Top 5 barriers in cardiac arrest research as perceived by international early career researchers - A consensus study.

Aim of the study: Cardiac arrest research has not received as much scientific attention as research on other topics. Here, we aimed to identify cardiac arrest research barriers from the perspective of an international group of early career researchers. Methods: Attendees of the 2022 international masterclass on cardiac arrest registry research accompanied the Global Out-of-Hospital Cardiac Arrest Registry collaborative meeting in Utstein, Norway, and used an adapted hybrid nominal group technique to obtain a diverse and comprehensive perspective. Barriers were identified using a web-based questionnaire and discussed and ranked during an in-person follow-up meeting. After each response was discussed and clarified, barriers were categorized and ranked over two rounds. Each participant scored these from 1 (least significant) to 5 (most significant). Results: Nine participants generated 36 responses, forming seven overall categories of cardiac arrest research barriers. "Allocated research time" was ranked first in both rounds. "Scientific environment", including appropriate mentorship and support systems, ranked second in the final ranking. "Resources", including funding and infrastructure, ranked third. "Access to and availability of cardiac arrest research data" was the fourth-ranked barrier. This included data from the cardiac arrest registries, medical devices, and clinical studies. Finally, "uniqueness" was the fifth-ranked barrier. This included ethical issues, patient recruitment challenges, and unique characteristics of cardiac arrest. Conclusion: By identifying cardiac arrest research barriers and suggesting solutions, this study may act as a tool for stakeholders to focus on helping early career researchers overcome these barriers, thus paving the road for future research.

Takotsubo Syndrome in Black Americans: Insights From the National Inpatient Sample.

BACKGROUND: Data on race-related differences in the clinical outcomes of Takotsubo syndrome are limited, particularly for Black patients. This study aimed to assess whether race and sex may have an additional impact on the inpatient mortality of patients with Takotsubo syndrome. METHODS: A total of 4,628 patients from the United States' National Inpatient Sample from 2012 to 2016 were identified; propensity score analysis revealed a similar propensity score between Black patients (n = 2,314) and White patients (n = 2,314), which was used to balance observed covariates. Sex and age distributions were identical between the 2 groups. The groups were also similar in baseline characteristics, including cardiovascular risk factors. White patients were compared with Black patients on in-hospital outcomes and inpatient mortality. A logistic regression analysis was conducted to measure the difference in mortality based on race and sex. RESULTS: Compared with White patients, Black patients had a higher percentage of in-hospital complications, including cerebrovascular accidents (4.9% vs 2.5%, P ≤ .01), acute kidney injury (25% vs 19%, P ≤ .01); longer lengths of stay (8 vs 7 days, P ≤ .01); and higher inpatient mortality (6.1% vs 4.5%, P < .01). When analysis was conducted with race and sex combined, inpatient mortality was higher among Black men than among White women (odds ratio, 2.7 [95% CI, 1.80-3.95]; P ≤ .01). CONCLUSION: This study showed that Black patients with Takotsubo syndrome have higher in-hospital complications and inpatient mortality rates. When race and sex were combined, inpatient mortality was significantly higher among Black men than among either White men and women or Black women.

Peri-operative chemotherapy versus preoperative chemoradiotherapy in treatment of gastro-oesophageal junctional adenocarcinomas: A 10-year cohort study.

