Thrombolysis with tissue plasminogen activator (tPA) has been plagued by inadequate efficacy and a high risk of intracranial hemorrhage (ICH), which led to its replacement by procedures like percutaneous coronary intervention (PCI) whenever possible. Since this requires hospitalization, it is time-consuming, and compromising salvage of brain tissue and myocardium. Thrombolysis is the only first-line treatment that can provide sufficiently timely treatment for optimal recovery of organ function. However, for this potential to be realized, its efficacy and safety must be significantly improved over the current method. By adopting the sequential, synergistic fibrinolytic paradigm of the endogenous system, already verified by a clinical trial, this becomes possible. The endogenous system’s function is evidenced by the fibrinolytic product D-dimer that is invariably present in blood, and which increases >20-fold in the presence of thromboembolism. This system uses tPA to initiate lysis, which is then completed by the other fibrin-specific activator prourokinase (proUK). Since tPA and proUK in combination are synergistic in fibrinolysis, it helps explain their efficacy at their low endogenous concentrations.

A 78-year-old man, known case of, diabetes mellitus, and hypertension presented with fever, dry cough and dyspnea of five-day duration. He tested positive for SARS-CoV-2 infection and was admitted to the intensive care unit as a case of severe COVID -19 pneumonia. Evaluation revealed raised inflammatory markers CRP: 92.2 mg/ml, LDH: 556 IU/L, Ferritin: 286 ng/ml, D-dimer: 3716 ng/ml. On day 9 of illness, he developed numbness, pain and discoloration of right hand.

Introduction: The disease outbreak of COVID-19 has had a great clinical and microbiological impact in the last few months. In the preanalytical phase, the collection a sample from of a respiratory tract at the adequate moment and from the correct anatomical site is essential for a rapid and precise molecular diagnosis with a false negative rate of less than 20%. Materials and methods: We conducted a descriptive study of COVID-19 disease with a persistently negative RT-PCR test in patients seen at the National Institute of Respiratory Diseases (INER) in Mexico City in the period of March through May of 2020. 38 patients were registered with negative RT-PCR test obtained through nasopharyngeal and oropharyngeal swabbing. We evaluated the distribution of data with the Shapiro-Wilk test of normality. The non-parametric data are reported with median. The nominal and ordinal variables are presented as percentages. Results: The average age of our cohort was 46 years and 52.63% were male (n = 20). Diabetes Mellitus was documented in 34.21% (n = 13) of the patients, Systemic Hypertension in 21.05% (n = 8), Obesity in 31.57% (n = 12) and Overweight in 42.10% (n = 16). Exposure to tobacco smoke was reported in 47.36% (n = 18) of the patients. The median initial saturation of oxygen was 87% at room air. The severity of the disease on admission was: mild 71.05% (n = 27), moderate 21.05% (n = 8) and severe or critical in 7.89% (n = 3) of the cases respectively. 63.15% (n = 24) sought medical care after 6 or more days with symptoms. Lymphopenia was documented in 78.94% (n = 30). Median LDH at the time of admission was 300, being elevated in 63.15% (n = 24) of the cases. The initial tomographic imaging of the chest revealed predominantly ground glass pattern in 81.57% (n = 31) and predominantly consolidation in 18.42% (n = 7). The registered mortality was 15.78% (n = 6). Conclusion: Patients with COVID-19 and a persistently negative RT-PCR test with fatal outcomes did not differ from the rest of the COVID-19 population since they present with the same risk factors shared by the rest of patients like lymphopenia, comorbidities, elevation of D-Dimer and DHL on admission as well as a tomographic COVID-19 score of severe illness, however we could suggest that the percentage of patients with a mild form of the disease is higher in those with a persistently negative RT-PCR test.

