation, living altitude and detailed medical history after hospitalization, and underwent physical examination. Hemoglobin measurement, electrocardiography, 24‐hour dynamic electrocardiography (DCG), and echocardiography were performed within 48 hours of admission. Also, finger oxygen saturation  in June 2005, based on the European Heart Association and the European Respiratory Diseases Association and approved by the International Cardiopulmonary Transplant Association. The Guidelines for the Diagnosis and Treatment of High Pressures define the standard for pulmonary hypertension as the mean pulmonary artery pressure > 25 mm Hg2.4A Phillips EPIQ 7C (coPHILIPS) echocardiographic diagnostic system with probe frequencies ranging from 1 to 5 MHz was used to measure tricuspid regurgitation flow to calculate pulmonary systolic pressure (PASP). The grouping of the included subjects was determined by the measured values, and HAPH was classified into mild (30 to 49 mm Hg [1 mm Hg = 0.133 kPa]), moderate (50 to 69 mm Hg) and severe (≥70 mm Hg).Left ventricular ejection fraction (LVEF) was derived as follows: LVEF = (EDV‐ESV/EDV) × 100, where EDV and ESV are end diastolic volume and end systolic volume, respectively.2.5am and rest for 15 minutes before inspection. The DCG was recorded and replayed on a computer, excluding ventricular/supraventricular premature or other arrhythmias. The 24‐hour continuous DCG was recorded, and the ventricular/supraventricular premature contraction and interference were automatically eliminated by the software.Subject information was collected using a 12‐lead 24‐hour full information DCG system . Sampling requirements were: starting point at 9‐11 2.5.1Time‐domain indicators for 24‐hour long‐range analysis included SD of normal RR intervals (SDNN), SD of 5 minutes average normal RR intervals (SDANN), root mean square of successive difference in RR interval (RMSSD), percentage of RR intervals differing more than 50 ms from the preceding one (PNN50) and HRVTI, also called triangle index.am to 11:00 am, and frequency domain analysis was performed. The fast Fourier transform method (FFT) was employed. Frequency domain included total power (TP), very low frequency , low frequency , and high frequency .The frequency domain index was evaluated in a short time interval of 5 minutes. The subjects were arranged in a quiet time position from 9:00 2.6t test was performed to compare group pairs, and ANOVA was carried out to compare multiple groups. The LSD‐ or SNK‐q test was performed for data with homogeneous variance, and nonparametric tests for those with heterogeneous variance. Generalized linear model (GLM) analysis was used to adjust the confounders. The Kruskal‐Wallis test was performed for analysis. Multiple comparisons were performed by the Mann‐Whitney U test. For all tests, P values < .05 were considered statistically significant.Analyses were performed using SPSS (version 25.0). Parameters with normal distribution were expressed as mean ± SD (SD), and count data as percentage or number of cases. Independent samples 33.12 at the fingertip was decreased significantly in the HAPH group compared with control patients (P < .01). Hemoglobin were increased significantly in the HAPH group compared with control cases (P < .01). The HAPH course was 5.00 ± 0.65 years. It is worth noting that the average heart rate decreased progressively in with increasing HAPH severity (P < .05). At the same time, left ventricular ejection fraction decreased progressively with increasing pulmonary artery pressure (P < .05) , time domain indexes such as SDNN, SDANN, RMSSD, PNN50, and HRVTI progressively decreased from mild to severe groups of HAPH patients compared with control values, with statistically significant differences (P ≤ .001). Similarly, after adjustment for SaO2, frequency domain indexes such as TP, VLF, LF, and HF progressively decreased from mild to severe groups of HAPH patients compared with control values, and the differences were statistically significant (P ≤ .001). In patients with mild pulmonary hypertension, the LF/HF ratio was slightly elevated compared with controls (P = .03). Meanwhile, this ratio was lowest in patients with moderate pulmonary arterial pressure followed by the severe diseased patients; both groups showed significantly lower LF/HF ratios compared with control values (P < .001). These data are detailed in Table After adjustment for oxygen saturation SaO, time do3.2.1P < .01)  Table .4Individuals living at high altitudes for a long time could have a series of physiological or pathological changes due to low pressure, low oxygen concentration, dry and cold weather, elevated solar radiation and ultraviolet radiation, which affect pulmonary artery pressure. At present, the important role of autonomic nervous regulation in its development is not clear.HRV is currently the most widely used method for the evaluation of ANF. As a noninvasive quantitative indicator for judging cardiac autonomic nervous activity, HRV has been confirmed by many clinical trials.In the time domain of HRV, HRVTI represents the overall change of heart rate. SDNN and SDANN represent enhanced sympathetic activity. RMSSD and PNN50 represent weakened vagal activity, while RMSSD is more often used to evaluate vagal nerve function because of its good stability. The time domain analysis in this study was performed on a 24‐hour time course, so assessment of long‐term ANF in patients with HAPH is more accurate.In this study, with the increase of pulmonary artery pressure, all time domain indexes of patients with HAPH were significantly reduced. We observed a significant decrease in ANF in patients with chronic HAPH. HRV frequency domain analysis often uses short‐term studies, so it is more suitable for short‐term evaluation of ANF in patients with HAPH. The TP in the frequency domain represents the sum of high frequency, very low frequency, and ultralow frequency. LF was once used as a very important indicator of HRV to reflect the functional status of the sympathetic nerve. However, with further research, LF is no more considered an effective marker of autonomic nervous activity itself, because besides autonomic nervous system, it is also affected by baroreceptor activity.In addition, studies in China have shown that the incidence of sinus tachycardia in patients with type I pulmonary hypertension mainly including idiopathic pulmonary hypertension, congenital heart disease‐related pulmonary hypertension and connective tissue disease‐related pulmonary hypertension can reach 26%.4.12. Further validation studies are needed to verify these findings.We used noninvasive methods to assess pulmonary artery pressure and cardiac function in this study. These methods tend to underestimate the level of pulmonary arterial pressure, which is not as accurate as invasive measurement methods.The authors have declared that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.Figures S1‐10 The box charts of the average values of various HRV indexes.Click here for additional data file.