BACKGROUND: Gastro-oesophageal junctional (GOJ) cancers have been, more latterly, considered a distinct tumor entity with characteristic genetic profiles. The optimal multimodal therapy of advanced GOJ cancers remains debatable. In this comparative study, we analyzed the outcomes of peri-operative chemotherapy (CT) versus pre-operative chemoradiotherapy (CRT) in treatment of advanced GOJ adenocarcinomas. METHODS: This study included patients with locally advanced but resectable GOJ adenocarcinomas who underwent surgical resection after oncological therapy between 2010 till 2019 at our institution. Follow up to May 2021 was completed. The outcomes between CT and CRT groups were retrospectively analyzed. The long-term follow up data was obtained via direct contact with the patients during oncological clinics, cross-checked with hospital/national patients' electronic databases. RESULTS: 107 patients had GOJ cancers; 90 (84%) patients met our inclusion criteria. Perioperative chemotherapy was administrated in 65 (72%) patients. Overall median survival rate was 2.2 years in CRT-group compared to 2.4 years in CT-group (p-value 0.29), with comparable recurrence rates (48% vs 36% respectively). R0-resections were higher in CRT-group (84%) compared to CT-group (71%), yet insignificant p-value 0.197. Preoperative chemoradiotherapy achieved higher complete pathological response (28% vs 6%, p-value 0.009) and negative lymph nodes rates (64% vs 37%, p-value 0.014) compared to CT-group. Short-term outcomes (postoperative complications, morbidity rates and length of hospital stay) were similar across both groups. CONCLUSION: Preoperative chemoradiotherapy was associated with higher complete pathological response and negative lymph nodes rates for GOJ adenocarcinomas compared to peri-operative chemotherapy, without an increase in postoperative complications or morbidity rates. However, it wasn't associated with improved overall or disease-free survival rates.

Age-sex effect on in-hospital complications and mortality in patients with Takotsubo syndrome. Insights from the National Inpatient Sample.

Age and sex differences in Takotsubo syndrome (TTS) are still a matter of debate. The present study aimed to evaluate the difference in cardiovascular (CV) risk factors, CV disease, in-hospital complications, and death within different sex-age groups. Using the National Inpatient Sample database between 2012 and 2016, 32,474 patients older than 18 years of age hospitalized with the primary diagnosis of TTS were identified. A total of 32,474 patients were enrolled; 27,611 (85.04%) were female. CV risk factors were higher in females, while CV diseases and in-hospital complications were significantly higher in males. The mortality in males was twice as high as that of female patients (9.83% versus 4.58%, p<0.01), and in the logistic regression model after adjustment for confounders, the odds ratio (OR) was 1.79, the confidence interval was 1.60-2.02, and p<0.01. After dividing the group based on age, in-hospital complications were inversely related to age in both sexes, and the length of in-hospital stay was double in the youngest group compared to the oldest one. Mortality increased progressively with age in both groups but was constantly higher in males for each age group. Multiple logistic regression analysis for mortality was performed for the two sexes separately and for the three age groups, considering the youngest one as the reference group. In females, the OR was 1.59 and 2.88, respectively, for groups 2 and 3; for males, the OR was 1.92 and 3.15, all of them statistically significant (p<0.01). In-hospital complications were more common in younger patients with TTS, particularly in males. Mortality was positively correlated with age for both sexes, but mortality was higher in males compared to females in all age groups.

Contemporary review on pediatric hypertrophic cardiomyopathy: insights into detection and management.

Hypertrophic cardiomyopathy is the most common genetic cardiac disorder and is defined by the presence of left ventricular (LV) hypertrophy in the absence of a condition capable of producing such a magnitude of hypertrophy. Over the past decade, guidelines on the screening, diagnostic, and management protocols of pediatric primary (i.e., sarcomeric) HCM have undergone significant revisions. Important revisions include changes to the appropriate screening age, the role of cardiac MRI (CMR) in HCM diagnosis, and the introduction of individualized pediatric SCD risk assessment models like HCM Risk-kids and PRIMaCY. This review explores open uncertainties in pediatric HCM that merit further attention, such as the divergent American and European recommendations on CMR use in HCM screening and diagnosis, the need for incorporating key genetic and imaging parameters into HCM-Risk Kids and PRIMaCY, the best method of quantifying myocardial fibrosis and its prognostic utility in SCD prediction for pediatric HCM, devising appropriate genotype- and phenotype-based exercise recommendations, and use of heart failure medications that can reverse cardiac remodeling in pediatric HCM.

