To evaluate the feasibility of contrast-enhanced mammography (CEM)-guided biopsy at Hospital del Mar, a Spanish university hospital.We retrospectively reviewed all consecutive women with a suspicious enhancing finding eligible for CEM-guided biopsy, who were prospectively enrolled in a pre-marketing clinical validation and feasibility study (October 2019 to September 2021). CEM-guided biopsy is a stereotactic-based procedure that, by using intravenous iodinated contrast media administration and dual-energy acquisition, provides localisation of enhancing lesions. All the biopsies were performed using a vacuum-assisted device. We collected procedural characteristics (patient position and type of approach), and histopathological results. Feasibility endpoints included success , procedural time, number of scout acquisitions and complications.A total of 66 suspicious enhancing lesions  in 64 patients  were referred for CEM-guided biopsy in the study period. The success rate was 63/66 (95.4%). Amongst successful procedures, patients were most frequently seated  and the preferred approach was horizontal . Median total time per procedure was 15 min. Median number of acquisitions needed before targeting was 2 (range 1–4). Complications consisted of hematoma  and vasovagal reaction . At histology, the malignancy rate was 25/63 (39.7%).In this first patient series, CEM-guided breast biopsy was feasible, with success and complication rates similar to those previously reported for magnetic resonance guidance.CEM may be used to guide biopsy of enhancing lesions through a stereotactic-based procedure combined with intravenous iodinated contrast media administration and dual-energy acquisition.• In this first patient series (n = 64), the success rate of CEM-guided biopsy was above 95%, the only complications were hematoma (22.2%) and vasovagal reaction (3.2%), and median total time per procedure was 15 min.• CEM-guided biopsy is feasible and could potentially be a widely available biopsy technique for enhancing-only lesions.• The online version contains supplementary material available at 10.1007/s00330-022-09021-w. Breast biopsy can be guided by different imaging techniques. The preferred first-line modality is ultrasound (US) but when suspicious lesions, such as architectural distortions or calcifications, are not visible on US, stereotactic or digital breast tomosynthesis (DBT) guidance is used.enhancing-only’ lesions, magnetic resonance imaging (MRI) guidance has, to date, been the only option in percutaneous biopsy, if there is no correlating finding in conventional second-look examinations [Some breast lesions can be depicted only by imaging modalities able to detect tumour neoangiogenesis, visualised as suspicious contrast enhancement after the injection of intravenous contrast media . For theinations –5. HowevContrast-enhanced mammography (CEM) is an emerging imaging tool that, similar to MRI, allows visualisation of breast tumour neovascularisation , 7. The There is scarce information in the literature on enhancing-only lesions detected by CEM. Amongst 839 women who underwent CEM after a screening recall, 70 enhancing-only lesions were found in 65 (7.7%) women. Of these 70 lesions, 38 (54.3%) subsequently proved to be malignant .CEM guidance is possible due to a specific biopsy hardware add-on to the mammographic equipment, in addition to a dedicated software upgrade that applies the dual-energy acquisition to the stereotactic technique; currently, only one device is commercially available.Due to the above-mentioned similarities between the 2 techniques, it is reasonable to assume that CEM-guided biopsy may be a valid alternative to MRI guidance. The purpose of this study was to evaluate the feasibility of CEM-guided biopsy in terms of its success rate , procedure time and complication rate amongst the first described series of patients undergoing this procedure.ClinicalTrials.gov ID: NCT05250674). We included all consecutive adult women presenting with a clinical indication for CEM-guided breast biopsy and considered eligible for this procedure as per standard of care between October 2019 and September 2021. CEM-guided biopsy was clinically indicated for suspicious enhancing lesions, not reliably identified by other morphological breast imaging techniques, including ‘second-look’ US or FFDM. Exclusion criteria were contraindications to iodinated contrast media. The study was approved by the hospital ethics committee (protocol number 2019/8890) and all patients provided written informed consent. A pre-marketing version of the Pristina Serena Bright™ GE Healthcare system had been under clinical validation in this study since 2019. The system received CE mark and Food and Drug Administration (510k) pre-marketing notification [This was a retrospective review of a cohort prospectively enrolled in a pre-marketing clinical validation and feasibility study performed at Hospital del Mar, a university hospital in Barcelona, Spain , allowing the biopsy needle holder to be automatically positioned.At the end of the required 2-min interval, the patient is positioned, the area where the target lesion is expected to be found is centred on the compression paddle, and a dual-energy image is acquired at 0°. Once the inclusion of the enhancement in the scout image has been confirmed, a pair of dual-energy angled views is acquired at ± 15°. In each of the angled images, the target is identified and marked, so that the device can calculate the 3 location coordinates  than stereotactic acquisitions . At the Clinical data of the included patients and suspicious lesions were collected, including patient age, breast density, background parenchymal enhancement (BPE) and the size and type of enhancement of the target lesion. Breast density was visually assessed on the low-energy image of the diagnostic CEM according to breast composition categories of the American College of Radiology (ACR) BI-RADS® mammography lexicon  and collProcedural characteristics, i.e. patient position (seated/lying), the kind of approach  and needle gauge, were collected for each procedure.For successful procedures, we collected the histopathological results on the biopsy specimen, as well as the kind of treatment undergone by patients. For patients who underwent surgery, we collected the pathological results of the surgical specimen.To evaluate the feasibility of CEM-guided biopsy, various endpoints were taken into account.Procedural success was defined as the visualisation of the suspicious enhancing lesion during procedural CEM, allowing adequate targeting and sampling, together with post-procedure imaging showing biopsy changes at the site of the intended lesion and with the clip in place or nearby in sequential mammography. Other cases were classified as cancelled, when the enhancing lesion visible at diagnostic CEM was not visible on procedural CEM, leading to non-performance of biopsy and short-term interval follow-up. Biopsies were classified as unsuccessful when the enhancing lesion was less visible on all procedural CEM views, limiting proper target selection, but the biopsy could still be performed by using another reference and guidance.The success rate was calculated. Procedural time was registered, considering the time span from contrast administration to clip placement scout view, immediately prior to breast decompression. Moreover, the number of scout acquisitions needed to represent the enhancing target in the field of view was collected. The complication rate was calculated, including immediately visible hematomas, vasovagal reactions, allergic reactions and late complications such as hematomas or infection.For patients who underwent surgery or percutaneous VAE, the upgrade rate was calculated as the percentage of cases originally graded as B3 on the biopsy specimen, according to the NHS Breast Screening Programme pathology classification , 26, andFrom October 2019 to September 2021, 64 patients were referred for CEM-guided breast biopsy. Of these, 2 underwent 2 biopsies for 2 different suspicious lesions , making a total of 66 procedures Table . The medOf the 66 suspicious lesions with an indication for CEM-guided biopsy, the procedure was successful in 63 95.4%) lesions Table . For the% lesionsn = 52, 82.5%) and the preferred approach was horizontal . The median total time per procedure was 15 min. The number of acquisitions needed before the targeting was between 1 and 4 (median 2 acquisitions). In most procedures , no complications were registered. Self-limiting early hematomas were recorded in 14 (22.2%) patients and vasovagal reactions in 2 (3.2%). Late complications consisted of only moderate hematomas . No severe complications or allergic reactions were registered.As for the procedural characteristics of successful CEM-guided biopsies, the patients were most frequently seated (n = 10), DCIS (n = 7), a combination of IDC and DCIS (n = 1) and invasive lobular carcinoma (n = 7)  were B1 on biopsy specimen, 26 (41.3%) were B2 , 10 15.9%) were B3  and 25 (39.7%) were B5, including IDC , the success rate was above 95%. The preferred patient position was seated, and the preferred approach was horizontal. The median total time per procedure was 15 min, and the median number of acquisitions before the targeting was 2. The only complications were early or late hematoma (27%) and vasovagal reaction (3.2%).MRI-guided biopsy is a safe and accurate technique but requires experience and the localisation process can be laborious and time-consuming, with a reported median of 35–41 min for imaging time and room occupancy of around 60–70 min –31. OtheThe MRI-guided VAB success rate reported in the literature ranges from 87 to 98%, with some degree of procedure deferral due to absent enhancement or decreased visualisation –36. The In our case series, the malignancy rate at biopsy was almost 40%, falling within the range of the cancer detection rate reported in the literature for MRI-guided breast biopsy, ranging from 18 to 61% , 36, 41.The horizontal approach was preferred in our series. The use of a plane compressor paddle with the horizontal approach offers better image quality and target visualisation. Conversely, the use of a fenestrated compressor paddle, necessary for the vertical approach, may result in artefacts in recombined images, due to differences in compressed breast thickness. Similarly, vertical access also has implications in the pre-fire view as the anaesthesia and VAB needle itself may interfere with the original target Fig. .Fig. 6VThe main complications were hematomas and vasovagal reactions, occurring in rates similar to those reported in the literature for other upright mammography-guided procedures –46, i.e.A limitation of the present study is the lack of information on AGD, since it can be argued that the main drawback of CEM guidance is radiation exposure. It is plausible that levels of exposure are acceptable, since previous data on diagnostic CEM have shown that the radiation dose remains below the threshold set by the European guidelines for screening mammography , 47. In In conclusion, in this first series of patients, CEM-guided breast biopsy was a feasible technique that was easy to implement and perform and which showed good success and complication rates and short procedural time (15 min on average). Since CEM-guided breast biopsy has the potential to be an alternative to MRI-guided biopsy for enhancing-only lesions, further studies are needed to directly compare the 2 techniques in terms of patient preference and cost-effectiveness.ESM 1(DOCX 2356 kb)