There are disputes about which reduction technique should be adopted in treatment of distal radius-ulna fractures in older children who failed to achieve manual reduction. This study compared clinical effects between prying reduction with mosquito forceps (PRMF) and limited open reduction (LOR) of treating irreducible distal radius-ulna fractures in older children.One hundred ten children with irreducible distal radius-ulna fractures were selected from January 2015 to December 2017 in Xi’an Hong Hui hospital. Retrospective analysis was performed. According to different reduction techniques, these children were divided into PRMF group (59 cases) and LOR group (51 cases). All children were treated with percutaneous Kirschner wire fixation and external fixation with plaster. Operation indexes, complications and wrist joint functions were compared between the two groups.P < 0.05). Incision length in PRMF group was less than that in LOR group (P < 0.05). Bleeding volume of PRMF group was less than that of LOR group (P < 0.05). Incidence of complications in PRMF group was lower than that in LOR group.Operation time of PRMF group was shorter than that of LOR group (Compared with limited open reduction, it has better clinical effects of prying reduction with mosquito forceps in treatment of irreducible distal radius-ulna fractures in older children. This technique has the advantages of simple operation, less trauma, less bleeding and fewer complications, which is worthy of clinical promotion. Distal radius-ulna fractures of children are one of the most common fracture types in children. According to literatures, distal radius-ulna fractures in children account for 31% of all fractures in children . The aveInclusion criteria: (1) Children aged 8–15 years; (2) Children with only distal radius-ulna fracture; (3) Children with only metaphyseal fracture; (4) According to AO/ASIF classification, children were classified as A1 and A2 fractures; (5) Children could be followed up completely. Exclusion criteria: (1) Children younger than 8 years or older than 15 years; (2) Children with multiple fractures; (3) Children achieved closed reduction successfully; (4) Children with open fractures; (5) Children need surgical exploration because of neurovascular injuries; (6) Children with incomplete clinical data.P > 0.05, Table General information: 110 children with irreducible distal radius-ulna fractures were selected from January 2015 to December 2017 in Xi’an Hong Hui hospital. All patients were treated with percutaneous Kirschner wire fixation and external fixation with plaster. There were 60 boys and 50 girls, aged between 8 and 15 years. According to AO/ASIF classification, all children were classified as A1 and A2 fractures. 59 cases were treated by PRMF technique while 51 cases by LOR technique. There was no significant difference in age, gender and fracture type between the two groups  score was used to compare the degree of wrist pain between the two groups. Palmar tilting angle and ulna deviation angle were compared of the two groups. Gartland werley  score waP < 0.05 was considered to be statistically significant.SPSS 23.0 software was used to process the data and measurement data were expressed as the mean ± standard deviation. The unpaired t test was used for comparisons between the two groups, including age, operation index and wrist function score. Count data were analyzed using the χ2 test, including gender and fracture classification. P < 0.05). The operation time of PRMF group was 25.4 ± 4.8 min, shorter than that of 36.8 ± 5.5 min in LOR group (P < 0.05). The bleeding volume of PRMF group was 5.8 ± 2.5 ml, less than LOR group of 20.6 ± 3.4 ml. The fluoroscopy times of PRMF group were 8.4 ± 1.5, which were more than LOR group of 4.7 ± 2.1 (P < 0.05). The above results are shown in Table The incision length of PRMF group was 0.5 ± 0.2 cm, which was smaller than LOR group of 4.2 ± 1.3 cm  returned to generally normal. The VAS score of wrist joint was 1.3 ± 0.6 in PRMF group and 1.2 ± 0.8 in LOR group (The incidence of common complications in PRMF group was lower than that in LOR group, including incision infection, skin irritation and nerve injury Table . No seriDistal part of ulna and radius is the junction of dense bone and cancellous bone. Cortical bone becomes thinner in this area. There is a lack of compact and regular bone plates and units. Epiphysis exists at the distal part of radius and ulna in children, where the growth rate exceeds the calcification of bone, resulting in relatively low bone mineral density. Therefore, distal part of ulna and radius is an anatomic weak area, which is prone to fracture. Distal radius-ulna fractures are common in children, and most of them are closed injuries , 2. The Children under 8 years old after fracture have a strong shaping ability . Most ofOperators may solve the problem of irreducible distal radius-ulna fractures by open reduction technique. According to displacement of the fracture, incision can be made on the palmar or dorsal side. However, open reduction is traumatic, bleeding, leaving surgical scars, and even a certain probability of damaging epiphysis, resulting in growth arrest and other serious complications. Some scholars used minimally invasive prying reduction technique of Kirschner wires in the treatment of irreducible distal radius fractures in children , 20. PavThe authors used mosquito forceps in older children with distal radius-ulna fractures, and achieved satisfactory reduction effects. Mosquito forceps are small and fine, with blunt tips, and are always available in the operating room. This design allows it to be inserted through a minimally invasive incision. Mosquito forceps can provide enough strength during prying reduction without increasing the risk of nerve and vascular injuries. Therefore, mosquito forceps can be a good tool for prying reduction. The authors’ retrospective study shows that, compared with limited open reduction, it has shorter incision length, less bleeding and shorter operation time of prying reduction with mosquito forceps. Due to the minimally invasive incision, only 0.5 cm, children feel mild pain postoperatively. A smaller incision means less damage to soft tissues and blood supplies, so that there is less bleeding during the operation process, and the incision is easier to heal. It can significantly shorten the hospitalization time of children after operation, which is also in line with the concept of accelerating rehabilitation. However, the fluoroscopy times were slightly increased during prying reduction. Clinicians should pay attention to radiation protection. Although both groups achieved good wrist functions, incidence of common postoperative complications was lower in PRMF group. Importantly, there are some pitfalls of PRMF technique that surgeon should avoid. Firstly, pay attention to gentle prying, do not break the fracture fragments. Secondly, in the process of prying, the two teeth of mosquito forceps should be closed to avoid clamping nerves and blood vessels. Thirdly, when the assistant assists through longitudinal traction, pay attention to avoid soft tissue traction injury. Fourthly, do not use the tip of mosquito forceps to probe the distal part of the fracture fragment excessively, so as to avoid damaging the epiphysis.There are still some limitations in this study. The number of children included in this study was small, and the follow-up time was short. This study was limited to the metaphysis of the distal radius and ulna, and did not include children with epiphyseal fractures. Sometimes, metaphyseal fracture and epiphyseal fracture can occur in one child at the same time. In addition, this study was a single center clinical study. In the future, the authors will further carry out multi-center clinical research. The above deficiencies will be corrected in further research.Satisfactory reduction can be achieved by both prying reduction with mosquito forceps and limited open reduction in older children with irreducible distal radius-ulna fractures. Compared with limited open reduction, it has better clinical effects of prying reduction with mosquito forceps. It has the advantages of simple operation, less trauma, less bleeding and fewer complications, which is worthy of clinical promotion.


