Real-world five-year outcomes of FlexyRap®cobalt-chromium rapamycin-eluting stents with biodegradable polymer in patients with de-novo coronary artery disease

BACKGROUND The use of biodegradable polymer drug-eluting stents(BP-DES)has been proven to minimize restenosis and stent thrombosis.The current post-marketing monitoring was observed at the 5-year clinical outcomes of individuals who had been treated with FlexyRap®DES in the real world.AIM To assess the safety and effectiveness of FlexyRap®DES at the 5-year follow-up in real-world settings.METHODS Findings from a retrospective,multi-center,observational,post-market clinical follow-up study of patients treated with FlexyRap®DES for de novo coronary artery disease(CAD)were reported.During the 12-mo follow-up,the primary endpoint was target lesion failure,which was defined as the composite of cardiovascular death, target vessel myocardial infarction(TV-MI), and clinically driven target lesion revascularization.RESULTS The data of 500 patients received with FlexyRap®DES was obtained at the completion of the surveillance timeline of 5-year.After the implantation of FlexyRap®DES,the device success rate was 100%.Adverse events that led to major bleeding,permanent disability,or death were not experienced in the patients.The major adverse cardiac event rate at 12-mo,3-year,and 5-year follow-up was 1(0.2%),0(0%),and 1(0.2%)respectively with 0(0%)cardiovascular death,2(0.4%)TV-MI,and 0(0%)TLR compositely.Furthermore,late stent thrombosis was found in 2(0.4%)patients at the follow-up of 12-mo,very late stent thrombosis was observed in 2 patients(0.4%)at 3-year follow-up.CONCLUSION FlexyRap®DES was proved to be safe and efficacious in real-world patients with de novo CAD,indicating a lowered rate of cardiac events and stent thrombosis at 5-year follow-up.

Gastrointestinal manifestations of Henoch-Schonlein purpura: A report of two cases

Henoch-Schonlein purpura(HSP) is a small vessel vasculitis mediated by type Ⅲ hypersensitivity with deposition of Ig A immune complex in the walls of vessels. It is a multi-system disorder characterizedby palpable purpura, arthritis, glomerulonephritis and gastrointestinal manifestations and commonly occurs in children and young adults. The patients with gastrointestinal involvement usually present with colicky abdominal pain, vomiting and melena. The imaging findings include multifocal bowel thickening with mucosal hyperenhancement, presence of skip areas, mesenteric vascular engorgement, with involvement of unusual sites like stomach, duodenum and rectum. These imaging findings in a child or young adult with appropriate clinical findings could suggest HSP.

Laparoscopic liver resection:Wedge resections to living donor hepatectomy, are we heading in the right direction?

Despite inception over 15 years ago and over 3000 completed procedures, laparoscopic liver resection has remained mainly in the domain of selected centers and enthusiasts. Requirement of extensive open liver resection(OLR) experience, in-depth understanding of anatomy and considerable laparoscopic technical expertise may have delayed wide application. However healthy scepticism of its actual benefits and presence of a potential publication bias; concern about its safety and technical learning curve, are probably equally responsible. Given that a large proportion of our work, at least in transplantation is still OLR, we have attempted to provide an entirely unbiased, mature opinion of its pros and cons in the current invited review. We have dividedthis review into two sections as we believe they merit separate attention on technical and ethical grounds. The first part deals with laparoscopic liver resection(LLR) in patients who present with benign or malignant liver pathology, wherein we have discussed its overall outcomes; its feasibility based on type of pathology and type of resection and included a small section on application of LLR in special scenarios like cirrhosis. The second part deals with the laparoscopic living donor hepatectomy(LDH) experience to date, including its potential impact on transplantation in general. Donor safety, graft outcomes after LDH and criterion to select ideal donors for LLR are discussed. Within each section we have provided practical points to improve safety in LLR and attempted to reach reasonable recommendations on the utilization of LLR for units that wish to develop such a service.