Malaria burden among under-five children living in endemic areas of Yemen is largely unknown due to the lack of community-based studies. Therefore, this study determined the prevalence and risk factors associated with falciparum malaria among under-five children in rural communities of Al-Mahweet governorate, Yemen.Plasmodium falciparum and non-falciparum species using rapid diagnostic tests (RDTs), and duplicate Giemsa-stained thick and thin blood films were examined for malaria parasites. The density of asexual P. falciparum stages was also estimated. Data were then analysed, and the agreement between the results of thick-film microscopy and RDTs for diagnosing falciparum malaria was assessed using the kappa index. Statistical significance was set at a P-value of < 0.05.This community-based, cross-sectional study recruited 400 under-five children from two rural districts of Al-Mahweet governorate in December 2019. Demographic characteristics  and risk factors associated with malaria were collected through interviews with children’s caregivers using a structured questionnaire. Finger-prick blood was screened for Plasmodium falciparum was prevalent among 9.8% (95% CI 7.0–13.1) of under-five children in the rural communities of Al-Mahweet, with a median asexual parasite density of 763 ± 2606 parasites/μl of blood (range: 132–4280) and low-to-moderate parasitaemia levels. Approximately one-third of microscopy-confirmed cases were gametocyte carriers. Multivariable logistic regression analysis confirmed that age of three years or older , not sleeping under a mosquito net the previous night of the survey , sleeping outdoors at night , and absence of indoor residual spraying (IRS) during the last year  were the independent predictors of falciparum malaria among under-five children in the rural communities of Al-Mahweet. The observed percentage agreement between thick-film microscopy and RDTs was 98.5%, with a very good agreement (k-index = 0.9) between the two methods for falciparum malaria diagnosis that was statistically significant.P. falciparum based on microscopy and RDTs. Age of three years or older, not sleeping under mosquito nets, sleeping outdoors at night and absence of IRS can independently predict falciparum malaria among them. The very good agreement between thick-film microscopy and RDTs for diagnosing falciparum malaria in children supports the usefulness of using RDTs in such resource-limited rural communities.Approximately one in ten under-five children in rural communities of Al-Mahweet is infected with  Plasmodium falciparum [Malaria is a major public health problem in the world. According to the latest report by the World Health Organization (WHO), 241 million cases were estimated in 85 malaria-endemic countries, increasing from 227 million in 2019 [Under-five children are at high risk of contracting malaria and developing severe disease . Apart fP. falciparum in the mid-2000s, and falciparum malaria was recently reported among 8% of schoolchildren from Bajil district of Hodeidah governorate [In Yemen, community-based malaria prevalence in under-five children is largely unknown, with few published studies reporting on childhood malaria. In this regard, 18.6% of children in rural districts of Taiz governorate were confirmed to be infected with ernorate . Anotherernorate . With thernorate , childreA community-based, cross-sectional study was conducted among under-five children in two rural districts of Al-Mahweet governorate known to be highly endemic for malaria in December 2019. Children of both genders were included in the study if they were residents in the study districts over the year preceding the study and did not receive antimalarial drug(s) one month before the study, and if their parents/guardians gave written informed consent.2 and is inhabited by approximately 597,000 people [, P. falciparum was detected among 15.6% (3235/20764) of febrile patients examined by RDTs and/or microscopy at health facilities in the two districts; of whom, 908/5001 (18.2%) were under-five children according to the data derived from the Electronic Disease Early Warning System (eDEWS) of Yemen . Therefore, these two districts were purposively selected to conduct this study.Al-Mahweet is a small mountainous governorate at the coordinates of 15° 28′ N and 43° 32′ E, approximately 111 km to the northwest of Sana'a. It is about 2,382 km0 people . It is e0 people , Hodeida0 people . Of its www.OpenEpi.com) based on an expected prevalence of 13% [A minimum sample size of 348 children was calculated using OpenEpi software, Version 3.01  and risk factors associated with malaria were collected through face-to-face interviews with children’s caregivers using a structured questionnaire. Axillary temperature was measured using a thermometer. Children with a temperature of ≥ 37.5 °C were considered febrile. Blood drops were collected by finger prick for rapid malaria testing and preparing duplicate thick and thin blood films.P. falciparum and non-falciparum species using CareStart™ Malaria HRP2/pLDH (Pf/PAN) Combo RDTs , according to the manufacturer’s instructions. Such RDT kits are currently adopted by the NMCP for malaria diagnosis in the country. Thick and thin blood films were prepared, Giemsa-stained and examined microscopically using standard procedures [P. falciparum asexual stages against 200 leukocytes on thick blood films, assuming an average leukocyte count of 8000/µl of blood [Blood drops were screened for ocedures , 16. Thiof blood , 16. Thik) index, where the agreement was interpreted as poor (k < 0.20), fair (k = 0.20–0.40), moderate (k > 0.40–0.60), good (k > 0.60–0.80) or very good (k > 0.80) [P-value of < 0.05.Data were analysed using IBM SPSS Statistics, Version 23.0 . Categorical variables were expressed as frequencies and proportions, while continuous variables were expressed as the median and interquartile range (IQR) for non-normally distributed data. The prevalence of falciparum malaria was reported with its corresponding 95% confidence interval (CI), as determined by microscopy and/or RDTs. Univariate analysis with Pearson's chi-square or Fisher’s exact test was used to test the association of demographic and clinical characteristics as well as risk factors with falciparum malaria among under-five children, reporting the odds ratios (ORs) and corresponding 95% CIs of the associations. Multivariable logistic regression analysis was performed for significant factors in univariate analysis to identify the independent predictors of falciparum malaria among under-five children, together with their adjusted ORs (AORs) and corresponding 95% CIs. Agreement between the results of thick-film microscopy and RDTs for diagnosing falciparum malaria was assessed using the kappa ( > 0.80) . StatistThe majority of children included in this study were males (54.2%), aged three years or older (62.5%), with a median (IQR) age of 3 (2) years, and living in households of six members or more (63.5%). Most children’s fathers had primary education (37.0%) or were uneducated (37.0%) and were labourers (68.8%), while the majority of children’s mothers were uneducated (83.2%) and unemployed (99.2%) Table .Table 1CFalciparum malaria was prevalent among 9.8% (95% CI 7.0–13.1) of under-five children in rural communities of Al-Mahweet, where microscopy confirmed infection among 9.3% (95% CI 6.6–12.5) and RDTs were positive among 8.8% (95% CI 6.2–12.0) of children , with low and moderate parasitaemia levels being prevalent among 51.4% and 48.6% of infected children, respectively. Of children with falciparum malaria, 32.2% were gametocyte carriers (Table P < 0.001) than in younger children . In contrast, no significant association was observed between falciparum malaria and gender, household size, parental educational status, or parental employment status. Likewise, no significant association was observed between falciparum malaria and fever, sweating, chills, vomiting, or jaundice , sleeping outdoors at night , absence of indoor residual spraying (IRS) during the last year  were significantly associated with falciparum malaria among under-five children in Al-Mahweet governorate , not sleeping under a mosquito net the previous night of the survey , sleeping outdoors at night , and absence of IRS during the last year  were the independent predictors of falciparum malaria among under-five children in the rural communities of Al-Mahweet  between thick-film microscopy and RDTs for falciparum malaria diagnosis that was statistically significant  pandemic, the situation might be even worse as a result of the negative impact of the pandemic on the prevention and control of infectious diseases, including malaria. The prevalence of falciparum malaria among children in the present study is slightly higher than that (8%) recently reported among schoolchildren in Bajil district of Hodeidah [P. falciparum among children in two rural districts of Taiz in the mid-2000s [P. vivax among under-five children in the present study is consistent with the very low prevalence of less than 0.25% recently reported among schoolchildren in Bajil [The vision of the NMCP’s strategic plan was to make Yemen malaria-free by the end of 2018 [P. falciparum infection among children in the rural communities of Al-Mahweet for the true burden of infection to be uncovered. Compared to the present study, a higher prevalence was reported among under-five children in Tanzania (15.9% by RDTs) [The prevalence of falciparum malaria among under-five children in the present study is comparable to the microscopy-based prevalence of 11.7% reported among under-five children in southern highland Rwanda in community- and facility-based surveys . Nonetheby RDTs) , Uganda by RDTs) , sub-Sahby RDTs) , Nigeriaby RDTs)  and Malaby RDTs) . Howeverby RDTs) , 26.P. falciparum in the rural communities of Al-Mahweet poses a major challenge to malaria control and elimination efforts. This gametocyte reservoir may considerably contribute to the transmission of infection in the community [Gametocyte carriage by approximately one-third of under-five children with microscopically confirmed ommunity , 6, 27, ommunity . Becauseommunity . Howeverommunity , 31.P. falciparum in younger children could be partly explained by the greater care they are given, reducing their exposure to mosquito bites. Furthermore, age-related differences in infection of children with P. falciparum could be attributed, among other factors, to variations in acquired immunity, transmission intensity and seasonality [P. falciparum among under-five children in the present study could