PARP‐1 gene, is highly implicated in the susceptibility of cancer. However, the roles of PARP‐1 rs1136410 C>T on cancer risk vary from different studies. We comprehensively screened all qualified publications from several databases, including PubMed, EMBASE, MEDLINE, CNKI and Wanfang. The searching was updated to April 2020. Our meta‐analysis included 60 articles with 65 studies, comprised of a total of 23 996 cases with cancer and 33 015 controls. Overall, pooled data showed that the PARP‐1 rs1136410 C>T polymorphism was significantly but a border‐line associated with an increased risk of overall cancer . Subgroup analysis indicated that rs1136410 C allele contributed to high risk among gastric, thyroid, and cervical cancer, but lower risk among brain cancer. Furthermore, increased cancer risk was detected in the subgroups of Asian, controls from population‐based design studies, and HWE ≤ 0.05 studies. Sensitivity analysis and Egger's test showed that results of the meta‐analysis were fairly stable. The current study indicated that PARP1 rs1136410 C>T polymorphism may have an impact on certain types of cancer susceptibility.Poly(ADP‐ribose) polymerase‐1 (PARP‐1) is a nuclear chromatin‐associated enzyme involved in the DNA damage response. SNP rs1136410 C>T, the most studied polymorphism in  Numerous SNPs have been identified in PARP‐1 gene. Among them, rs1136410 T>C  is a non‐synonymous polymorphism that could change valine to alanine. PARP‐1 rs1136410 T>C genetic polymorphism was previously investigated in various types of cancer. However, the results of epidemiological studies are inconsistent and contradictory. The present work aims to fill this gap in the literature by presenting the latest updated meta‐analysis of the available evidence in elucidating the relationship of PARP‐1 rs1136410 T>C and the risk of cancer.Poly(ADP‐ribose) polymerases (PARP), also known as ADP‐ribosyl‐transferase diphtheria toxin‐like (ARTDs), are evolutionary‐conserved family of proteins involved in diverse biological.22.1PubMed, EMBASE, MEDLINE, Wanfang, and CNKI were searched for English/Chinese‐language articles published from January 1990, through April 2020. The following syntaxes were used: (a) PARP‐1 or poly (ADP‐ribose) polymerase 1 or PARP1 or ADPRT or ADPRT1 or rs1136410 C>T; (b) SNPs or polymorphisms or polymorphism or variants; (c) cancer or cancers or carcinoma or tumour or neoplasm. To obtain other appropriate publications, we also manually examined the references of the selected articles. Eligible criteria were as follows: (a) case‐control study; (b) assessing rs1136410 C>T and cancer risk; and (c) enough information in allele frequency. Editorials, reviews, meta‐analysis, case‐only studies, duplicate studies were ruled out.2.2For each included study, a reviewer (H. Li) abstracted relevant study characteristics:  and classified the data into a structured form. Another reviewer (Y. Zha) checked all data for completeness and accuracy. Disagree parts (the conflicted information extraction by the two authors) were resolved through discussion until consensus was made.2.3P > .05 indicates not violating HWE. The association between PARP‐1 rs1136410 C>T and cancer risk were assessed by calculating ORs with the corresponding 95% CIs. Significant heterogeneity exists if I2 > 50%. If so, the random‐effect model was adopted, otherwise, the fixed‐effect model was used. Subgroup analyses by ethnicity, cancer type, source of control, and HWE in controls were performed to detect the source of heterogeneity. We also assessed the quality of each included study, the detailed method was described elsewhere.P value < .05 implies a significant finding.We used a chi‐square test to determine if genotype frequencies in controls of each study conformed to Hardy‐Weinberg equilibrium (HWE). 33.1Initial retrieval from PubMed, EMBASE, and MEDLINE databases got a total of 298 potentially relevant published records. We also obtained 12 articles from CNKI and Wanfang database. After titles and abstracts screening, 248 not relevant records were excluded. 4 articles were excluded due to being covered by others. A total of 58 case‐control design articles with reporting frequency of genotypes were included. Additionally, 2 eligible articles were also identified from references cited in the obtained articles. Ultimately, 65 studies from 60 publications were included Table . A total3.2The main results of the meta‐analysis were shown in Table 3.3Q test (P < .001) implied an existence of significant heterogeneity under all the genetic models. Therefore, a random‐effect model was applied to produce ORs and 95% CIs. In addition, the sequential sensitivity analysis was conducted to give an evaluation of the impact of a single study on the pooled ORs. The data of meta‐analysis is of great reliability, as no statistical fluctuation of the pooled ORs incurred after omitting in each study ; Writing‐original draft . Yong‐Jiu Zha: Data curation ; Writing‐original draft . Jie Liu: Methodology ; Software (supporting); Validation . Fang Du: Investigation ; Software ; Supervision . Xiao‐Quan Li: Supervision ; Visualization ; Writing‐review & editing . Xu Zhao: Funding acquisition ; Resources ; Supervision ; Visualization ; Writing‐review & editing .App S1Click here for additional data file.