Novel en-bloc resection of locally advanced hilar cholangiocarcinoma: the Rex recess approach

Loco-regional recurrence after potentially curative resection remains a problem in hilar cholangiocarcinoma. Hilar dissection risks local spillage of tumor cells leading to suboptimal disease free survival. We have developed a new technique of radical resection for hilar cholangiocarcinoma based on the distinctive anatomy of the Rex recess of the liver, which has been assessed in two patients with locally advanced hilar cholangiocarcinoma. This technique included a right hepatectomy with en-bloc resection of the hepatoduodenal ligament and portal venous reconstruction to the left portal vein at the Rex recess. Both patients had R0 resection and have been disease-free for 26 and 38 months, respectively.

Matching donor to recipient in liver transplantation: Relevance in clinical practice

Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor,graft and recipient factors.Within the cohort of patients waiting for a transplant,better matching of the donor organ to the recipient will improve transplant outcomes and benefit the overall waiting list by minimizing graft failure and need for re-transplantation.A PubMed search was conducted to identify published literature investigating the effects of donor factors such as age,gender,ethnicity,viral serology;graft factors such as size and quality,recipient factors such as age,size,gender and transplant factors such as major or minor blood group incompatibility and immunological factors.We also report technical and therapeutic modifications that can be used to manage donor-recipient mismatch identified from literature and the authors’clinical experience.Multiple donor and recipient factors impact graft survival after liver transplantation.Appropriate matching based on donor-organ-recipient variables,modification of surgical technique and innovative peri-transplant strategies can increase the donor pool by utilizing grafts from marginal donors that are traditionally turned down.

Adenosine deaminase isoenzymes estimation - as a diagnostic tool for tuberculous pleural effusions

Objective:To assess the efficacy of ADA isoenzyme estimation over that of total ADA level in pleural fluid and serum as a more efficient diagnostic indicator in tuberculous pleural effusions in high prevalence country like India.Methods:The efficacy was analysed in total thirty four patients of pleural effusions.Total ADA was estimated by Guitsi and Galanti Calorimetric method and ADA isoenzymes with and without EHNA[Erythro-9-（2- hydroxy-3-nonyl） adenine]a potent ADA1 inhibitor using the same method.Results:The results demonstrated a statistically significant values of ADA2 in serum（P【0.001）,pleural fluid（P = 0.000） and significant value for the ratio of pleural fluid ADA2/serum ADA2（P【0.001） and pleural fluid ADA/ADA(2（P【0. 005）.The sensitivity and specificity values of pleural fluid ADA|2 is 81.8%and 91.6%（cut off value 60 IU/L for Tuberculous effusions）,serum ADA2 95.4%and 66%（cut off value 70 IU/L for tuberculous effusions）. ADA2 is an isoenzyme,which is significantly raised in tuberculous pleural effusions both in the serum and pleural fluid.Conclusion:Estimation of ADA isoenzymes is redundant as a diagnostic aid over total ADA estimation in view of the limited improvements both in specificity and sensitivity patterns and also in term of cost-benefit ratio.

Cope's sign and complete heart block secondary to acute cholecystitis: A case report

Rationale: Cope's sign is reflex bradycardia seen in the patient presenting with symptoms of acute cholecystitis. This bradycardia may be due to vagally mediated cardio-biliary reflex. Many of these reflexes due to acute cholecystitis have similar clinical features (some electrocardiographic changes like bradycardia, complete heart block, and asystole) mimicking that of acute coronary syndrome. Patient's concern: A 60-year old male presented with symptoms of acute cholecystitis and referred to the emergency department with complete heart block and abdominal pain with hypotension requiring an emergency temporary pacemaker. Diagnosis: Cope's sign and complete heart block. Intervention: Emergency temporary cardiac pacemaker insertion. Outcomes: The patient was discharged after three days with regular follow-up and advice for laparoscopic cholecystectomy. Lessons: Complete heart block or any symptomatic bradycardia associated with abdominal pain should be under consideration of cholecystitis that may be associated with either presence or absence of gall stones due to cardio biliary reflex.