SARS-CoV-2 epitopes inform future vaccination strategies.

All currently approved COVID-19 vaccines utilize the spike protein as their immunogen. SARS-CoV-2 variants of concern (VOCs) contain mutations in the spike protein, enabling them to escape infection- and vaccination-induced immune responses to cause reinfection. New vaccines are hence being researched intensively. Studying SARS-CoV-2 epitopes is essential for vaccine design, as identifying targets of broadly neutralizing antibody responses and immunodominant T-cell epitopes reveal candidates for inclusion in next-generation COVID-19 vaccines. We summarize the major studies which have reported on SARS-CoV-2 antibody and T-cell epitopes thus far. These results suggest that a future of pan-coronavirus vaccines, which not only protect against SARS-CoV-2 but numerous other coronaviruses, may be possible. The T-cell epitopes of SARS-CoV-2 have gotten less attention than neutralizing antibody epitopes but may provide new strategies to control SARS-CoV-2 infection. T-cells target many SARS-CoV-2 antigens other than spike, recognizing numerous epitopes within these antigens, thereby limiting the chance of immune escape by VOCs that mainly possess spike protein mutations. Therefore, augmenting vaccination-induced T-cell responses against SARS-CoV-2 may provide adequate protection despite broad antibody escape by VOCs.

Three-dimensional printing in integrated multi-modality imaging approach for management of prosthetic valves infective endocarditis.

After heart failure, infectious endocarditis is the second leading cause of death in patients with prosthetic valves. Aortic pseudoaneurysms are a serious complication of infective endocarditis in mechanical or bioprosthetic aortic prostheses. Diagnostic and management challenges are posed by aortic pseudoaneurysms. In these cases, a multi-modality imaging approach with a heart team is recommended. We described two cases of aortic pseudoaneurysms that developed as a result of infective endocarditis. The first case involved a TAVI patient who developed infective endocarditis as a result of diabetic foot complications. Because traditional echocardiography and computed tomography failed to show the anatomy of the lesion, we used 3D printing to show the anatomy, extension of the pseudoaneurysm, and proximity to the right coronary artery. The second case involved a patient who underwent Bentall's surgery with an aortic root and mechanical aortic valve and later developed infective endocarditis complicated by pseudoaneurysms. In this case, 3D printing was used for preoperative surgical planning.

Muscle oxygenation during normoxic and hypoxic cycling exercise in humans with high-affinity haemoglobin.

NEW FINDINGS: What is the central question of this study? Do humans with high-affinity haemoglobin (HAH) demonstrate attenuated skeletal muscle deoxygenation during normoxic and hypoxic exercise? What is the main finding and its importance? Examination of near-infrared spectroscopy-derived muscle oxygenation profiles suggests that fractional oxygen extraction is blunted during hypoxic exercise in humans with HAH compared with control subjects. However, muscle tissue oxygen saturation levels were higher in humans with HAH during exercise in normoxia compared with control subjects. These alterations in fractional oxygen extraction in humans with HAH might influence blood flow regulation and exercise capacity during hypoxia. ABSTRACT: Recently, researchers in our laboratory have shown that humans with genetic mutations resulting in high-affinity haemoglobin (HAH) demonstrate better maintained aerobic capacity and peak power output during hypoxic exercise versus normoxic exercise in comparison to humans with normal-affinity haemoglobin. However, the influence of HAH on tissue oxygenation within exercising muscle during normoxia and hypoxia is unknown. Therefore, we examined near-infrared spectroscopy-derived oxygenation profiles of the vastus lateralis during graded cycling exercise in normoxia and hypoxia among humans with HAH (n = 5) and control subjects with normal-affinity haemoglobin (n = 12). The HAH group elicited a blunted increase of deoxygenated haemoglobin + myoglobin during hypoxic exercise compared with the control group (P = 0.03), suggesting reduced fractional oxygen extraction in the HAH group. In addition, the HAH group maintained a higher level of muscle tissue oxygen saturation during normoxic exercise (HAH, 75 ± 4% vs. controls, 65 ± 3%, P = 0.049) and there were no differences between groups in muscle tissue oxygen saturation during hypoxic exercise (HAH, 68 ± 3% vs. controls, 68 ± 2%, P = 0.943). Overall, our results suggest that humans with HAH might demonstrate divergent patterns of fractional oxygen extraction during hypoxic exercise and elevated muscle tissue oxygenation during normoxic exercise compared with control subjects.