be explained by similar exposure patterns to mosquito bites among male and female children in rural communities. On the other hand, the non-significant association between the educational and employment status of fathers and mothers with falciparum malaria among under-five children is inconsistent with those reported for children infected with malaria in African countries [The independent prediction of falciparum malaria in children aged three years or older in the present study is consistent with those recently reported for under-five children in Rwanda, Uganda and Malawi , 21, 24 sonality , 33. Thesonality . Gender ountries , 34, 35.The absence of a significant association between fever or other clinical features and falciparum malaria among under-five children in the present study is inconsistent with the finding among schoolchildren in Hajr valley in Hadhramout , where fP. falciparum compared to those who did. Sleeping under mosquito nets was found to be significantly associated with reduced malaria prevalence among under-five children in African countries [Vector control through mass distribution of long-lasting insecticidal nets (LLINs) is one of the most important interventions to protect local communities at risk of malaria. In Yemen, LLINs were first introduced and distributed to pregnant women and under-five children in 2006 , and sinountries , 23, 24.ountries  and undeountries .P. falciparum compared to those living in sprayed households. The lack of IRS during the year preceding the survey independently predicted falciparum malaria among under-five children in Al-Mahweet rural communities, highlighting the need to assess the household coverage with IRS in targeted areas and take action accordingly. In agreement with the present study, lacking IRS was found to be significantly associated with a higher risk of malaria among Ugandan under-five children [In Yemen, IRS was scaled up as a vector control intervention in 2007 to reinforce efforts to control and eliminate malaria in endemic areas of the country . In the children . Combinichildren , and succhildren . Understchildren .P. falciparum among under-five children in the present study, with children sleeping outdoors being 4.4-fold more likely to have been infected compared to those sleeping indoors. Given that sleeping outside houses is a common practice in rural communities of malaria-endemic areas of the country because of the hot climate, understanding the exophilic/exophagic behaviours of mosquitoes would help prevent outdoor malaria transmission. Sleeping patterns in the community can affect vector-human contact and could significantly increase malaria transmission. Therefore, parents should be educated not to leave their children to sleep outdoors without using LLINs, particularly with the finding that none of the under-five children in the present study was reported to be protected with mosquito repellents. The absence of a significant association between residence close to water or garbage collections and infection of under-five children with P. falciparum in the present study could be attributed to the almost similar geographical and ecological aspects of rural areas. In contrast, residence near water collections was an independent predictor of falciparum malaria among schoolchildren in Bajil [Sleeping outdoors at night was an independent predictor of infection with in Bajil . In anotin Bajil .Given that the strongest risk factors of malaria in under-five children were related to malaria control measures rather than natural topographical or other reasons, there is a need to assess the factors negatively influencing the performance of the NMCP in implementing such interventions. With the great global emphasis on expanding the use of current malaria control interventions together with international funding for them, the strong association between malaria prevalence and poor malaria control measures should raise concerns about the status of malaria control in such rural districts. Accordingly, gaps in coverage, access and utilization of LLINs besides household coverage with IRS should be identified and addressed, considering the potential impact of armed conflicts and the humanitarian crisis on malaria control efforts.RDTs have become essential tools for malaria control and elimination in rural areas and primary healthcare settings, where microscopy is unavailable or impractical, by enabling immediate diagnosis and prompt treatment. The significant and very good agreement between thick-film microscopy and RDTs for diagnosing falciparum malaria among under-five children in rural communities of Al-Mahweet supports using RDTs in remote and rural areas of the governorate where electricity is unavailable. However, the difference between the results of microscopy and RDTs in six cases justifies the need to assess the sensitivity and specificity of RDTs, preferably compared to PCR. Apart from being time-consuming, the sensitivity of microscopy may overlook infections with low parasite densities and its specificity is affected by the individual capacities of microscopists , 45. AccThe present study is limited by adopting microscopy and RDTs for malaria diagnosis. As a result, overlooking sub-microscopic infections and false positivity of RDTs could not be ruled out. However, it provides preliminary data on the burden of malaria among under-five children in rural communities of Al-Mahweet. Another limitation could be introduced by the possible variations in cluster sizes because of having no information about the population size per cluster to adopt the probability proportional to size sampling approach. As a conservative approach, we used a sample design effect of 2.0 when calculating the sample size to account for the uneven distribution of the outcome in clusters. The findings of the present study can guide public health authorities in tailoring interventions to reduce malaria burden. Malaria prevalence among under-five children in the present study underscores the need for molecular surveillance of malaria among such an at-risk population to uncover the burden of sub-microscopic infections and develop appropriate elimination strategies accordingly.P. falciparum based on microscopy and RDTs. Age of three years or older, not sleeping under mosquito nets, sleeping outdoors at night and absence of IRS are the independent predictors of falciparum malaria among under-five children. The very good agreement between thick-film microscopy and RDTs for diagnosing falciparum malaria among children supports the usefulness of using RDTs in such resource-limited rural communities.Approximately one in ten under-five children in rural communities of Al-Mahweet is infected with


Large multicenter studies reporting on the association between the duration of broad-spectrum antimicrobial administration and the detection of multidrug-resistant (MDR) bacteria in the intensive care unit (ICU) are scarce. We evaluated the impact of broad-spectrum antimicrobial therapy for more than 72 h on the detection of MDR bacteria using the data from Japanese patients enrolled in the DIANA study.We analyzed the data of ICU patients in the DIANA study . Patients who received empirical antimicrobials were divided into a broad-spectrum antimicrobial group and a narrow-spectrum antimicrobial group, based on whether they received broad-spectrum antimicrobials for more or less than 72 h, respectively. Differences in patient characteristics, background of infectious diseases and empirical antimicrobial administration, and outcomes between the two groups were compared using the chi-square tests (Monte Carlo method) for categorical variables and the Mann–Whitney U-test for continuous variables. We also conducted a logistic regression analysis to investigate the factors associated with the detection of new MDR bacteria.p = 0.042). Logistic regression showed that broad-spectrum antimicrobial continuation for more than 72 h  and cerebrovascular comorbidity on ICU admission  were associated with the detection of new MDR bacteria.A total of 254 patients from 31 Japanese ICUs were included in the analysis, of whom 159 (62.6%) were included in the broad-spectrum antimicrobial group and 95 (37.4%) were included in the narrow-spectrum antimicrobial group. The detection of new MDR bacteria was significantly higher in the broad-spectrum antimicrobial group (11.9% vs. 4.2%, Among Japanese ICU patients treated with empirical antimicrobials, broad-spectrum antimicrobial usage for more than 72 h was associated with the increased detection of new MDR bacteria. Antimicrobial stewardship programs in ICUs should discourage the prolonged use of empirical broad-spectrum antimicrobial therapy.Trial registration ClinicalTrials.gov, NCT02920463, Registered 30 September 2016, https://clinicaltrials.gov/ct2/show/NCT02920463The online version contains supplementary material available at 10.1186/s13756-022-01146-3. Staphylococcus aureus (MRSA) ; fluoroquinolone-resistant Escherichia coli (41.4% in 2019 vs. the target of 25% or lower); or carbapenem-resistant Pseudomonas aeruginosa  [The emergence of drug-resistant bacteria is an urgent issue worldwide. As many as 28 million cases of drug-resistant bacterial infection and 35,000 deaths are reported per year in the United States, and large increases in the prevalence rate of community fecal extended-spectrum β-lactamase (ESBL) carriage have also been reported in other regions , 2. In JIn intensive care units (ICUs), broad-spectrum antimicrobials are widely used and there is a high incidence of drug-resistant bacterial infections in critically ill patients. The Extended Study on Prevalence of Infection in Intensive Care III, an international multicenter observational study, found that 54% of ICU patients had infectious diseases and that 70% of patients received antimicrobials [Clostridioides difficile infection might be reduced by early de-escalation of antipseudomonal β-lactams [Various attempts have been made to reduce antimicrobial usage in ICUs, including using procalcitonin to initiate or discontinue use of antimicrobials , 7, inte-lactams .The Determinants of Antimicrobial Use and De-escalation in Critical Care (DIANA) study was an international multicenter observational cohort study approved by the European Society of Intensive Care Medicine  that folIn the DIANA study, the definition of de-escalation was “to change the antimicrobial with the intention of the treating physician to narrow the antimicrobial spectrum.” Therefore, de-escalation and discontinuation of broad-spectrum antimicrobials are not synonymous. Furthermore, few studies to date have evaluated the association between the continuation of broad-spectrum antimicrobials and the detection of MDR bacteria in ICUs . TherefoThis multicenter, retrospective cohort study analyzed the data from Japanese participants in the DIANA study . In the Participants with inadequate data on the date of initiation or discontinuation of antimicrobials or inadequate data on the date of MDR bacteria detection after the initiation of empirical antimicrobials, and