Ventriculo‐pleural (VPL) shunt insertion is performed in hydrocephalic patients when alternative sites of cerebrospinal fluid (CSF) diversion are contraindicated. These include patients with peritoneal complications from ventriculo‐peritoneal shunts. Despite its utility, VPL shunts are uncommon. Hydrothoraces should be considered as a potential cause of dyspnoea in the setting of a VPL shunt. We present a case of worsening respiratory failure in the setting of a massive CSF hydrothorax in a hydrocephalic patient with a VPL shunt to highlight this potential complication of pleural CSF diversion, and present a potential management strategy in patients with premorbid underlying lung pathology. In this case, the hydrothorax was drained and the shunt was converted to ventriculo‐atrial (VA) shunt. We present a case of an adult hydrocephalic patient with a ventriculo‐pleural shunt in situ presenting with worsening respiratory failure in the setting of a massive cerebrospinal fluid hydrothorax. Ventriculo‐peritoneal (VP) shunt insertion is commonly performed in the management of communicating hydrocephalus, mitigating the risk of rising intracranial pressure and cerebral herniation through diversion of cerebrospinal fluid (CSF) to the peritoneal cavity . VP shunA 44‐year‐old female was referred after a telehealth conference with a six‐month history of worsening dyspnoea, orthopnoea, and increasing non‐invasive ventilation (NIV) dependence (from 10 h per day to 23 h per day). She became profoundly dyspnoeic when NIV was withdrawn for meals and showers. There were no preceding infective symptoms. The patient denied headaches, nausea, vomiting, and had no change in her conscious state.1) of 0.43 L (17% predicted), forced vital capacity (FVC) of 0.44 L (15% predicted), and forced expiratory ratio (FER) of 84%.Her past medical history included cerebral palsy, type 2 diabetes mellitus, and previous pulmonary embolism. She was treated with NIV for chronic ventilatory failure due to central and obstructive sleep apnoea, kyphoscoliosis, and chronic right hemi‐diaphragm elevation secondary to hemidiaphragm paralysis. Spirometry four years prior to presentation in 2016 revealed severe restriction, with a forced expiratory volume in 1 sec  shunt inserted at age two years for hydrocephalus of unclear aetiology. Due to growth‐related catheter migration, a revision was made to a VP shunt 12 years later. Following abdominal sepsis secondary to appendiceal perforation, the VP shunt was revised to a VPL shunt at age 26 years.Previous chest X‐rays (CXR) at age 36 years had identified the presence of a moderate right‐sided pleural effusion. However, given the absence of respiratory symptoms and concern regarding the risk of shunt infection, the fluid was not sampled at that time.2O and expiratory positive airway pressure (EPAP): 7 cm H2O). These settings were unchanged prior to and during the course of her illness. She was haemodynamically stable with no features of a tension hydrothorax. Breath sounds were absent over the right lung field. The patient was clinically euvolaemic.On examination, oxygen saturations were maintained at 100% on room air on NIV (inspiratory positive airway pressure (IPAP): 22 cm H9/L (4.0–12.0 × 109/L), C‐reactive protein (CRP) of 15.2 mg/L (<5.0 mg/L), brain natriuretic peptide (BNP) of 69 ng/L (<125 ng/L), albumin of 37 g/L (35–52 g/L), and creatinine of 28 μmol/L (45–90 μmol/L). A transthoracic echocardiogram demonstrated normal systolic function with mildly elevated pulmonary artery pressures of 34 mmHg (<25 mmHg). These results suggested that an infective, cardiac, hepatic, or renal cause for the pleural effusion were unlikely differentials.A CXR demonstrated complete opacification of the right hemi‐thorax Fig. . A subseThe pleural fluid was drained via a 14‐Fr pigtail catheter, with a total output of 2.5 L of light yellow, serous fluid. Biochemical results displayed a total protein of <30 g/L and lactate dehydrogenase (LDH) of 90 U/L, consistent with a transudative effusion by Light et al.'s criteria [A CT‐chest performed following removal of the drain showed no pulmonary nodules or masses.2) was within normal limits at 36 (35–45 mmHg).Following the drainage, the patient's dyspnoea improved and she no longer required daytime NIV. Her respiratory rate was 18 breaths per minute, and her oxygen saturations were 100% on room air. Subsequent arterial blood gas analysis showed a pH of 7.40 (7.35–7.45) and partial pressure of carbon dioxide , sub‐arachnoid haemorrhage, and malignancy . Hung etPleural effusions following VPL shunting is common. Thus, it should be considered as an important differential diagnosis in patients with VPL shunts who present with shortness of breath. The indication for thoracocentesis and shunt relocation are complex decisions that should involve a multidisciplinary team approach between the treating team and neurosurgical unit with operator experience. In adult patients with hydrocephalus and concomitant lung disease requiring VP shunt revision, VA shunt placement may be considered preferential to VPL shunt.Appropriate written informed consent was obtained for publication of this case report and accompanying images.


To investigate brain perfusion patterns in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric systemic lupus erythematosus  and to identify biomarkers for the diagnosis of NPSLE using noninvasive three‐dimensional (3D) arterial spin labeling (ASL). Thirty‐one NPSLE and 24 non‐NPSLE patients and 32 age‐ and sex‐matched normal controls (NCs) were recruited. Three‐dimensional ASL‐MRI was applied to quantify cerebral perfusion. Whole brain, gray (GM) and white matter (WM), and voxel‐based analysis (VBA) were performed to explore perfusion characteristics. Correlation analysis was performed to find the relationship between the perfusion measures, lesion volumes, and clinical variables. Receiver operating characteristic (ROC) analysis and support vector machine (SVM) classification were applied to differentiate NPSLE patients from non‐NPSLE patients and healthy controls. Compared to NCs, NPSLE patients showed increased cerebral blood flow (CBF) within WM but decreased CBF within GM, while non‐NPSLE patients showed increased CBF within both GM and WM. Compared to non‐NPSLE patients, NPSLE patients showed significantly reduced CBF in the frontal gyrus, cerebellum, and corpus callosum. CBF within several brain regions such as cingulate and corpus callosum showed significant correlations with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index scores. ROC analysis showed moderate performance in distinguishing NPSLE from non‐NPSLE patients with AUCs > 0.7, while SVM analysis demonstrated that CBF within the corpus callosum achieved an accuracy of 83.6% in distinguishing NPSLE from non‐NPSLE patients. Different brain perfusion patterns were observed between NPSLE and non‐NPSLE patients. CBF measured by noninvasive 3D ASL could be a useful biomarker for the diagnosis and disease monitoring of NPSLE and non‐NPSLE patients. It has a wide range of clinical neurological and psychiatric manifestations  that decrease quality of life  and single‐photon emission computed tomography (SPECT) studies, which could provide early biomarkers for SLE  but low specificity (<67%) in diagnosing NPSLE  imaging, which is a contrast agent‐free perfusion imaging technique, has been validated as being useful for the evaluation of brain perfusion related to various neurological and psychiatric diseases, including Alzheimer's disease, Parkinson's disease, brain tumor, stroke, seizures, and schizophrenia  and 35 non‐NPSLE patients (aged 29.24 ± 9.84 years) from the Department of Rheumatology, Peking Union Medical College Hospital and 36 female age‐matched NCs (aged 32.50 ± 10.57), were enrolled in this study. SLE and the manifestations of NPSLE were diagnosed and defined according to the American College of Rheumatology (ACR) classification and Hanly B criteria for SLE . The 3D T1w images were obtained by a 3D T1 MPRAGE (Magnetic Prepared RApid Gradient Echo) sequence with the following parameters: TR/TE = 1,600 ms/2.13 ms; inversion time = 1,000 ms; Flip angle = 9°; field of view = 240 mm × 240 mm × 160 mm; acquisition voxel = 1 mm × 1 mm × 1 mm; sense factor 1 for slice encoding direction and 2 for phase encoding direction; and acquisition time = 6 min. The 3D pseudocontinuous ASL images were obtained by a 3D TSE sequence with the following parameters: TR/TE = 4,844 ms/10.5 ms; flip angle = 111°; field of view = 240 mm × 240 mm; acquisition voxel = 1.875 mm × 1.875 mm × 4 mm; slice number = 36; number of signal average = 1; labeling duration = 1,500 ms; postlabeling delay time = 2,000 ms; acquisition time = 3 min 34 s. Additionally, axial 3 mm FLAIR images were acquired to assess WM lesions.2.3ASL image preprocessing was carried out using the ASAP (Automatic Software for ASL Processing) toolbox  level comparisons, the mean CBF within GM, WM, and WB (GM + WM) were calculated. A CBF ratio of GM/WM was obtained by dividing the mean CBF within GM by the mean CBF within WM. For voxel level comparisons, voxel‐based analysis (VBA) was performed to find the altered CBF of the local brain regions.2.4U test for nonparametric analysis). For categorical data, Fisher's exact test was carried out. For ASL images, voxel‐based statistical analysis was performed using ANOVA with age as a covariate, followed by a pairwise two‐sample t‐test with 5,000 permutations to define the t‐value threshold. An uncorrected p < .01 and cluster size >30 voxels were considered to be a significant difference. The Pearson correlation coefficient or the Spearman rank correlation, with age as a covariate, was applied to find the relationship between the values extracted from brain regions, WM lesions and the clinical evaluations . For the above analysis, a p < .05 was considered a significant difference. Receiver operating characteristic (ROC) analysis was carried out to differentiate NPSLE from non‐NPSLE by the CBF of the WB level or voxel level, which showed significant differences between NPSLE and non‐NPSLE. The cut‐off value was determined according to the maximum Youden index.Statistical analyses were carried out using IBM SPSS statistics Version 25 and the DPABI toolbox  with a Gaussian kernel function based on LIBSVM (Library for Support Vector Machines) and MATLAB scripts (MATLAB 2014b) was adopted for the classification of NPSLE and non‐NPSLE patients and NCs . As the WM lesion distribution map  showed weak correlations with clinical information including SLEDAI and SLICC scores and showed no significant correlation with disease duration, total cumulative duration of steroid use, or WM lesion volume when age was used as a covariate. The details of this analysis are shown in Table We found no significant association between CBF measures and other clinical information  or laboratory parameters  related to the manifestation of SLE, vascular risk factors and immunological indicators.3.5Differentiating non‐NPSLE and NPSLE is a challenge in clinical practice. In this work, the ratio of GM/WM was used to distinguish non‐NPSLE from NPSLE. The ROC analysis results are shown in Table We also investigated the ability of regional brain measurements to differentiate NPSLE from non‐NPSLE. ROC analysis showed that all the statistically significant brain regions, such as the right cerebellum posterior lobe, bilateral superior and middle frontal gyrus and corpus callosum, showed a moderate performance (AUC > 0.7) for differentiating non‐NPSLE from NPSLE. The details of this analysis are shown in Table 3.6The classification results are listed in Table 4In the present study, we identified different cerebral perfusion patterns between non‐NPSLE and NPSLE patients. In non‐NPSLE patients, within GM, CBF was decreased in the right inferior frontal gyrus but increased in the bilateral cerebellum, right temporal gyrus and left lingual gyrus compared to NCs. Within WM, distributed increased CBF was observed compared to NCs. In NPSLE patients, CBF in the bilateral frontal gyrus, temporal gyrus and middle cingulum gyrus decreased compared to that in NCs, while CBF was increased in most of the WM regions except the corpus callosum. The main differences between NPSLE and non‐NPSLE were in the frontal lobe and cerebellum (GM) and in the corpus callosum (WM). Perfusion patterns can accurately classify NPSLE and non‐NPSLE patients with CBF, which could be a potential imaging biomarker for the differentiation of non‐NPSLE and NPSLE.Our data demonstrated an increase in GM perfusion in non‐NPSLE patients and a decrease in NPSLE patients, implying the dynamic progression of perfusion alterations. Cohen et al.  proposedHistopathological studies revealed that nonspecific focal vasculopathy appeared in non‐NPSLE, while diffuse vasculopathy and microthrombi were commonly found in NPSLE, which is the possible pathological basis for different patterns of perfusion abnormalities , right cingulate/precentral lobe (WM), and SLEDAI measures in non‐NPSLE patients, implying that the hypoperfusion of these brain areas could reflect high disease activity that requires aggressive treatment.The differentiation of NPSLE patients from non‐NPSLE patients and NCs is essential in clinical practice. The previously proposed imaging measures have high sensitivity (80–100%) but relatively low specificity (<67%) with PET, SPECT or DSC‐MRI  study with a relatively small sample size from a single center. A longitudinal study using multimodality techniques, such as structural and functional MRI and PET/SPECT, in a large sample size from multi‐site centers is warranted to validate the current findings. Second, cognitive and neuropsychiatric assessments were not comprehensively performed, hindering the investigation between perfusion and neuropsychiatric scores. Third, the lesion effect on CBF alterations in SLE is not fully demonstrated in the current study. Further study with longitudinal data and comprehensive analysis is required to investigate the association between lesions and CBF in SLE patients (Gasparovic et al., 5Different brain perfusion patterns were observed in NPSLE and non‐NPSLE patients using the noninvasive ASL technique and were correlated with clinical scores, implying that perfusion characteristics could be a useful biomarker reflecting pathophysiological alterations and identifying NPSLE.None declared.The project was designed, conceived and planned by Y.L., X.Z., and H.L. The data acquisition was performed by L.S. The data were processed and analyzed by Z.Z. The article was written and edited by Z.Z. and L.S. The article was revised by Y.D., J.H., X.Q., and S.H. All authors approved the final version of the manuscript.Obtained.Table S1 Details of the clinical information and laboratory parameters of the SLE subjects included in this work.Click here for additional data file.Figure S1 The white matter lesion probability map. The map was presented by the ratio of the number of SLE patients with lesions and the total number of SLE patients as shown in the color bar.Click here for additional data file.Figure S2 The ROC analysis of GM/WM ratio for the differentiation of NPSLE and non‐NPSLE. The red point indicated the cut‐off value.Click here for additional data file.


