Cancer treatment associated cardiac toxicities

Cardiovascular disease remains the leading cause of mortality and morbidity in men and women both in the US and worldwide. With increased access to healthcare, it is predicted that life expectancies in developed countries will continue to rise and thus, lead to an increase in both cardiovascular disease and cancer. Similarly, improved survival rates in cancer patients have led to an increased awareness of the presence and potential worsening of cardiovascular disease in these patients. Cardiovascular complications due to side effects from cancer therapy or from cancer progression can be a common occurrence. Although recent advances in cancer therapeutics have led to improved survival rates and quality of life, the increase in life expectancy may be counteracted by the increased morbidity and mortality from progressive cardiac pathology. Examples of such complications include local invasion or distant metastatic spread, which can lead to superior vena cava syndrome, cardiac tamponade, or hyperviscosity syndromes. In addition, many chemo and radiation therapies can be directly toxic to the cardiovascular system. This review aims to discuss the potential cardiac toxicities of the most commonly used chemotherapeutics along with some strategies to manage these complex patients

A study to know the various causes of pleural effusion and role of pleural fluid adenosine deaminase enzyme in tuberculous pleural effusion

Background: India has the maximum burden of both non MDR tuberculosis (TB) and Multidrug-Resistant (MDR) TB, as per data reported in Global TB Report 2018 and tuberculosis is remains one of the most common cause of pleural effusions.Methods: This was a cross-sectional study conducted in Department of Respiratory Diseases and a total of 110 patients with pleural effusion were included in the study, which were enrolled for treatment from July 2018 to June 2019.Results: One hundred and ten patients with pleural effusion were enrolled during the study period. There were 65 males (59%) and 45 (40.9%) females.  The overall mean age for males and females were 44.4±18.84 years (35-87 years) and 38.28±17.66 years (35-87 years) respectively. Tuberculous Pleural Effusion group (TPE) seen in 82 patients. Right sided pleural effusion (69.5 %) were more common than left sided (30.4 %). In TPE group the mean pleural fluid ADA level were 86.41±38.08 IU/L (range: 14-195 IU/L). The Malignant Pleural Effusion (MPE) group included 21 patients. In MPE group the mean pleural fluid ADA level were 34.10±32.88 IU/L (range: 8-144 IU/L). The difference in pleural fluid ADA levels between TPE and MPE group was statistically highly significant.Conclusions: Tuberculous pleural effusion was the most common cause of pleural effusion in present study and observed in 74.5% cases

Quantification of edema in edematous severe acute malnutrition children aged 6 months to 5 years

Background: Malnutrition is rampant in India, and edematous severe acute malnutrition (SAM) is associated with high morbidity and mortality. Clinical grading of edema in these children is known, but still, no quantification has been described. Objective: The objective of this study was to quantify the edema in children with edematous SAM (E-SAM). Materials and Methods: This prospective study was conducted over a period of 1 year in 2016 at a malnutrition treatment center of tertiary hospital attached to a medical college. 50 children were selected with E-SAM between 6 months and 5 years of age. The sick children, needing intensive care unit care and having edema other than nutritional cause, were excluded from the study. These children were examined daily for any change in the status of edema by comparing the change in the weight, which was taken using electronic weighing scale. The weight at which child has no edema and no fall in weight for 2 consecutive days was defined as dry weight of the child. All the children were evaluated regarding the onset of loss of edema, days taken for complete disappearance of edema, weight loss per day, mean loss of weight, etc. Results: Of 50 children with E-SAM, 28 were male and 22 were females. Mean age of children was 16.5±11.04 months. The admitted children had +2 edema (26%), followed by +3 edema (17%), while only 7 (14%) children had +1 edema. The mean age of moderate-to-severe edematous children was 13 months. These children started losing edema by day 3 (3.22±0.9) and the mean number of days for complete disappearance of edema was 10.02±2.8 days. The mean percent weight loss was 1% per day and did not vary with different grades of edema (p>0.5). The percentage loss of total weight was maximum for children with +3 edema being 13%, followed by 10% in +2, and 5% in +1 edema which was statistically significant (p=0.004). Conclusions: E-SAM children have grade +1, +2, and +3 edema which are equivalent to 5%, 10%, and >10% over to their actual weight, respectively, and younger children are more susceptible to moderate-to-severe edema

Machine Learning Applications in the Neuro ICU: A Solution to Big Data Mayhem?

The neurological ICU (neuro ICU) often suffers from significant limitations due to scarce resource availability for their neurocritical care patients. Neuro ICU patients require frequent neurological evaluations, continuous monitoring of various physiological parameters, frequent imaging, and routine lab testing. This amasses large amounts of data specific to each patient. Neuro ICU teams are often overburdened by the resulting complexity of data for each patient. Machine Learning algorithms (ML), are uniquely capable of interpreting high-dimensional datasets that are too difficult for humans to comprehend. Therefore, the application of ML in the neuro ICU could alleviate the burden of analyzing big datasets for each patient. This review serves to (1) briefly summarize ML and compare the different types of MLs, (2) review recent ML applications to improve neuro ICU management and (3) describe the future implications of ML to neuro ICU management

Intravenous doxycycline, azithromycin, or both for severe scrub typhus

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of −13.3 percentage points (95% confidence interval [CI], (21.6 to −5.1; P=0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of −14.8 percentage points (95% CI, −23.1 to −6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, −7.0 to 10.0; P=0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry–India number, CTRI/2018/08/015159.

Combination therapy in hypertension: An update

Meticulous control of blood pressure is required in patients with hypertension to produce the maximum reduction in clinical cardiovascular end points, especially in patients with comorbidities like diabetes mellitus where more aggressive blood pressure lowering might be beneficial. Recent clinical trials suggest that the approach of using monotherapy for the control of hypertension is not likely to be successful in most patients. Combination therapy may be theoretically favored by the fact that multiple factors contribute to hypertension, and achieving control of blood pressure with single agent acting through one particular mechanism may not be possible. Regimens can either be fixed dose combinations or drugs added sequentially one after other. Combining the drugs makes them available in a convenient dosing format, lower the dose of individual component, thus, reducing the side effects and improving compliance. Classes of antihypertensive agents which have been commonly used are angiotensin receptor blockers, thiazide diuretics, beta and alpha blockers, calcium antagonists and angiotensin-converting enzyme inhibitors. Thiazide diuretics and calcium channel blockers are effective, as well as combinations that include renin-angiotensin-aldosterone system blockers, in reducing BP. The majority of currently available fixed-dose combinations are diuretic-based. Combinations may be individualized according to the presence of comorbidities like diabetes mellitus, chronic renal failure, heart failure, thyroid disorders and for special population groups like elderly and pregnant females

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research