participants who died within 72 h after enrollment were excluded from the analysis.Patients were divided into a broad-spectrum antimicrobial group and a narrow-spectrum antimicrobial group. The broad-spectrum antimicrobial group included participants who had received at least one broad-spectrum antimicrobial, continued for at least 72 h after the initiation of empirical antimicrobials. Patients initiated on narrow-spectrum empirical antimicrobials in whom at least one broad-spectrum antimicrobial was subsequently added within 24 h and continued for at least 72 h were included in the broad-spectrum antimicrobial group. The remaining participants were assigned to the narrow-spectrum antimicrobial group Fig. .Fig. 1FlData on patient characteristics, background of infectious diseases, and empirical antimicrobials were collected for each patient. Patient characteristic variables included sex, age, disease categories  on ICU admission, ICU admission diagnosis , comorbidities , and severity of the condition on ICU admission . Background variables of infectious diseases included health care exposure, immunosuppression, MDR detection by day 2 of the empirical treatment initiation, infectious focus , septic shock, causative microbial identification, multiple bacterial identifications, bacteremia, need for source control, effective source control by day 3, the timing from the hospital admission to empirical antimicrobial initiation, and the timing from the ICU admission to empirical antimicrobial initiation. Empirical antimicrobial variables included the number of empirical antimicrobials administered, the category of the administered empirical antimicrobials, the duration of empirical antimicrobial administration, and inappropriate administration of empirical antimicrobials.The primary outcome was new detection of MDR bacteria. The decision on whether and when to take cultures after initiation of the empiric antimicrobials was at the discretion of the physician. Secondary outcomes included clinical cure on day 7, recurrence of infection (by day 28), ICU and in-hospital mortality (by day 28), number of ICU-free days (by day 28), duration of organ support in the ICU , number of hospital-free days (by day 28), and number of antimicrobial-free days (by day 28).The following definitions were used:Stenotrophomonas maltophilia, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp., or a pathogen resistant to 3 or more antimicrobial classes.Bacteria that produce ESBL or carbapenemase, Pseudomonas spp. or anti-MRSA activity , use of steroids , solid organ transplantation with immunosuppressant use, bone marrow transplantation with immunosuppressant use, chemotherapy in the year prior to enrollment, radiotherapy in the year prior to enrollment, autoimmune diseases with immunosuppressant use, or human immunodeficiency virus (HIV) infection.p-values < 0.05 were considered statistically significant.The broad-spectrum and narrow-spectrum antimicrobial groups were compared and the significance of differences between groups was assessed using chi-square tests (Monte Carlo method) or Fisher’s exact tests for categorical variables, and Mann–Whitney U-tests for continuous variables. Two-tailed A univariate analysis was performed using logistic regression to determine the influence of patient characteristics, background of infectious diseases, and empirical antimicrobial usage on the detection of new MDR bacteria and the results were reported as odds ratios (ORs) and 95% confidence intervals (CIs). All analyses were conducted using IBM SPSS Statistics version 24 .Of the 276 patients at 31 facilities enrolled in the DIANA study in Japan, 254 (92.0%) patients who met the inclusion criteria were included in the analysis. There were 159 patients (62.6%) in the broad-spectrum antimicrobial group and 95 patients (37.4%) in the narrow-spectrum antimicrobial group , SAPS , and SOFA  scores , incidence of septic shock , SOFA score on day 0 , and longer time from the hospital admission to the empirical antimicrobial initiation , antipseudomonal penicillin + β-lactamase inhibitors , and glycopeptides  (Table p < 0.001).Compared with the narrow-spectrum antimicrobial group, initiation of the following broad-spectrum antimicrobials was more frequent in the broad-spectrum antimicrobial group: carbapenems  Table . The durp = 0.042) (Table p = 0.011) and significantly fewer antimicrobial-free days by day 28  among the patients alive at day 28. The clinical cure at day 7, the recurrence of infection, the ICU mortality by day 28, and the in-hospital mortality by day 28 were not significantly different between the two groups.The detection of new MDR bacteria was significantly higher in the broad-spectrum antimicrobial group than in the narrow-spectrum antimicrobial group  Table . Comparep = 0.047) and cerebrovascular comorbidity on ICU admission  were associated with a significantly higher detection rate of new MDR bacteria. The other variables had no significant differences  and how well the ICU staff adhered to infection prevention and control measures. However, the new MDR bacteria detected as the primary outcome of this study were different species within each facility, with only one exception. In the facility where two cases of MRSA were detected, the isolates were cultured 3 months apart, ruling out the possibility of direct transmission, suggesting that environmental factors did not have an appreciable effect on the study results.In conclusion, there was a higher detection rate of new MDR bacteria in Japanese ICU patients in whom empirical broad-spectrum antimicrobials were administered for more than 72 h than in patients who received narrow-spectrum empirical antimicrobial therapy. More well-designed studies are needed to determine if interventions that restrict the administration of broad-spectrum antimicrobials to less than 72 h reduce the detection of new MDR organisms and/or the incidence of infections caused by MDR organisms, when microbiologically and clinically justified, without worsening patient clinical outcomes. These results provide important evidence for developing ASP interventions in critically ill populations.Additional file 1: Factors associated with the detection rate of new multidrug-resistant bacteria within 28 days after study enrollment. OR odds ratio. The result of the logistic regression analysis to investigate the factors associated with the detection rate of new multidrug-resistant bacteria within 28 days after study enrollment.


Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is an established diagnostic procedure for solid pancreatic mass. However, the diagnostic yield between fine-needle aspiration (FNA) and fine-needle biopsy (FNB) remains unclear. We aimed to evaluate and compare the diagnostic yields between FNA and FNB using conventional FNA and Franseen needles of the same size 22-gauge needle, in patients with solid pancreatic mass who underwent EUS-TA without rapid onsite cytopathology evaluation (ROSE).All cases of EUS-TA by FNA or FNB for solid pancreatic mass between January 2017 and October 2020 in a single-centre university hospital were retrospectively reviewed. All procedures were performed without an onsite cytologist. Before the endoscopist finished the procedure, macroscopic onsite evaluation (MOSE) was confirmed. The diagnostic yield and the average number of needle passes between FNB and FNA were then compared.n = 77; FNB, n = 74) with solid pancreatic mass detected by cross-sectional imaging underwent EUS-TA. The mean age was 62.3 ± 12.8 years, with 88 (58.3%) males. Age, sex, mass location, tumour size and disease stage from imaging were not significantly different between the two groups. The diagnostic performance was higher in EUS-FNB (94.6%) than in EUS-FNA (89.6%). The mean number of needle passes was clearly fewer in FNB than in FNA . The total procedure time was shorter in FNB (34.7 min) than in FNA (41 min). The adverse event rate between FNB and FNA was not significantly different.A total of 151 patients (FNA, The diagnostic yield of solid pancreatic mass was higher in FNB using the Franseen needle than in FNA using the conventional FNA needle in a centre where ROSE is unavailable, without serious adverse event. In addition, FNB had fewer needle passes and shorter total procedure time. Pancreatic cancer is known to be associated with an unfavourable prognosis as a delayed diagnosis is commonly encountered. Symptomatic pancreatic cancer patients are usually beyond curative treatment, and despite various treatment options for patients with advanced-stage pancreatic cancer, to date, the survival outcome had not been satisfactory high; therefore, early diagnosis and treatment of pancreatic cancer are necessary for longer survival , 2.Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has been the main diagnostic tool for solid pancreatic mass , 4. EUS-In Thailand, the limitation of EUS-TA is biopsy needle cost and the unavailability of ROSE generally. In this study, we aimed to compare the diagnostic yield between EUS-FNA and EUS-FNB utilizing the 3rd-generation biopsy needles, when the same needle size of 22 gauge was used in patients with solid pancreatic mass without ROSE. The average number of needle passes, the total procedure time and adverse events were also compared between these two groups.We conducted a retrospective cohort single-centre study, including patients with solid pancreatic mass who underwent EUS-TA between January 2017 and October 2020. Specifically, all procedures were performed at the Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, the only university hospital in Southern Thailand. The inclusion criteria were as follows: (1) evidence of the solid pancreatic mass confirmed by computed tomography (CT) scan or magnetic resonance imaging (MRI), (2) age at least 18 years, (3) technical success of EUS-FNA or EUS-FNB without ROSE and (4) no prior EUS-TA done. Patients who were scheduled to undergo EUS-TA but with uncorrectable coagulopathy or any other reasons which caused EUS-TA to be inoperable were, therefore, excluded. We identified eligible patients according to the inclusion and exclusion criteria from our registration database, and using the hospital’s medical electronic database, the patients’ and procedural data were collected.The study protocol was approved by the Faculty of Medicine Institutional Review Board. The informed consent for the study was waived as this is retrospective in nature. However, all patients provided informed consent for EUS-TA before the procedures started.The identification of solid pancreatic mass on CT or MRI was certified by experienced radiologists. In our centre, the routine practice for patients with solid pancreatic mass depends on attending physicians. Usually, authorized physicians  referred patients to advance endoscopists for tissue diagnosis before initiating systemic chemotherapy in unresectable patients or in patients with questionable diagnoses. However, the small solid pancreatic mass within resectable criteria may proceed to surgical resection without EUS-TA