Individuals living in poverty often visit their primary care physician for health problems resulting from unmet legal needs. Providing legal services for those in need may therefore improve health outcomes. Poverty is a social determinant of health. Impoverished areas tend to have poor health outcomes, with higher rates of mental illness, chronic disease, and comorbidity. This study reports on a medical-legal collaboration delivered in a healthcare setting between health professionals and lawyers as a novel way to approach the inaccessibility of legal services for those in need., patients aged 18 or older were either approached or referred to complete a screening tool to identify areas of concern. Patients deemed to have a legal problem were offered an appointment at the Legal Health Clinic, where lawyers provided legal advice, referrals, and services for patients of the physicians. Fisher’s exact test was used to compare populations. Binary logistic regression was used to determine the factors predicting booking an appointment with the clinic.In this observational studyn = 648) of the 770 patients screened had unmet legal needs and could benefit from the intervention, with an average of 3.44 (SD = 3.42) legal needs per patient screened. Patients with legal needs had significantly higher odds of attending the Legal Health Clinic if they were an ethnicity that was not white , did not have Canadian citizenship , had housing insecurity , and had difficulty performing their usual activities . As a result of the clinic consultations, 58.0% (n = 40) were referred to either Legal Aid Ontario or Hamilton Community Legal Clinic, 21.74% (n = 15) were referred to a private lawyer; one case was taken on by the clinic lawyer.Eighty-four percent (The Legal Health Clinic was found to fulfill unmet legal needs which were abundant in this urban family practice. This has important implications for the future health of patients and clinical practice. Utilizing a Legal Health Clinic could translate into improved health outcomes for patients by helping overcome barriers in accessing legal services and addressing social causes of adverse health outcomes. Patients living in poverty often consult with their family physicians for assistance with health problems that are the result of unidentified and unmet legal needs . Data frIn 2016, 13% or 4.5 million Canadians were living in poverty  based onMedical-legal collaborations delivered in a healthcare setting between health professionals and lawyers can present a novel way to approach these types of problems, by addressing the legal needs that influence poverty , 16. TheWith 15% of residents below the LIM definition of poverty  and a hiWhat are the types of legal needs identified when screening in a primary care setting?What are the characteristics of the population with legal needs in primary care and are they significantly different from those without legal needs in the same setting?What characteristics are associated with individuals choosing to access the legal health clinic?This paper reports the development of a novel legal assessment clinic embedded within primary care and explores the following research questions:A Legal Health Clinic (LHC) in an urban primary care setting was developed and implemented. A cross-sectional observational design was used to evaluate the amount of legal need in primary care, the characteristics of those with legal needs and of LHC attendees. Ethical clearance was granted by the Hamilton Integrated Research Ethics Board.Patients aged 18 years or over were either approached in the family practice waiting room by a research assistant to complete a screening tool  [The study was set in a primary care medical clinic within a family health team (FHT) with approximately 13,000 patients, in Hamilton, Ontario.This study involved providing legal aid services, in the form of a weekly clinic for patients of the FHT’s physicians. The legal clinic was created through a three-way partnership: between the FHT, Hamilton Community Legal Clinic (HCLC) and Legal Aid Ontario (LAO). A lawyer from each legal partner was onsite in the FHT clinical space, every week, on an alternating basis. The lawyers provided legal advice on multiple domains of law. The HCLC lawyer had expertise with housing, employment, social assistance, and human rights issues while the LAO lawyer had expertise on criminal, family, refugee, and estate law. As a result, the McMaster Family Practice LHC became available as a free service to patients of the FHT during this study, with the intention to continue afterwards if it was deemed feasible.The Legal Health Check-Up survey  was usedIn conjunction with the Legal Health Check-Up survey, participants also completed a study survey asking their demographics , quality of life (EQ-5D-3L),  self-repThe LIM 50 is a common poverty threshold used internationally . The indAt the LHC appointment, participants were scheduled for a 30-min consultation with one of the two lawyers. There were several possible outcomes. Some participants would be provided with resources or educated about an area of law and that would be sufficient to either solve or help with their legal problem. Participants who needed more assistance would be referred to one of four options: 1) LAO, if their income was low enough to qualify for Legal Aid services ; 2) HCLCInformation on the Legal Health Check-up survey was uploaded to the participants’ medical charts automatically. If the participant provided written consent, information from their legal appointment was added to their electronic medical record, visible to their family physician. The study research assistant scanned the paper documentation and uploaded it to the participant’s electronic medical record. Lawyers were not given access to the participant’s medical record. If the participant agreed, the legal team communicated with the medical team to arrange necessary items such as physical examinations for the Workers Insurance Safety Board. The lawyers would also recommend that the participant visit other services within the FHT, such as the system navigator, where appropriate.Measures were assessed using descriptive analysis, including the number of screening surveys completed, number of LHC appointments and subsequent referrals, and types of legal issues identified. Rates and frequencies of demographic characteristics of those who completed the LHC screening survey, of those with unmet legal needs, of those who made an appointment for the LHC and of those who kept their appointment with the LHC were calculated. Where appropriate chi-squared or Fisher’s Exact tests were used to compare populations. Binary logistic regression was completed to determine the factors predicting booking an appointment with the LHC. All statistical tests were performed on SPSS versions 20 and 24.n = 758) and the remaining participants were patients referred directly to the LHC by another source . Of the 12 participants referred directly to the LHC, five were referred by their physician within the FHT, five by the FHT system navigator, and two by other patients.In the first 6 months of the program, between April 25, 2016 and October 24, 2016, 770 patients from the FHT consented to participate in the study and completed the Legal Health Check-Up survey. Almost all participants were recruited while waiting as patients in the clinic waiting room , of those who had at least one legal need , and of those who had no legal need  are summarized in Table The demographic characteristics of