Radiologic Diagnosis of Nasal Gliomas with an Illustrative Case Report.

Nasal gliomas are congenital masses of dysplastic neuroglial and fibrovascular tissue. However, other congenital nasal masses, including encephaloceles, hemangiomas, and dermoid cysts make clinical diagnosis difficult. Radiological examination is imperative to accurate diagnosis of nasal gliomas. We hereby present the diagnostic imaging features of these lesions, which necessitate inclusion into the differential diagnosis of a congenital nasal mass.

Dasatinib-Induced Nephrotic Syndrome: A Case Report.

Second-generation tyrosine kinase inhibitors (TKI), such as nilotinib and dasatinib, are used in the first-line treatment of chronic myeloid leukemia (CML), usually after the failure or resistance to imatinib. Despite a good safety profile, medications in this category have an increased incidence of specific adverse events such as pulmonary hypertension, pleural effusion, and cardiovascular/peripheral arterial events. However, renal complications are rarely reported and observed. We herein report a case of a 46-year-old patient with CML who developed nephrotic syndrome upon switching from imatinib to dasatinib therapy, with the resolution of symptoms upon treatment discontinuation and switching to nilotinib. Limited cases were reported in the literature. It is thought that the inhibition of the vascular endothelial growth factor (VEGF) pathway is the main mechanism leading to proteinuria. Dasatinib-induced nephrotic syndrome should be looked for as it can be resolved by either reducing the dose or stopping it altogether and switching to another TKI.

A complex unit for a complex disease: the HCM-Family Unit.

Hypertrophic cardiomyopathy (HCM) is a group of heterogeneous disorders that are most commonly passed on in a heritable manner. It is a relatively rare disease around the globe, but due to increased rates of consanguinity within the Kingdom of Saudi Arabia, we speculate a high incidence of undiagnosed cases. The aim of this paper is to elucidate a systematic approach in dealing with HCM patients and since HCM has variable presentation, we have summarized differentials for diagnosis and how different subtypes and genes can have an impact on the clinical picture, management and prognosis. Moreover, we propose a referral multi-disciplinary team HCM-Family Unit in Saudi Arabia and an integrated role in a network between King Faisal Hospital and Inherited and Rare Cardiovascular Disease Unit-Monaldi Hospital, Italy (among the 24 excellence centers of the European Reference Network (ERN) GUARD-Heart).   Graphical Abstract.

Stabilization of hypoxia-inducible factor ameliorates glomerular injury sensitization after tubulointerstitial injury.

Previously, we found that mild tubulointerstitial injury sensitizes glomeruli to subsequent injury. Here, we evaluated whether stabilization of hypoxia-inducible factor-α (HIF-α), a key regulator of tissue response to hypoxia, ameliorates tubulointerstitial injury and impact on subsequent glomerular injury. Nep25 mice, which express the human CD25 receptor on podocytes under control of the nephrin promotor and develop glomerulosclerosis when a specific toxin is administered were used. Tubulointerstitial injury, evident by week two, was induced by folic acid, and mice were treated with an HIF stabilizer, dimethyloxalylglycine or vehicle from week three to six. Uninephrectomy at week six assessed tubulointerstitial fibrosis. Glomerular injury was induced by podocyte toxin at week seven, and mice were sacrificed ten days later. At week six tubular injury markers normalized but with patchy collagen I and interstitial fibrosis. Pimonidazole staining, a hypoxia marker, was increased by folic acid treatment compared to vehicle while dimethyloxalylglycine stimulated HIF-2α expression and attenuated tubulointerstitial hypoxia. The hematocrit was increased by dimethyloxalylglycine along with downstream effectors of HIF. Tubular epithelial cell injury, inflammation and interstitial fibrosis were improved after dimethyloxalylglycine, with further reduced mortality, interstitial fibrosis, and glomerulosclerosis induced by specific podocyte injury. Thus, our findings indicate that hypoxia contributes to tubular injury and consequent sensitization of glomeruli to injury. Hence, restoring HIFs may blunt this adverse crosstalk of tubules to glomeruli.