for tissue diagnosis.In this study, EUS was performed using a linear array echoendoscope  and ultrasound machine  under conscious sedation by four experienced endosonographers . All patients with their first-time experiences of FNA or FNB for tissue acquisition in solid pancreatic mass were included.The general protocol for EUS-TA was as follows: before the procedure, the cross-sectional abdominal imaging was reviewed; the solid pancreatic mass was then identified and confirmed by EUS. The decision to perform tissue acquisition technique (FNA or FNB) was at the discretion of the attending physicians: either needle type, the standard suction technique  or the stylet slow pull technique, with or without fanning method. There were many factors for the decision such as the small tumour size and some endoscopist preferred biopsy needle but aspiration needle was preferred in limited budget patients. The location for TA, transgastric or transduodenal approach, was based on the location of the mass and endoscopists’ decisions. The FNA needle was a 22-gauge EZ-Shot , whereas the FNB needle was a 22-gauge Franseen needle . The needle was moved backward and forward within the lesion for at least 15 strokes. ROSE was unavailable for this procedure for an entire period of the study.The tissue samples were expelled from the needle in a standardized manner. The stylet was firstly introduced at the tip of the needle to expel the tissue samples on the glass slide, followed by flushing the needle with air or normal saline to expel the retained tissue, which called the “touch and smear technique” .The gross tissue specimen was initially evaluated by an endoscopist for adequate tissue sample (white or yellowish tissue at least 2 mm). This procedure is defined as macroscopic onsite evaluation (MOSE). The core tissues were collected in 10% neutral buffered formalin, and the smear glass slide was fixed in 95% alcohol solution for cytology.The procedure-related data  were recorded into the Endo Smart programme. Finally, glass slides and core tissue samples were sent to the hospital’s Anatomical Pathology Center, where they were reviewed by an experienced cytopathologist.All tissue samples of eligible patients were reviewed by a single experienced pathologist who was blinded to the procedural detail. The pathological results of ‘positive for adenocarcinoma or adenocarcinoma or carcinoma’ were considered adenocarcinoma. The pathological results of ‘suspicious for malignancy’ were then reviewed by two pathologists for final decision making whether they should be categorized as malignancy or not. The results of a specific diagnosis, such as lymphoma, tuberculosis or neuroendocrine tumour, were also reviewed. However, the definite diagnosis of mass-forming chronic pancreatitis was difficult to attain; it required not only a pathological result indicating fibrosis or chronic inflammation without malignant cell suspicion, but also cross-sectional imaging compatible with chronic pancreatitis and a stable clinical condition without evidence of malignancy on interval cross-sectional imaging after 6 months of follow-up. Meanwhile, the pathological results of unremarkable pancreatic tissue, nonpancreatic elements, atypical pancreatitis or acute pancreatitis were identified as non-diagnostic.In patients with pancreatic cancer, the disease staging and surgical resectability criteria were applied by The American Joint Committee on Cancer (AJCC) cancer staging manual 8th edition and TNM staging .After eligible patients were identified from the endoscopic centre’s database, we collected the following demographic and clinical characteristics: age; sex; tumour location; CT or MRI results; initial laboratory data; ECOG status; procedural data ; pathological report, final diagnosis and disease stage by (AJCC) 8th edition if pancreatic cancer was diagnosed; and diagnosis yield using the hospital’s medical electronic database.t-test for normally distributed data, whereas the categorical data were compared using the chi-square test or Fisher’s exact test. A p-value of < 0.05 was considered statistically significant. All statistical analyses were performed using the R programme .The patients were categorized into EUS-FNA and EUS-FNB groups. The comparisons of continuous variables between the two groups were analysed using Wilcoxon for non-normally distributed data and Student’s During the study period, there were 183 patients who underwent EUS-TA; of those, a total of 151 patients whose EUS-TA was technical successfully performed using 22-G needles were eligible and included in this analysis , although the study was non-randomized and retrospectively collected, the number of patients in the two groups were similar: 77 in the EUS-FNA group and 74 in EUS-FNB group. Table p=0.289). The solid pancreatic masses were mostly located in the pancreatic head in both groups . Given that most tumours were in the pancreatic head, the transduodenal approach was used in approximately two-thirds of the patients. Table p < 0.001). The mean number of needle passes was also significantly different, as the patients in the FNB group required a lower number of needle passes .As mentioned in Table The EUS-TA tissue sample was initially evaluated by an endoscopist for tissue adequacy (white or yellow tissue at least 2 mm) before being sent to the pathologist. The appropriate tissue sampling was reported by a pathologist; the FNB group had a significantly higher rate of tissue adequacy (100%) than the FNA group (74%) as shown in Table The definite diagnoses of solid pancreatic masses after EUS-TA are also shown in Table Non-malignant tumour, mass-forming chronic pancreatitis and tuberculosis were found in descending order. In patients with pancreatic adenocarcinoma, the cancer staging according to the AJCC 8th criteria is also reported in Table Interestingly, there were 4 cases of metastasis cancer in the FNB group in which core tissue samples played a major role in aiding the diagnosis; there were one case of metastatic melanoma and three cases of metastasis adenocarcinoma of the lung which could be diagnosed by specific immunohistochemistry.p = 0.146). The location of the pancreatic mass was not associated with the diagnostic yield following EUS-TA.In subgroup analysis according to the tumour size of not exceeding 4 cm and larger Table , we founThe pathological diagnosis of solid pancreatic mass has a crucial role in achieving a definite diagnosis and providing proper management, especially in an early stage, which correlates with prognosis in patients with cancer. Adequate tissue sampling might improve the diagnosis and avoid unnecessary surgery in some particular conditions, such as autoimmune pancreatitis, lymphoma and tuberculosis , 20, 21.p < 0.001), and the diagnostic yield was also higher in FNB than in FNA needle (94.6% vs. 89.6%); however, the statistically significant level was not reached. EUS-FNB using the 3rd-generation needle in our study was also associated with a shorter procedure time and fewer numbers of needle passes when compared with FNA significantly.In this study, we evaluated the diagnostic yield of EUS-TA by FNA versus FNB using the same size 22-G needles in a centre where ROSE is not available in patients with solid pancreatic mass lesion detect by cross-sectional imaging. We found that EUS-TA using the Franseen (Acquire) FNB needle had a significantly higher rate of tissue adequacy when compared with FNA needle  . In prevp = 0.146). Although it was statistically insignificant, it might be of clinical importance as the tumour size of 4 cm or smaller was one of the major resectable criteria in patients with pancreatic cancer.Nonetheless, in many limited-resource countries, onsite cytopathologists are not available, and ROSE is inevitably impractical, including in Thailand. We conducted this study to evaluate whether the 3rd-generation FNB needle provided a better diagnostic yield than FNA when the tissue acquisition was performed without ROSE. Our study illustrated that, in centre without onsite cytopathologist, the 3rd-generation Franseen FNB needle offered a significantly higher tissue adequacy for histopathological assessment and also achieved a higher diagnostic yield than the FNA needles, although the statistically significant level was not reached. The results of our study were also concordant with prior studies in terms of shorter procedure time and fewer needle-passed in the FNB group compared to the FNA group . MoreoveThe very high diagnostic yields of EUS-FNB in our study, over 90% in both mass sizes do of not exceeding 4 cm and over, might be explainable by the use of the 3rd-generation biopsy needle which was designed for harvesting a larger size of core tissue specimen, making it more feasible to evaluate tissue adequacy macroscopically onsite by endoscopists (MOSE). In addition, the endoscopists’ level of experience in our study may also play a role, as all endosonographers usually performed EUS-TA more than 50 cases/year during the entire study period.p < 0.001) or saving the total procedure time , EUS-FNB also provided better diagnostic performance than FNA, especially in tumour size of ≤ 4 cm, while the adverse events were comparable between the groups the same as in previous reports. The complication rate of EUS-FNA is approximately 1–2%, and the adverse event was comparable between the EUS-FNB and the EUS-FNA [Our study highlighted the benefits of EUS-FNB using 3rd-generation needles in solid pancreatic lesions over EUS-FNA in centres where ROSE was not available. Not only a lower number of needle passes (2.8 vs 3.7,  EUS-FNA , 31. The EUS-FNA . AlthougThis study was conducted in a tertiary university hospital and included patients with solid pancreatic mass initially assessed by cross-sectional imaging; the FNB and FNA groups had similar baseline characteristics. ROSE was unavailable in our centre, and this might be a pioneer study of a pragmatic setting of unavailable ROSE in many centres worldwide.Moreover, our study demonstrates the benefits of FNB in various aetiologies, such as tuberculosis, lymphoma and metastatic cancer which required core tissue or culture for a definite diagnosis. The limitation of this study is the retrospective design, and the subjects were commonly in the unresectable stage referred for tissue diagnosis before initiation of systemic chemotherapy. Although a better diagnostic yield was also observed in patients whose mass size ≤ 4 cm undergoing EUS-FNB, it is important to note that some patients who were considered to be resectable pancreatic cancer from cross-sectional imaging might proceed to curative surgery without pre-operative EUS-TA. Further studies in patients with solid pancreatic lesion size ≤ 4 cm are needed to confirm the benefit of EUS-FNB in comparison with EUS-FNA.The diagnostic yield of solid pancreatic mass was higher in FNB using the Franseen needle than FNA using the conventional FNA needle in a centre where ROSE is unavailable, without serious adverse event. In addition, FNB had fewer needle passes and shorter total procedure time.