all participants who completed the study survey , except for gender (p = 0.188)  had income insecurity, 21.9% (n = 169) could not afford their medication, 12.2% (n = 89) could not afford food, and 11% (n = 80) had housing insecurity (see Table n = 149) had a household income below LIM-50, indicating that their household income fell into the poverty bracket. Self-reported Health Status for the full survey sample was Very Good or Excellent in 40.4% (n = 298) of respondents. The EQ-5D-3L tool measuring five domains of quality of life showed that 28.5% (n = 208) had mobility issues, 8.0% (n = 58) had difficulties with self-care, 34.7% (n = 253) had issues performing usual activities, 60.6% (n = 443) had issues with pain or discomfort, and 51.9% (n = 376) had some or severe anxiety or depression.The 770 participants who completed the study survey predominantly screened negative for each poverty indicator; 38.1% n = 93 had inp < 0.05), except for pain and discomfort (p = 0.214) (see Table n = 140) of those with a legal need had a household income below LIM-50, compared to 15.8% (n = 9) of those without a legal need. In those with a legal need, 9.7% (n = 60) had a self-reported health status of ‘poor’ compared to 0% of those without a legal need. Also, the most frequent response for self-reported health status was ‘fair or good’ among those with a legal need , while the most frequent response was ‘very good or excellent’ among those without a legal need . Finally, the EQ-5D-3L tool measuring five domains of quality of life showed those with a legal need more frequently had difficulty with mobility (30.6% versus 17.2%), self-care (9.1% versus 1.7%), performing usual activities (38.3% versus 15.5%), and anxiety/depression (55.6% versus 31.6%).When comparing those who had a legal need to those who did not, using Fisher’s Exact tests, all poverty, health status, and quality of life variables showed a significant difference (rt p = 0.14 (see Tn = 537), income , employment , housing , and health . Details on the subcategories for each of these five types of legal needs and their frequencies can be seen in Table n = 486) of respondents did not have a will, 45.2% (n = 293) had trouble making ends meet, 31.2% (n = 202) did not have someone to make health decisions if they become unable, 30.1% (n = 195) had been hurt at work, 24.8% (n = 161) needed help getting or keeping their benefits, and 24.1% (n = 156) were in a relationship where someone was trying to control them.Using the Legal Health Check-Up tool, 2648 legal needs were identified through screening and 648 (84.2%) participants had at least one legal need. There was an average of 3.44 (SD = 3.42) legal needs per participant screened and an average of 4.09 (SD = 3.35) legal needs per participant who had at least one legal issue; see Fig. The Legal Health Check-Up tool also identified that all 770 participants screened (100%) had at least one issue related to social determinants of health that could be referred to the system navigator (e.g. assistance accessing subsidized daycare). A total of 5371 issues were identified through screening and there was a mean of 6.98 issues (SD = 4.29) per participant screened.Of the 648 participants identified through screening to have a legal need, 94 14.5%) booked an appointment with the LHC; of the 94 who booked, 69 (73.4%) attended the LHC once and five (5.3%) attended twice. In Table % booked n = 41), did not complete post-secondary education , were not employed full-time , were receiving benefits , did not own their residence , were not married or common-law , were Canadian citizens , and were white . The 18–24 year old age category had the lowest representation  and both the 35–44 and 45–54 year old categories had the highest representation (25.0% and n = 17 for both age categories). Please see Table In the 69 participants who did attend the LHC, the majority were female 59.4%, %, n = 41n = 54) reporting income insecurity, 58.0% (n = 40) unable to afford their medication, 56.9% (n = 37) having food insecurity, and 39.1% (n = 25) having housing insecurity. In the subset of 27 respondents who provided household size, 88.9% (n = 24) had a household income below the LIM-50 threshold. Self-Reported Health Status in LHC attendees was quite low, with only 7.7% (n = 5) reporting ‘excellent’ or ‘very good’ health, 67.7% (n = 44) reporting ‘good’ or ‘fair’ health, and 24.6% (n = 16) reporting ‘poor’ health. Quality of life was similarly low among attendees with 85.9% (n = 64) reporting pain or discomfort, 78.1% (n = 50) difficulty performing their usual activities, 74.6% (n = 47) anxiety or depression, 65.6% (n = 42) mobility problems, and 25.0% (n = 16) problems with self-care (e.g. dressing unassisted).The poverty indicators were common among LHC attendees (see Table n = 66) had a legal need related to family/community, 89.9% (n = 62) income, 75.4% (n = 52) employment, 69.6% (n = 48) housing, and 59.4% (n = 41) health. The frequencies for each subcategory of legal need can be seen in Table n = 59) of attendees did not have a will, 78.3% (n = 54) had trouble making ends meet, 56.5% (n = 39) needed help getting or keeping their benefits, 53.6% (n = 37) did not have someone to make health decisions if they become unable, 43.5% (n = 30) had been hurt at work, 43.5% (n = 30) were in a relationship where someone was trying to control them, 36.2% (n = 25) had problems with their home (e.g. heat not working), and 36.2% (n = 25) were having trouble finding work due to discrimination.Looking at the types of legal needs in attendees  were referred to either LAO or HCLC, depending on their income level and area of law needed, 21.74% (n = 15) were referred to a private lawyer, and one case was taken on by the LHC lawyer. This does not include cases that were taken on by lawyers at LAO or HCLC post-referral. Also, 47.8% (n = 33) of participants were provided education and 29.0% (n = 20) of participants were provided resources.As a result of the LHC consultations, 58.0% , the rate of observed legal needs is similar to those found in studies from the USA and Canada suggesting that each low-income household has three or more legal needs per year , 30. TheWe also found that those with a legal need were more vulnerable compared to those without, with higher rates of housing insecurity, food insecurity, and income insecurity. It has been suggested in Canada that the vulnerability of this population makes them less likely to seek legal assistance,  however One of the limitations of this paper is that the Legal Clinic was only provided in an academic FHT, located in the inner city, urban setting of Hamilton, Ontario. It is possible that in different settings the results would have been different. It is likely though, that the results of this paper are generalizable to other inner cities settings with similar populations.The McMaster Family Practice Legal Clinic has important implications for the future health of patients, as well as for clinical practice. The Legal Clinic is taking an “upstream” approach to addressing the social determinants of health by ensuring patients receive timely access to the legal services for which they otherwise may have not received help. By helping patients overcome the barrier in accessing legal services and therefore addressing underlying social causes of adverse health outcomes, and though this paper does not measure health outcomes, it is likely that accessing the Legal Clinic will translate into improved health outcomes for these patients , 13, 14.