Relapse of Diabetes After Roux-en-Y Gastric Bypass for Patients With Obesity: 12 Years Follow-up Study.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is a recommended treatment for type 2 diabetes mellitus (T2DM) in patients with obesity, with superiority over medical therapy. While diabetes remission is achieved initially in 60-90% of patients following surgery, many may experience relapse of diabetes on the long-term. Data on long-term follow-up of bariatric surgery is scarce. We report this 12-year follow-up study of glycaemic control following RYGB. METHODS: Two hundred seventeen patients with obesity (109 diabetic, 108 matched nondiabetic) who underwent RYGB between 2000 and 2008 were identified. Data was recorded prospectively for these patients at baseline and 2 years postoperatively. The long-term data was obtained via direct contact with the patients cross-checked with our hospital/national patients' electronic databases. RESULTS: The follow-up rate was 88% (initial age 44 ± 9 years, female 79%). The mean (± SD) percentage total weight loss was 28% (± 15%) and 27% (± 17%) at 2 years and 12 years, respectively. Diabetes remission rate was 69% at 2 years, but decreased to 36% at 12 years following surgery. The 12-year incidence of new-onset T2DM in the control group was 4.3%. On univariate analysis, age, preoperative duration of diabetes and use of insulin were associated with less chance of diabetes remission at long-term (p value 0.06, 0.01 and 0.03, respectively). However, on multivariate regression analysis, only the duration of diabetes preoperatively remained significant (p = 0.025). CONCLUSION: This study shows a high relapse of diabetes 12-year post-RYGB despite the durability of weight loss. This affects preoperative counselling and indicates a need for a longer follow-up to detect relapse.

A new tailored protocol based on laparoscopy in the management of abdominal shotgun injuries: a case-series study.

PURPOSE: Abdominal shotgun injuries derive their significance from the wide range of injuries they cause. The management of this type of injury has been continuously evolving. Despite the ongoing incorporation of laparoscopy in management of abdominal trauma, there is no definite protocol raising the role of laparoscopy in such injuries. In this study, we outlined a tailored protocol in the management of penetrating abdominal shotgun injuries differing from the previous protocols which comprised either mandatory exploration or non-operative management. PATIENTS AND METHODS: This case-series study included patients who attended to our emergency department with a shotgun injury involving the abdomen between December 2014 and October 2016. Only stable patients with no clinical signs of surgical abdomen, in combination with CT evidence of penetrating intra-abdominal pellets, were subjected to laparoscopic exploration in this study. RESULTS: Thirty patients fulfilled the inclusion criteria. During laparoscopy, ten patients were designated as positive for injuries. No missed injuries were identified. Two of the cases identified as positive by laparoscopy needed no further management while the remaining eight patients warranted laparotomy. Only one of these eight patients turned out to have a non-therapeutic exploration. Consequently, laparoscopy in the management of these injuries had an overall accuracy of 96.7%, sensitivity of 100%, specificity of 95.7%, positive predictive value of 87.5% and negative predictive value of 100% with highly significant p value < 0.001. CONCLUSION: A tailored protocol relying on the use of laparoscopy in the management of stable patients with CT evidence of penetrating abdominal shotgun injuries is safe and helps to cut down the number of non-therapeutic laparotomies with consequent decrease of complications.