In-person directly observed therapy (DOT) is standard of care for tuberculosis (TB) treatment adherence monitoring in the US, with increasing use of video-DOT (vDOT). In Minneapolis, vDOT became available in 2019.In this paper, we aimed to evaluate the use and effectiveness of vDOT in a program setting, including comparison of verified adherence among those receiving vDOT and in-person DOT. We also sought to understand the impact of COVID-19 on TB treatment adherence and technology adoption.We abstracted routinely collected data on individuals receiving therapy for TB in Minneapolis, MN, between September 2019 and June 2021. Our primary outcomes were to assess vDOT use and treatment adherence, defined as the proportion of prescribed doses (7 days per week) verified by observation (in person versus video-DOT), and to compare individuals receiving therapy in the pre–COVID-19 (before March 2020), and post–COVID-19 (after March 2020) periods; within the post–COVID-19 period, we evaluated early COVID-19 (March-August 2020), and intra–COVID-19 (after August 2020) periods.P=.001). The adoption of vDOT increased significantly from 35% (11/31) of patients with TB in the pre–COVID-19 period to 67% (12/18) in the post–COVID-19 period (P=.04). Consequently, overall verified  adherence among all patients with TB in the clinic improved across the study periods .Among 49 patients with TB , 18 (36.7%) received treatment during the post–COVID-19 period. Overall, verified adherence (proportion of observed doses) was significantly higher when using vDOT  compared to in-person DOT (mean 54.5%, SD 10.9; vDOT use increased after the COVID-19 period, was more effective than in-person DOT at verifying ingestion of prescribed treatment, and led to overall increased verified adherence in the clinic despite the onset of the COVID-19 pandemic. Tuberculosis (TB) remains a leading cause of infectious disease death globally and a contributor to morbidity and mortality in the United States -3. AdherDirectly observed therapy (DOT) has historically been regarded as the standard of care to document treatment adherence in most US public health TB clinics and involves a health care provider observing a patient take their TB medication ,9-11. ItWhile DOT offers the ability to document medication ingestion and couple adherence interventions , implementation may carry substantial inconvenience, cost, or stigma for patients and service providers -17. FurtRecent World Health Organization guidance has suggested that video directly observed therapy (vDOT) may replace DOT when video communication technology is available and can be appropriately administered, and its use has increased in US settings ,16. vDOTPrevious studies, including randomized trials, demonstrated either noninferiority of vDOT to DOT for verifying scheduled weekday doses, or found that a greater proportion of prescribed doses can be verified using vDOT under study conditions ,24-27. OWe sought to evaluate vDOT use and effectiveness in a clinic with no prior vDOT experience and to understand patterns of technology adoption since the onset of the COVID-19 pandemic. In the Hennepin County Minnesota Public Health Department, the standard of care for TB treatment monitoring before Sept 2019 involved in-person DOT, Monday to Friday; vDOT technology was subsequently made available for routine use at the discretion of the TB clinic. We assessed the initial implementation of vDOT into the clinic and characterized technology effectiveness and adoption over time through a prospective pragmatic implementation study, beginning in 2019 when vDOT became available.We conducted a pragmatic, prospective observational cohort study of TB treatment monitoring measured by self-report, in-person DOT, and asynchronous vDOT under routine conditions at the Hennepin County Public Health Clinic’s Tuberculosis Program in Minneapolis Minnesota, a setting without prior vDOT use or experience .Patients with signed disclosures and authorization for release of records in accordance with the Minnesota Health Records Act were included. Protocols were approved by the ethics committees at Johns Hopkins University, with reliance agreements established with Hennepin Healthcare Research Institute (IRB00174219).We abstracted routinely collected clinical data from electronic medical records for patients receiving treatment for active TB, who had signed disclosures and authorization for release of records in accordance with the Minnesota Health Records Act, from Sept 2019 to March 2021, with treatment follow-up available until June 2021 . We onlyAs part of routine care, the TB program individualizes the modality of TB treatment monitoring  using locally developed protocols and in accordance with Hennepin County Public Health Clinic guidelines, following a shared decision-making paradigm with patients . Local pMost patients with active TB were treated with standard therapy  7 days per week. Routine treatment monitoring for in-person DOT included a health care worker observing treatment ingestion at the patient’s home or agreed location during weekdays , with the exception of government holidays; other doses were self-administered, and adherence was determined by self-report.Patients using vDOT were instructed to submit videos documenting ingestion of medications according to their prescribed schedule , and were given initial training into the vDOT software including demonstrations and instructions . Patientverified adherence, defined as the proportion of total prescribed doses that were verified by in-person DOT or vDOT. Unobserved doses were considered either missed or “self-administered” if reported to be taken by the patient and documented as self-reported adherence in clinical charts  [t tests and chi-square tests to quantify the differences in clinical and demographic characteristics comparing in-person DOT and vDOT, at an alpha of .05 to determine statistical significance. We assessed the association of potentially relevant clinical and demographic factors with the receipt of vDOT using a multivariable logistic regression; covariates were included in the model based on clinical relevance to the outcome of interest . To evaluate vDOT use over time due to increased experience with the tool and to assess the impact of COVID-19, we divided the observation period into approximately 6-month increments: September 2019-February 2020 , March 2020-August 2020 (early COVID-19 period), and September 2020-March 2021 (intra–COVID-19 period); periods after March 2020 were the considered post–COVID-19 period. All analyses were conducted in STATA 16 (StataCorp).The “reach” or use of vDOT was defined as the proportion of patients in whom vDOT was used for treatment monitoring. We calculated effectiveness based on the itoring) ,20,24. WP=.02). Additional patient characteristics are shown in A total of 96 patients received treatment for active TB during the study period in the health department TB clinic, of which 49 (51%) signed disclosures allowing their charts to be abstracted for this study . Moreover, 96% (47/49) of the studied patients were non–US born, with the most commonly reported primary languages being English , Somali , Spanish , and Hmong  of patients, while the remainder  were monitored exclusively through in-person DOT . Among individuals initiating therapy after vDOT was available, the median time to start vDOT relative to TB treatment initiation date was 7 days (IQR 0-78). In-person DOT was initiated at the same time as treatment in the clinic . There was no difference in the overall treatment duration among those receiving vDOT  and those who did not receive vDOT .Overall, there was a trend toward increasing vDOT use when comparing each 6-month period, with 35% (11/31) using vDOT in the first 6 months after the technology became available , 64% (7/11) in the second 6 month (early COVID-19 period), and 71% (5/7) in the final (intra–COVID-19) period ; a larger proportion of women  received vDOT compared to men , but it was not statistically significant; no other clinical or demographic features, including race, English proficiency, alcohol use, site of TB disease, initial smear status, or drug resistance, were found to be associated with vDOT use. All patients successfully completed treatment irrespective of adherence monitoring modality (or were censored at the end of the study period).In univariate analysis , mean agverified adherence (proportion of prescribed doses verified through observation) was significantly higher when using vDOT , compared to in-person DOT . By contrast, few doses were documented as missed  when using in-person DOT; overall, among prescribed doses (7 days per week), a median of 1% (IQR 0-11) was documented as missed when using vDOT (P=.11).These findings were driven by the high proportion of “self-administered” doses when using in-person DOT  compared to periods when patients were using vDOT  and the natural process of technology adoption as staff became more familiar and comfortable with the platform. Our study setting implemented vDOT 7 days per week to allow the assessment of adherence to daily prescribed therapy; our study results may not be generalizable to clinics that prescribe treatment according to alternative dosing schedules .While self-report or pill counts, in-person DOT, vDOT, and other digital technologies  each provide a different level of certainty related to medication ingestion, they each broadly provide a measure of adherence. Our results add to the growing literature on the feasibility, acceptability, and effectiveness of video-DOT ,20,24,25Our results should be interpreted in the context of individualized decision-making as is advocated by current guidelines. Some individuals continued to receive in-person DOT based on tailored individual considerations; while our prior work has suggested that older age may be associated with a lower likelihood of initiating vDOT in other settings, we did not find specific clinical or demographic factors associated with vDOT selection in this clinic . We also


The exact pathogenesis of fibromyalgia (FM) syndrome is unclear. However, various infectious have been implicated with the development of FM after their acute phase. We aimed to investigate the incidence of FM syndrome among convalesced individuals following hospitalization for Acute Coronavirus Disease-2019 (COVID-19).We performed a cross-sectional study on patients who were discharged after COVID-19 hospitalization from the Sheba Medical Center, Israel, between July 2020 to November 2020. A phone interview was performed consisting of the following questionnaires: the Fibromyalgia Survey Diagnostic Criteria Questionnaire, Sense of Coherence Questionnaire to evaluate resilience, and the Subjective Traumatic Outlook Questionnaire to assess the associated psychological aspects of the trauma. The incidence of post-COVID FM was calculated and regression models were performed to identify predictors.The study population consisted of 198 eligible patients who completed the phone interview. The median age was 64 (52–72) and 37% were women. The median follow-up was 5.2 months (IQR 4.4–5.8). The incidence of FM was 15% (30 patients) and 87% (172 patients) had at least one FM-related symptom. Female gender was significantly associated with post-COVID FM . In addition, high median Subjective Traumatic Outlook scores and low median Sense of Coherence scores were both significantly associated with post-COVID FM .FM is highly prevalent among COVID-19 convalescent patients. Our finding suggests that a significant subjective traumatic experience and a low resilience are highly associated with post-COVID FM. Coronavirus Disease-2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) and was declared as a global pandemic in early 2020 by the World Health Organization ,4.Fibromyalgia (FM) syndrome is characterized by a chronic widespread musculoskeletal pain that frequently accompanied by fatigue, sleep, cognitive and mood disturbances . The preWe aimed to investigate the occurrence of the FM syndrome