Cardiac injury is common in COVID‐19 patients and is associated with increased mortality. However, it remains unclear if reduced cardiac function is associated with cardiac injury, and additionally if mortality risk is increased among those with reduced cardiac function in COVID‐19 patients.The aim of this study was to assess cardiac function among COVID‐19 patients with and without biomarkers of cardiac injury and to determine the mortality risk associated with reduced cardiac function.This retrospective cohort study analyzed 143 consecutive COVID‐19 patients who had an echocardiogram during hospitalization between March 1, 2020 and May 5, 2020. The mean age was 67 ± 16 years. Cardiac troponin‐I was available in 131 patients and an increased value (>0.03 ng/dL) was found in 59 patients (45%). Reduced cardiac function, which included reduced left or right ventricular systolic function, was found in 40 patients (28%). Reduced cardiac function was found in 18% of patients without troponin‐I elevation, 42% with mild troponin increase (0.04‐5.00 ng/dL) and 67% with significant troponin increase (>5 ng/dL). Reduced cardiac function was also present in more than half of the patients on mechanical ventilation or those deceased. The in‐hospital mortality of this cohort was 28% (N = 40). Using logistic regression analysis, we found that reduced cardiac function was associated with increased mortality with adjusted odds ratio  of 2.65 (1.18 to 5.96).Reduced cardiac function is highly prevalent among hospitalized COVID‐19 patients with biomarkers of myocardial injury and is independently associated with mortality. CADcoronary artery diseaseLVEFleft ventricular ejection fractionRVEFright ventricular ejection fraction1COVID‐19 is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). As of October 1, 2020, more than 34 million people worldwide became infected and over 1 million have died. The complex pathophysiology of COVID‐19, which includes cell death due to intracellular multiplication of virus, hypercoagulability, and cytokine storm2We performed a cohort study involving consecutive, laboratory confirmed COVID‐19 patients admitted to St. Francis Hospital, Roslyn, NY who underwent echocardiogram between March 1, 2020 and May 5, 2020. A waiver for individual consent was approved by the Institutional Review Board to allow for retrospective case review. Patients' demographic data, clinical diagnoses, vital signs, laboratory results, electrocardiograms, echocardiogram and chest radiograph or chest computerized tomography were retrospectively collected from electronic medical records.All patients had a laboratory confirmed COVID‐19 diagnosis using the reverse transcriptase polymerase chain reaction (RT‐PCR) test . Unless otherwise specified, laboratory values are expressed continuously. When serial cardiac troponin‐I values were reported the peak value was selected for the analysis. The upper normal limit for cardiac troponin‐I was >0.03 ng/mL in our institution . Troponin‐I cutoffs of 0.04 to 5.00, and > 5.00 were also used for evaluation.2.1Echocardiograms were performed using Philips IE 33, Philips EPIQ 7 , or GE VIVID S70  scanners. Due to the highly contagious nature of SARS‐CoV‐2 infection, 54 (38%) studies were performed as limited exams, which included evaluation of biventricular function, color Doppler of the valves and tricuspid velocity when present and pericardial effusion. There was one case where image quality was limited for the evaluation of cardiac function although it was adequate for the assessment of pericardial effusion. Left and right ventricular systolic function were evaluated qualitatively. Left and right ventricular (RV) ejection fractions (EF) were estimated visually and considered reduced when <50%.The RV systolic pressure was estimated based on the velocity of tricuspid regurgitation jet if present using the simplified Bernoulli equation and adding the estimated right atrial pressure, which was assumed to be 8 mmHg if the inferior vena cava was not well visualized. There were 59 (41%) cases where tricuspid regurgitant velocity was assessed. Pulmonary hypertension was defined as having RV systolic pressure ≥ 35 mmHg with mild, moderate and severe disease corresponding to pressure 35 to 44 mmHg, 45 to 59 mmHg and ≥ 60 mmHg. Significant valvular abnormalities consisted of valvular stenosis or regurgitation ≥ moderate (2) in severity.2.2χWe examined associations between a diagnosis of abnormal cardiac function, clinical laboratory results and all‐cause mortality in the context of COVID‐19. Laboratory values, events, and diagnostic counts are presented as mean (SD), median (interquartile range) or frequency (percent) as appropriate for data type and distribution. Stratified analysis of patients with a past medical history of CAD  was conducted using 3P = .014). An ST‐T wave abnormality was found in 71 (50%) of 141 patients who had a 12‐lead ECG on file. It was also more prevalent in patients with CAD than those without .Between March 1, 2020 and May 5, 2020 there were 843 COVID‐19 cases hospitalized in St Francis Hospital, Roslyn, NY. Of those, 143 consecutive patients underwent echocardiography, and were selected as the subjects of the current study. The mean age was 67 ± 16 years, and 62% (N = 89) were male. The most common comorbidities were hypertension (69%) and CAD (30%) , chest pain or suspected acute coronary syndrome N = 26, 18%) and arrhythmia . Reduced LVEF was present in 24% (34 of 142) of the patients. Of those, two thirds had LVEF≤35% (N = 24)  for patients with no troponin elevation, mild troponin increase (0.04‐5.00 ng/dL) and significant troponin increase (>5 ng/dL), respectively. Reduced LV systolic function was more common in patients with CAD than those without . The difference was not present for RV dysfunction (P = .23).We compared the prevalence of having reduced cardiac function in subgroups Table . There wFigure  for patThe most common cardiovascular outcome included congestive heart failure 16%, N = 23), new onset of arrhythmia including atrial fibrillation and ventricular tachycardia , pulmonary embolism , acute coronary syndrome  and tamponade with subsequent emergent pericardiocentesis  (Table 3, new on4In this retrospective review of hospitalized COVID‐19 patients we found that reduced cardiac function is prevalent among those with biomarkers of cardiac injury. In addition, it is prevalent among deceased patients and those on mechanical ventilation. Lastly, reduced LV and RV function are among the most important cardiac predictors of death in addition to older age, elevated troponin and elevated D‐dimer.Myocardial injury marked by the increase in troponin has been observed in hospitalized COVID‐19 patients.The prevalence of troponin elevation is 45% in our cohort, which is higher than previous reports.The exact cause of troponin elevation remains unknown in COVID‐19 patients. However, several proposed mechanisms appear plausible including acute coronary syndrome, myocarditis, direct cell injury from cytokine storm and thromboembolism due to hypercoagulability.In severe COVID‐19 cases, hypoxia and respiratory failure are common which often result in intubation and mechanical respiratory support. Unfortunately, the fatalities are extremely high among patients supported by a ventilator.The data from the current study should be interpreted within the context of several limitations. Bias is inevitable in selecting patients for an echocardiogram in this clinical cohort. Weighing the risk, clinicians are always mindful when ordering an echocardiogram for COVID‐19 patients. Therefore, patients who underwent the exam were more likely to have either a cardiac history or cardiac manifestations. Nevertheless, our findings are still highly relevant to the understanding of cardiac involvement in hospitalized COVID‐19 patients. In addition, due to lack of prior records, we are not able to fully differentiate prevalent from incident cardiac function abnormalities. Regardless, we found that the presence of reduced cardiac function has added vulnerability to COVID‐19 patients. It has also contributed significantly to the mortality of COVID‐19 patients. We recognize that the echocardiogram evaluation is likely incomplete in many cases especially for patients who were on mechanical ventilation which made the exam highly challenging. As a result, we may have underestimated the magnitude of cardiac abnormalities despite the high prevalence we have shown.In conclusion, reduced cardiac function is common among hospitalized COVID‐19 patients with biomarkers of cardiac injury, those on mechanical respiratory support, and those deceased. It is also an independent predictor of mortality in addition to older age, elevated troponin and increased D‐dimer.