The NIH has published treatment guidelines for treating COVID-19 patients in the hospital. However, as of this writing, there are no established protocols for treating COVID-19 positive patients in primary care. Accordingly, this investigator has taken on the task of reviewing the medical literature to be able to propose evidence-based protocols for treating COVID-19 positive patients in primary care. The CDC is advising people to do nothing when they find out they are positive for COVID-19 unless they have symptoms. The evidence from the literature irrefutably shows COVID-19 infection evokes a massive and deadly hyperinflammatory response called the “Cytokine storm” and that Cytokine levels in the blood have a predictive value in identifying an impending Cytokine storm. With such data primary care providers can effectively lower Cytokine levels and prevent critical illness and death. Accordingly, this paper presents identification of the problem of not having standard practices in primary care for people who are positive for COVID-19 and not knowing who is at risk. Moreover, the evidence shows that knowing vitamin D levels and correcting deficiencies can go a long way in reducing Cytokine levels. Additionally, the literature review presents evidence that undeniably shows the stark possibility that many of the COVID-19 related deaths can be prevented by identifying who is at risk for the Cytokine storm and other complications and providing early treatment even before symptoms appear.

Pulmonary embolism (PE) is an age-related disorder which is potentially fatal, but frequently misdiagnosed. However, the true prevalence of pulmonary embolism is unknown. Inaccurate estimates of PE prevalence might, in part, be attributable to underrecognition of atypical presentations of this disorder. If true prevalence is unknown, the positive predictive values of both typical and atypical symptoms and signs of PE will be unreliable. The negative predictive value of those parameters will, likewise, be unreliable. The aim of this review is to make clinicians more aware of atypical manifestations of PE, thereby increasing the likelihood of correct diagnosis and, hence, ascertainment of the true prevalence of PE. The range of atypical manifestations was explored by a literature search, using MEDLINE from 1946 to February 2019, and EMBASE, from 1947 to February 2019, and Pubmed, from February 2014 to February 2019, using the search terms atypical, uncommon, unusual, pulmonary embolism, lung embolism, pulmonary thromboembolism. This search revealed atypical presenting features such as non pleuritic retrosternal pain, abdominal pain, atypical breathing patterns, pulmonary oedema, Dressler’s syndrome, atypical radiographic manifestations, atypical electrocardiographic features, manifestations associated with oxygen saturation of 95% or more, coexistence of acute myocardial infarction and pulmonary embolism, coexistence of thoracic aortic dissection and pulmonary embolism, neurological manifestations other than stroke, paradoxical embolism, acute venous thrombosis of atypical location, and pulmonary embolism with normal D-dimer levels.

Introduction: Acute kidney injury (AKI) is one of the complications associated with severe COVID-19 infection, and it can present in up to 20% to 40% of the cases; of these, approximately 20% will require renal replacement therapy (RRT). Objective: To establish clinical and laboratory characteristics in a group of patients from Colombia with COVID-19 infection and AKI that received intermittent and prolonged RRT with the GENIUS® 90 technology in between March and July 2020. Design: Cross-sectional study. Results: 78.9% of participants were men and 21.1% were women. The main comorbidities were the following: Hypertension (65.3%), diabetes mellitus (38.9%), obesity (26.3%), cancer (5.3%), Chronic obstructive pulmonary disease (11.6%), cardiovascular disease (23.2%), active smoking (11.6%). 33.7% had chronic kidney disease (CKD) in the average serum creatinine on admission was 4.4 mg/dl. The following inflammatory markers were elevated: C-reactive protein (CRP), d-dimer and ferritin (20.3 mg/dl, 931mcg/l and 1174 ng/ml, respectively). 63.5% of patients underwent sustained low-efficiency dialysis (SLED) (6 to 12 hours) and the rest of the patients (36.35%) underwent conventional hemodialysis (less than 4 hours). The mortality of the total patient sample was 36.9%, lower in patients with CKD than in patients with no previous renal disease history (18.7% and 40.1%, respectively). Conclusion: Renal complications are frequent in patients with severe COVID-19. The development of AKI could be an isolated prognostic marker associated with an increase in mortality in patients with COVID-19, and one of the options is intermittent and prolonged RRT with the GENIUS® 90 system.