among convalesced individuals following hospitalization for Acute COVID-19 infection and to identify possible risk factors.We performed a cross-sectional study that included all patients above 18 years old that had been discharged between July 15, 2020, to November 15, 2020, from the COVID-19 wards at Sheba Medical Center, Israel. All subjects had a confirmed positive SARS-COV-2 Polymerase Chain Reaction (PCR) test during their hospitalization. We excluded patients who were discharged to nursing homes or healthcare facilities, patients with pre-infection cognitive impairment, patients with an active psychotic disorder, patients with a prior diagnosis of FM, patients with a preexisting active malignancy, and patients who passed away during follow-up. A phone interview was conducted for eligible patients between January 19, 2021, and April 5, 2021, in chronological order according to the date of discharge.The minimum interval time from discharge until the interview was 90 days. We retrieved from the electronic health record of Sheba Medical Center the demographic characteristics, medical history and the COVID-19 hospitalization details including severity, respiratory support, and the medications given. COVID-19 severity was classified, during the hospital stay according to the National Institutes of Health Criteria , rangingThis study was approved by the ethics committee of the Sheba Medical Center, Israel (7577-20-SMC). All study participants granted informed consent prior to their inclusion in the study.The phone interviewed included a series of questionnaires:According to the 2010 American College of Rheumatology (ACR) Diagnostic Criteria (Modified 2011), the clinical criteria are based on the Widespread Pain Index (WPI), which includes 19 pain sites, and the Symptom Severity Score (SSS), that ranges from 0 to 12 . This suTwo versions of the SOC scale were created by late Prof. Antonovsky. The first included 29 questions while the second included only 13 questions . Both scThe STO questionnaire was developed to assess individual differences in the way people subjectively perceive their trauma. Specifically, the STO is designed to evaluate the subject’s psychological condition prior to and following an event . The valThe interview included the three questionnaires and was administrated by an internist. The physician was trained and practiced for the SOC and STO questionnaires by a psychiatrist, and for the fibromyalgia survey questionnaire by a rheumatologist, both highly experienced in the field of fibromyalgia.Post-COVID patients with and without fibromyalgia criteria were compared. Categorical variables were reported as n (%), and continuous variables were reported as the median and interquartile range (IQR). Chi-square, Fisher’s exact, and the Wilcoxon signed-rank tests were used appropriately to compare between the groups. Logistic regression models were used to determine the odds ratio (OR) and the 95% confidence interval (CI) between the SOC and STO scores, and the presence of FM. The multivariate model was adjusted for gender and COVID severity due to assumed associations to the scores and FM. All tests were two-tailed, with p values < 0.05 considered to be statistically significant. Data analysis was performed using R version 4.1.1 .A total of 531 patients were discharged from the COVID-19 wards at Sheba Medical Center between July 15, 2020 to November 15, 2020, and 216 were excluded according to above mentioned criteria. In addition, 101 patients declined participation and 16 had a language barrier, leaving 198 patients who completed the phone interview and were thereby included in the study . The basCOVID-19 acute phase severity, length of hospitalization and treatment regimens during hospitalization were not found to be significantly associated with a post-COVID FM . Median Long-term consequences of COVID-19 have recently led to emerging research interests ,4, probaIn this study we have demonstrated that at five months following hospitalization for Acute COVID-19 infection, 15% of the patients and 26% of the women fulfilled the FM diagnostic criteria, approximately five times the proportion of FM in the Israeli general population . In addiSimilarly to our results, a recent study by Ursini et al. , based oIn our study, the median Subjective Traumatic Outlook score was 8 (IQR 5–14), and 73% of the FM group had a Subjective Traumatic Outlook score ≥ 13 compared with 22% in the non-FM group. Psychosocial and mental effects due to acute COVID-19 disease have been reported in a few previous studies. In one investigation, PTSD was observed in 22.2% of 185 COVID-19 convalesced patients almost one month after discharge, and female gender was significantly associated with PTSD development  . In anotM(r) = −.41). We suggest that poor resilience might be related to the pathogenesis of FM following Acute COVID-19 infection, and that poor resilience in FM patients may explain their relatively high prevalence of PTSD symptoms [A further interesting finding in our study is the significant correlation between a lower Sense of Coherence and the incidence of post-COVID FM . In a meta-analysis by Schäfer et al.  consistisymptoms .The current study is only the second one that investigated the occurrence of FM following Acute COVID-19 infection, and the first to have investigated occurrence of FM after hospitalization due to COVID-19 infection. This study is also the first investigation that attempts to predict the risk factors for developing FM following Acute COVID-19 infection.Our study has several limitations. Firstly, there was a relatively small number of participants, and there was no control group. Second, there was no baseline questionnaires recorded before our patients developed their Acute COVID-19 infection. Third, although this Fibromyalgia Survey Diagnostic Criteria Questionnaire has been previously validated and was found to have good reliability, convergence and discriminant validity , the FM Our findings suggest that Acute COVID-19 convalesced individuals have a higher proportion of FM compared to the general population. The presence of a female gender, low resilience and a significant subjective traumatic experience were found to be significantly associated with the occurrence of post-COVID FM.


Primary cardiac tumors (PCTs) are extremely rare entities. More than half of PCTs are benign, with myxoma being the most common tumor. Generally, simple tumor resection is the treatment of choice for benign PCTs since it has promising results that yield low complication and recurrence rates. However, in the COVID-19 pandemic era, the mitigation protocols and/or concurrent COVID-19 infection should be taken into account in patient management for the best overall outcome. To our knowledge, this is the first case report of a patient with a left atrial myxoma and systemic embolism complication in the form of an ischemic stroke, with a concurrent confirmed COVID-19 delta variant infection. CK: Creatine kinaseCK-MB: Creatine kinase – myocardial bandCPB: Cardiopulmonary bypassCRP: C-reactive proteinFDG-PET/CT: 8F-fluorodeoxyglucose positron emission tomography/computed tomographyGCS: Glasgow coma scaleHCU: High care unitICCU: Intensive cardiac care unitIVFD: Intravenous fluid dropsNSTEMI: Non ST-elevated myocardial infarctionPCT: Primary cardiac tumorSC: SubcutaneousTEE: Transoesophageal echocardiographyTTE: Transthoracic echocardiography Another study found that PCTs only account for around 0.3 – 0.7% of all cardiac tumors. Roughly 66.7% to 75% of all cardiac and pericardiac tumors are benign, while the rest are malignant. Out of all the PCTs, atrial myxoma is found to be the most common benign tumor,, while angiosarcoma is the most common malignant tumor., Approximately 70-75% of all cardiac tumors are myxomas, occurring predominantly in middle-aged females., They usually arise out of the fossa ovalis, and the most common place for myxomas to appear is the left atrium (75%), followed by the right atrium (18-23%) and the ventricles (2%) respectively., Although the clinical manifestations of cardiac myxomas are undefined since they are dependent on the size, location, and mobility of the tumor, patients with cardiac myxoma commonly have three main patterns of clinical presentation: haemodynamic consequences, systemic embolism, and constitutional manifestations., Although the gold standard for the diagnosis of PCTs requires histological examination, multimodality cardiac imaging has shown promising results., 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was found to have a sensitivity of over 90% in differentiating benign and malignant processes. Meanwhile, transthoracic echocardiography (TTE) and transoesophageal echocardiography (TEE) are suggested to have excellent sensitivity (95% and 100% sensitivity respectively) in detecting cardiac myxomas and differentiating it from thrombus or vegetation.,Primary cardiac tumors (PCTs) are an exceptionally rare abnormality. One study in the United States documenting autopsies found that the frequency of PCTs is around 0.02% (200 tumors in 1 million autopsies)., Moreover, while surgery is usually the treatment of choice in myxomas, a simultaneous COVID-19 co-infection complicates matters as operating fundamentals and post-operative managements need to be readjusted. These variables need to be taken into account to improve the patient’s prognosis. We present a patient with a left atrial myxoma and concurrent delta variant COVID-19 infection, in accordance with the CARE reporting checklist.In the COVID-19 pandemic era, physicians should take extra precautions in both conducting diagnostic tests and managing PCTs. Multiple guidelines have been published on how to perform cardiac imaging tests safely in the COVID-19 pandemic era for the benefit of both physicians and patients.A 36-year-old Indonesian female patient was admitted to the emergency department with an initial complaint of atypical chest pain with an onset of 11 hours prior to admission. The patient felt a piercing pain on both hemithoraces without radiation to the jaw or left arm. Additional complaints included fatigue and shortness of breath, which worsened with activity and when the patient was lying in the supine position. The shortness of breath alleviated when the patient rested or when the patient was sitting. Since one month prior to hospital admission, the patient had been having trouble breathing, especially at night, and had to sleep with two to three pillows to alleviate the shortness of breath. The patient had also been losing weight, as she lost around 5 kg in the last 90 days prior to hospital admission. Around 90 days prior to hospital admission, the patient suddenly passed out for around 30 minutes while walking, preceded by light-headedness and headache. Upon waking up the patient lost the ability to move her left arm and leg. The next day the patient regained some of her motoric strength but had experienced hemiparesis and diplopia ever since. The patient had no comorbidities and upon further inquiry revealed a family history of cardiovascular disease.9/L) and thrombocytosis (680 × 109/L), lowered serum calcium (7.4 mg/dL), increased fibrinogen levels (875 mg/dL), increased d-dimer levels , and increased C-reactive protein (CRP) levels (90.2 mg/L). Troponin T (<40 ng/L), Creatine Kinase (CK) (46 U/L), and Creatine Kinase-Myocardial Band (CK-MB) (15.6 U/L) was found to be normal. Blood gas analysis showed respiratory alkalosis, inadequately compensated . Chest x-ray taken on the upright position showed bilateral massive pleural effusion with bilateral lung oedema  of E4M6V5, a body temperature of 36.8C, a respiratory rate of 30×/min, a heart rate of 118×/min, a blood pressure of 90/60 mmHg, and a peripheral oxygen saturation of 99% with supplemental oxygen of 3 lpm delivered through nasal cannula. Physical examination on admission showed presence of S4 gallop on cardiac auscultation, decreased breathing sounds on both bases of the lungs and generalized rhales more prominent on the left