Ulinastatin Add-on to Standard of Care in Critically Ill COVID-19 Patients: A Multicenter, Retrospective Study

Aim: To assess the impact on 30-day mortality with ulinastatin (ULI) used as add-on to standard of care (SOC) compared to SOC alone in coronavirus disease (COVID-19) patients requiring admission to the intensive care unit (ICU). Materials and methods: In this multicentric, retrospective study, we collected data on clinical, laboratory, and outcome parameters in patients with COVID-19. Thirty-day mortality outcome was compared among patients treated with SOC alone and ULI used as add-on to SOC. Odds ratio (OR) and 95% confidence intervals (CI) were determined to identify the predictors of 30-day mortality. Results: Ninety-four patients were identified and enrolled in both groups with comparable baseline parameters. On univariate analysis, 30-day mortality was significantly lower in ULI plus SOC group than SOC alone group (36.2 vs 51.1%, OR 0.54, 95% CI 0.30–0.97, p = 0.040). The effect on mortality was more pronounced in patients who did not require intubation (10.9 vs 34.0%, OR 0.24, 95% CI 0.09–0.66, p = 0.006) and with early administration (within 72 hours of admission) of ULI (30.7 vs 57.9%, OR 0.32, 95% CI 0.11–0.91, p = 0.032). On multivariate analysis, only intubation predicted mortality (adjusted OR 10.13, 95% CI 3.77–27.25, p<0.0001) and the effect of ULI on survival was not significant (adjusted OR 0.58, 95% CI 0.22–1.52, p = 0.270). Conclusion: Given the limited options for COVID-19 patients treated in ICU, early administration of ULI may be helpful, especially in patients not requiring intubation to improve the outcomes. Further, a large, randomized study is warranted to confirm these findings.

Retrospective Cohort Observational Study to compare the Effect of Mycobacterium w along with Standard of Care vs Standard of Care alone in critically ill COVID-19 Patients

Background: COVID-19 has created enormous health crisis in India due to limited available treatments. Majority of the physicians use sepsis as a prototype to understand the pathophysiology of COVID-19 as there are similarities. Heat-killed Mycobacterium w (Mw) (Inj. Mw®) is a known immunomodulator, which is approved for the treatment of gram-negative sepsis. This observational study was aimed to evaluate the role of Mw along with standard of care (SOC) in critically ill COVID-19 patients. Methods: Total 448 patients’ data (intervention group: 298 in Mw plus SOC vs 150 in SOC alone) with reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed critically ill COVID-19 patients who were admitted at five tertiary care centers were evaluated. They were observed for changes in laboratory [C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase (LDH), and interleukin-6 (IL-6)] parameters, hospital stay, intensive care unit (ICU) stay, and discharge status after giving 0.3 mL intradermal Mw for 3 consecutive days along with SOC during hospitalization. Standard of care included injectable steroids, remdesivir, and heparin. Data were analyzed using STATA 14.2 (StataCorp., College Station, Texas, USA). Results: In baseline characteristics, Mw plus SOC arm had more critically ill patients as seen by higher high-resolution computed tomography (HRCT) score, higher lab values [CRP, ferritin, D-dimer, LDH, creatinine, alanine aminotransferase (ALT)], and more oxygen requirement as compared to SOC alone. Mycobacterium w arm had significantly higher mortality rate in ICU and hospital. Both hospital stay and ICU stay were longer in Mw arm. However, subgroup analysis found that early initiation of Mw (<3 days vs >3 days) was associated with significantly lesser odds of mortality and lesser odds of intubation requirement. Early initiation of Mw (<3 days vs >3 days) also resulted in significantly lesser duration of stay in the ICU along with reduction of CRP, D-dimer, and LDH. Moreover, further analysis of early initiation of Mw (<3 days vs control) resulted in significant reduction in lab values (procalcitonin, CRP, ferritin, LDH, and D-dimer). Conclusion: Mw when added to SOC was found to associate with significantly increased risk of mortality and increased length of hospital stay. However, time since admission to administration of Mw was a significant predictor of in-ICU deaths in multivariate analysis. Early initiation of Mw (<3 days) was observed to be a protective factor against ICU deaths from the multivariate logistic regression model. However, large randomized controlled trials are required to support the same.