Background: Intracerebral hemorrhage (ICH) is one of the most feared complications after brain tumor surgery. Despite several factors being considered to influence bleeding, an increasing number of clinical studies emphasize that hemostatic disorders, developed during surgical aggression and tumor status, could explain unexpected ICH. The objective of this prospective study was to evaluate the influence of perioperative D-dimer levels on ICH after brain tumor surgery. Methods: This prospective, observational, 18-month study, at a single third-level hospital, included all consecutive adults operated on brain tumors and postoperative stay in an intensive care unit. Three blood samples evaluated D-dimer levels (A-baseline, B-postoperative and C-24 hours after surgery). The normal range considered was 0-500ng/ml. ICH, as a primary outcome, was defined as bleeding that generates radiological signs of intracranial hypertension either by volume or by mass effect on the routine CT scan 24 hours after surgery. Other tumor features and hemostasis variables were analyzed. Chi-squared and Fisher’s exact test were used in the inferential analysis for qualitative variables and Wilcoxon and T-Test for quantitative ones. P-value < 0.05 was considered significant for a confidence interval of 95%. Results: A total of 109 patients operated on brain tumor surgery were finally included, 69 male (63,30%) and 40 female (36,70%), with a mean age of 54,60 ± 14,75 years. ICH was confirmed in 39 patients (35,78%). Their average of DDimer was A-1.526,70 ng/dl, B-1.061,88 ng/dl, and C-1.330,91 ng/dl (A p0.039, B p0,223 C p0.042, W-Wilcoxon test). The male group was also associated with ICH (p0,030 X2 test). Of those 39 patients with ICH, 30 in sample A (76,9%), 20 in sample B (51,28%) and 35 in sample C (89,74%) had a D-dimer > 500 ng/dl (p0,092, p1, p0,761 X2 test) and the relative risk of developing a postoperative hematoma in this patients was increased 0,36-fold presurgery, 0,25-fold postsurgery and 0,40-fold 24hours after surgery. D-dimer variation, had no statistical significance (p0,118, p0,195, p0,756 T-test). Platelets and prothrombin activity were associated with D-dimer levels only in sample A (p 0,02 and p 0,20, W Wilson). Conclusion: High levels of perioperative D-dimer could be considered a risk marker of ICH after brain tumor surgery. However, more studies would be worthwhile to confirm this association and develop primary prevention strategies for stroke. 

The SARS-CoV-2 pandemic is still ongoing. Previously, several studies have been conducted to investigate laboratory markers as a tool for severity assessment during COVID-19 infections. Biological markers such as Platelet count, D-dimer and IL-6, Lymphocytopenia and others have been used for assessment of severity in COVID-19 disease patients (infected by SARS-CoV-2 Alpha, Beta, Gamma, Delta, Epsilon, and other variants). We observed a significant drop in lymphocyte count among suspected SARS-CoV-2 clinical patients with symptoms of fever, running nose, breathing discomfort, cough, and others during Omicron and Centaurus variants spread in Pakistan. A multicenter, cross-sectional study was conducted from Jan 2021 to Aug 2022, on 118,561 subjects to evaluate hematological abnormalities among suspected patients. Of note, significantly decreased lymphocyte levels (lymphocytopenia) were observed among 43.05% of infected patients. Also, the levels of NA (39.03%), HGB (28.27%), MCV (22.62%), PLT (8.17%), and ALB (4.30%) were also reduced among infected patients. This suggests that lymphopenia can be used as an alternative, cost-effective, early diagnostic biomarker for clinical COVID-19 patients, even before the diagnosis via real-time PCR. In resource-limited countries, the current study is critical for policy-making strategic organizations for prioritizing lymphocytopenia-based screening (as an alternative, cost-effective diagnostic test) in clinical COVID-19 patients, before real-time PCR-based diagnosis.