medial posterior lung on lung auscultation, and pitting oedema on both lower extremities. Laboratory examination on admission showed leucocytosis , warm & wet acute decompensated heart failure, bilateral pleural effusion, ischemic stroke, and hypocalcaemia. The patient received emergency care and was then immediately moved to the intensive cardiac care unit (ICCU) for further care and examination. In the ICCU, the patient received intravenous fluid drops (IVFD) of furosemide 5 mg/hr, subcutaneous (SC) enoxaparin sodium 0.6 mL bid, aspirin 80 mg qd, clopidogrel 75 mg qd, atorvastatin 40 mg qd, and intravenous (IV) calcium gluconate 1 g qd. On the second day of hospitalization troponin T was tested again and found to be elevated (125 ng/L). Pulmonary ultrasonography was also conducted and pleural puncture was subsequently done and a total of 50 mL of fluid was obtained. On day three of hospitalization the patient was given a control rate bisoprolol of 2.5 mg qd and transthoracic echocardiography was conducted. We found an oval-shaped, pedunculated mass with a dimension of 3.3 cm × 7 cm on the left atrium extending through the mitral valve into the left ventricle .The diagnosis of left atrial mass, highly suspected of myxoma, was established and a median sternotomy to evacuate and evaluate the mass was set to be scheduled as soon as a thorough neurological examination was done to assess overall procedure risk. On day seven of hospitalization, there was an alteration in the patient’s mental status as the patient started speaking incoherently and could sometimes be heard speaking to herself. The diagnosis of organic mental disorder was suspected and haloperidol 0.5 mg bid was added to the therapy regimen. The patient also experienced fever (>38C) and the patient was then tested for COVID-19 using SARS-CoV-2 RT-PCR as it was also a part of the hospital’s pre-operation policy for the scheduled procedure. On day eight of hospitalization the SARS-CoV-2 RT-PCR came out positive and the patient was confirmed for COVID-19. Confirmatory genomic analysis was subsequently done as part of the hospital epidemiologic surveillance. The delta variant of SARS CoV-2 was confirmed within three working days.After the patient was confirmed for COVID-19, the pre-op assessment was halted and the patient was moved to the COVID-19 high care unit (HCU) to receive the standard therapy regimen for COVID-19. After twenty-two days, the COVID-19 infection resolved and the SARS-CoV-2 RT-PCR came out negative, the patient was re-evaluated for operation in order to evacuate the tumor, since the tumor had already shown signs and symptoms of obstruction. As soon as the septic marker and coagulation parameters were found to be within normal limits, the patient was scheduled for urgent operation. During anaesthetic induction, there was hemodynamic compromise, with elevated heart rate and supraventricular tachycardia (SVT). This unstable SVT occurred due to obstruction of the mitral valve. We were against cardioversion to prevent further embolization from the mass.The sternotomy and bicaval was performed urgently. Cardiopulmonary bypass (CPB) was initiated via ascending aorta and bicaval cannulation, then cardiac arrest was obtained with cardioplegic solution. Topical cardiac hypothermia was applied for cardiac protection during operation. We used the right pulmonary vein as venting. The pericardium was preserved for interatrial patch. The approach to evacuate the mass was from the right atrium. An incision was made in fossa ovalis, then the pedicle of the tumor was seen along with the mass. The mass was irregular, homogenous, brown-greyish coloured with a dimension of 8×7×6 cm. It was also fragile, had a soft consistency and multiple pedicles. After further evaluation, we saw that the right upper pulmonary vein was obstructed by the mass. The mass was evacuated completely and the right atrium chamber was washed with normal saline to prevent microemboli from tumor remnants.After evacuating the tumor, the mitral valve was evaluated with saline test and the result was remarkable, without any regurgitation or damage to the mitral valve leaflet. We did not perform mitral valve repair due to this finding. The interatrial septum was closed with pericardial patch due to the extensive mass extirpation. The CPB was weaned without any hemodynamic disturbances. Transoesophageal echocardiography was performed intraoperatively after the CPB was off, which showed trivial mitral regurgitation, mild aortic regurgitation, and no mitral valve regurgitation. Postoperative hemodynamic was unremarkable with low dose inotrope.The mass was sent to the pathology department for histologic examination, and it was confirmed that the left atrial mass was indeed a myxoma. The patient was subsequently discharged 6 days after the procedure with outpatient medications, all taken orally: atorvastatin tablet 20 mg once daily, digoxin tablet 0.25 mg once daily, omeprazole capsule 20 mg once daily, warfarin tablet 2 mg once daily, furosemide tablet 20 mg twice daily, and bisoprolol tablet 2.5 mg once daily. The patient was able to communicate adequately and perform daily tasks  with minimal assistance and without any neurological dysfunction post procedure.We present a middle-aged female with a left atrial mass highly suspected of myxoma and a subsequent concurrent delta variant COVID-19 infection confirmed a few days after hospitalization. To our knowledge, this is the first case report of a patient with a left atrial mass with a concurrent confirmed COVID-19 delta variant infection.,, The triad of clinical presentations of myxoma  as described by Karabiniset al. was also present in our patient in the form of dyspnoea, palpitations, congestive heart failure, fatigue, weight loss, and a history of cerebrovascular accident. In the case of cerebrovascular accidents, cardioembolic stroke in myxoma patients is a common phenomenon that usually happens in the middle cerebral artery. Alvarez-Sabínet al. reported 11 of 28 (39.3%) cardiac myxoma patients had embolic phenomena, six of which affected the cerebral arteries (54.5%). While our patient has regained some of her motoric strength, hemiparesis and diplopia are still present as of the writing of this paper. The neuroimaging exams’ results are still inconclusive. The patient’s progressively altered mental state could possibly be attributed to the evolution in size and/or location of the cerebral embolism. On the other hand, it is also probable that the systemic embolism in this patient is a case of COVID-19-associated thromboembolism, as COVID-19 patients are more predilected to develop thrombus due to their hypercoagulability.It is well documented that myxomas predominantly happen in females, more so in their productive years as we see in our patient., while TEE has better sensitivity (100%), than TTE and was considered, the idea was dropped due to COVID-19 restrictions as it is an aerosol-generating procedure.Using TTE, we found an oval-shaped mass with a dimension of 3.3 cm × 7 cm in the left atrium extending through the mitral valve into the left ventricle. The diagnosis of thrombus and vegetation should always be excluded first in diagnosing myxoma. TTE has excellent sensitivity in detecting myxomas (95%),, However, patients with a concurrent COVID-19 infection such as ours complicate matters. A study by Sanderset al. found that patients with COVID-19 undergoing cardiac surgery had a significantly higher mortality rate  and longer post-operative stay  than non-COVID patients. Taking into account the patient’s COVID-19 infection and her stable condition, we decided to delay the procedure after the COVID-19 resolution.Traditionally, simple tumor resection is the treatment of choice in patients with benign cardiac tumors such as myxoma, as the procedure has an excellent prognosis and is associated with low complications and recurrence rate.Another interesting fact that we would like to point out is the positive outcome of the patient’s SARS-CoV-2 RT-PCR test eight days after hospital admission even though the patient was admitted with a negative SARS-CoV-2 RT-PCR result, tested again for the second time on the subsequent day of hospitalization, which also came out negative. A summary of the patient’s SARS-CoV-2 RT-PCR tests is available inet al. studying all patients admitted to medical wards in two United Kingdom hospitals between 2 March and 3 May 2020 found that the real-life sensitivity of RT-PCR testing with nasopharyngeal specimens were only 83% when compared to the clinical reference in diagnosing COVID-19. Challenges in hospital resources and logistics are suspected to be the main reasons. The second possibility is a nosocomial infection of COVID-19. While hospitals around the world have generally established protocols to avoid nosocomial COVID-19 infection, avoiding it completely has proven to be a challenge as reported by Duet al. This case prompted the hospital to perform a thorough root cause analysis for its COVID-19 protocols to possibly improve the hospital’s prevention and control of infection.The first possibility is that the two initial SARS-CoV-2 RT-PCR results were false negatives. A study done by Gupta-WrightIn conclusion, although rare, patients admitted with haemodynamic compromise, systemic embolism, and constitutional manifestations should always be screened for cardiac tumors. TTE and TEE are excellent imaging modalities in detecting myxoma. Simple tumor resection is the treatment of choice for myxoma, but in the COVID-19 era, physicians should assess the risks and benefits more thoroughly while maintaining strict COVID protocols to get the best results while reducing the chance of nosocomial COVID-19 infection.The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013).Written informed consent was obtained from the patient for the publication of this case report and accompanying images.All data underlying the results are available as part of the article and no additional source data are required.SAN, EDT, MMA conceptualized and wrote the original draft of the article. EG, NDI, AP, MY, M, APS, MAP, CWP, IS, AFS, and LDL reviewed, wrote, and curated the data needed for the article. This is an interesting case about left atrial myxoma and concomitant delta variant COVID-19 infection. The authors provided detail history taking, physical examination, patient's progression, and comprehensive treatment. Histopathologic result of the resected mass was also provided. Epidemiology data and the outcome of cardiac surgery complicated by COVID-19 infection supported and explained the approach that was used by the authors.Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?YesIs the case presented with sufficient detail to be useful for other practitioners?YesIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?YesIs the background of the case’s history and progression described in sufficient detail?YesReviewer Expertise:Cardiovascular, critical care, and COVID-19I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Please add an intraoperative photo of cardiac myxoma.Please add some details about follow-up (1 or 2 or 3 months post-op)Can you provide a preoperative chest CT scan? Please find the interesting information about pneumonia in patients with COVID in below references: Ye Z, Zhang Y, Wang Y, Huang Z, Song B. Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review. Tenda ED, Yulianti M, Asaf MM, Yunus RE, Septiyanti W, Wulani V, Pitoyo CW, Rumende CM, Setiati S. The Importance of Chest CT Scan in COVID-19.How many days the patient stayed in the ICU?Thank you for your interesting report and your presentation. Some comments:Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?PartlyIs the case presented with sufficient detail to be useful for other practitioners?YesIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?YesIs the background of the case’s history and progression described in sufficient detail?YesReviewer Expertise:Cardiac SurgeryI confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.