The Current Status of Prostate Cancer

Prostate cancer (PC) is the commonest malignancy in men that causes significant morbidity and mortality. The incidence has quadrupled in the last three decades. This is predominantly due to its increased detection by excellent newer techniques like Prostate-specific antigen (PSA) evaluation, Transrectal ultrasonography (TRUS), Transrectal ultrasound-guided biopsy, Contrast enhanced ultra sound studies, Multiparametric (Mp) MRI (MpMRI) and Nuclear medicine. Its incidence shows a rise in India. With the availability of PSAand trans-rectal biopsy, nowadays the majority of prostate cancers (PC) are diagnosed at an asymptomatic early stage (T1). Most PC are adenocarcinomas while a small percentage are ductal carcinomas, mucinous carcinomas, signet ring cell carcinomas and small cell carcinomas. These variants have poor prognosis. The anatomy of prostate will help us to further understand the basis of TRUS studies. The whole prostate can be divided into Transition Zone (TZ),Central Zone (CZ) and Peripheral Zone (PZ). This zonal anatomy of prostate is vital to understand the PC, since PC is predominantly seen as follows: TZ – 20%; CZ – 10%; and PZ – 70%. PSAis an extremely valuable tool in the evaluation of PC. It is exclusively produced by the prostate and to a lesser extent by the seminal vesicles. It is present in all post-pubertal men and absent in women and men following radical prostatectomy. Though the PSA is a vital parameter to detect PC, it can also be elevated in: i) Benign prostrate hypertrophy; ii) Prostate inflammation; iii) Prostatic infarct; iv) Postdigital rectal examination; and v) Sexual activity. The normal value of PSA is 0-4 ng/mL. The two techniques that are available to assess PSA levels are polyclonal assay or monoclonal assay. The monoclonal assay is the most commonly used method the world over. The accepted PSA values are: <4ng/mL (normal); 4.0-10.00ng/mL (borderline) and >10 ng/mL (abnormal). Other than normal PSA values, there are other PSA parameters which are often useful in confirming the diagnosis of PC. These are: i) PSAdensity; ii) PSAvelocity; iii) PSAdoubling time; iv) Other markers like PCA3; and v) PC is associated with more protein bound PSA(less free PSA) than in BPH. Free PSA (FPSA) can enhance the specificity of the total PSA value for detection of the PC while reducing the number of unnecessary biopsies. Another new finding is that of levels of insulin like growth factor binding protein-2 (IGFBP-2) appear to be directly associated with the presence of PC.

Duxorubicin-induced cardiotoxicity.

The survival rate of cancer patients has greatly increased over the last 20 years. However, to achieve this result, a considerable price has been paid in terms of the side-effects associated with the intensive anticancer treatment. Cardiotoxicity of anticancer drugs is a serious problem. It is defined, by the National Cancer Institute, as the “toxicity that affects the heart.” This definition not only includes a direct effect of the drug on the heart, but also an indirect effect due to enhancement of hemodynamic flow alterations or due to thrombotic events. Cardiotoxicity can develop in a subacute, acute, or chronic manner. The risk for such effects depends upon: cumulative dose, rate of drug administration, mediastinal radiation, advanced age, younger age, female gender, pre-existing heart disease and hypertension. Anthracyclines, such as doxorubicin (DOX), cause serious cardiac side-effects. Acute tachyarrhythmias and acute heart failure (HF) may occur after high doses, but these reactions are now rare due to changed dosage schemes (e.g. slower infusion) with the aim to prevent this. However, the sub-acute or chronic cardiac effects of anthracyclines remain a clinical problem. Clinically, anthracycline induced cardiotoxicity manifests itself as left ventricular failure, which develops insidiously over months to years after completion of the anthracycline based chemotherapy and may result in congestive HF. The mechanism of anthracyclin induced cardiotoxicity is not totally unraveled. It is likely that the decline in myocardial function is related to apoptosis of cardiac myocytes that occurs apparently at random in the myocardium. Anthracyclin induced formation of reactive oxygen species (ROS) in the presence of intracellular iron, impaired homeostasis of intracellular iron and calcium (that may facilitate the apoptosis induced by the ROS) have been put forward as mechanisms. Cardiac protection can be achieved by limitation of the cumulative dose. Further, addition of the antioxidant and iron chelator dexrazoxane to anthracycline therapy has shown to be effective in lowering the incidence of anthracycline induced cardiotoxicity.

Staphylococcal sepsis presenting as pulmonary embolism.

Deep vein thrombosis in children is rare and is often secondary to a predisposing condition. Staphylococcal sepsis following furunculosis and complicated by deep vein thrombosis and septic pulmonary emboli in a fourteen-yr-old boy is presented. He was managed successfully with antibiotics and anticoagulation.