Serum Procalcitonin and Neutrophil Toxic Granules Guided Management of Post-Operative <i>K. pneumoniae</i>Septic-Shock in Laminectomy—A Case Report

Introduction: We still rely on clinical diagnosis for initiating empirical antibiotic therapy and await blood culture for confirmation of infection, species identification and drug sensitivity. Differential blood cell count (WBC and neutrophils) and recording of toxic granules in the neutrophils are established methods for indirect diagnosis of infection though they are not used in the diagnosis of sepsis per se. Serum Procalcitonin is considered as a good biomarker in the management of sepsis. Materials and Methods: Whole blood and serum were used for laboratory analysis. We have combined the detection of toxic granules in the peripheral blood smear and serum PCT levels for diagnosis and monitoring the recovery of a patient with septic shock. A 63 year old laminectomy patient was transferred 2 days after the surgery to our hospital with several co-morbidities and complications. He was in septic shock and was put on Continuous Renal Replacement Therapy, with ionotropic support and IV fluids via nasogastric feeding and administration of Activated Protein C. Blood culture and daily measurements of serum Procalcitonin, differential blood cells count, and observation of toxic granules in neutrophils were done. Results: The blood culture showed infection due to K. pneumoniae resistant to carbapenems. WBC and Neutrophil counts were quite variable and showed incoherent response to treatment. Serum PCT was 24.57 ng/mL on the next day of admission and it peaked at 30.2 ng/mL on day 3. Its level started decreasing from the 4th day. Toxic granules disappeared when serum PCT levels reached < 1 ng/mL. The patient responded well to treatment and he was discharged on the 16th day upon request. Conclusion: This case is presented as an example of managing sepsis with a combination of a conventional hematology marker and a modern biomarker. Resource poor hospitals with inadequate microbiology services, may evaluate and use these two biomarkers not only for the total management of sepsis but also to reduce the cost of critical care.

Hemolysins of <i>Staphylococcus aureus</i>—An Update on Their Biology, Role in Pathogenesis and as Targets for Anti-Virulence Therapy

Staphylococcus aureus is a dangerous gram positive bacterial pathogen which, not only evades the host’s immune system but also can destroy the leucocytes especially neutrophils. It has an embodiment of virulence factors most of which are secreted. Staphylococcus aureus secretes a number of toxins which cause tissue damage and facilitate spreading and nutrients uptake. Among the toxins, hemolysins α, β, γ, δ and Panton Valentine Leukocidin (PVL) are unique that they drill pores in the membrane, leading to the efflux of vital molecules and metabolites. Hemolysins also help in the scavenging of iron, although many of them also have leucolytic properties. α-hemolysin, also known as α-toxin, is the most prominent cytotoxin which damages a wide range of host cells including epithelial cells, endothelial cells, erythrocytes, monocytes, keratinocytes and it damages cell membrane and induces apoptosis. β-Hemolysin significantly affects human immune cell function. It has Mg2+ dependent sphingomyelinase activity and degrades sphingomyelin of plasma membrane into phosphorylcholine and ceramides. The bi-component leukocidins, which include γ-hemolysin and PVL, attack human phagocytic cells and greatly contribute to immune evasion. Delta toxin is a low molecular weight exotoxin with a broad cytolytic activity. Virulence determinants, quorum sensing and biofilm synthesis provide some attractive targets for design and development of a new group of antimicrobial compounds. This review provides an update on the structure, biological functions of hemolysins and their role in quorum sensing/biofilm synthesis (if any) and as effective therapeutic targets for anti-virulence drug development. We have tried to bring together information available on various aspects of hemolysins and highlighted their distribution among all species of Staphylococcus and other bacteria. We have updated the status of development of candidate drugs targeting the hemolysins for anti-virulence therapy as it offers an additional strategy to reduce the severity of infection and which would, through quorum quenching, delay the development biofilms leading to drug resistance.

Gram-negative bacteria causing infective endocarditis: Rare cardiac complication after liver transplantation

Bacterial endocarditis is a rare complication amongst solid organ transplant recipients and is often linked to bacteremia. Majority of these recipients do not have underlying valvular heart disease or congenital valvular abnormalities. Staphylococoocusaureus and Enterococcus species are the most commonly isolated organisms. There are very few reports of gram-negative bacteria causing endocarditis in liver transplant recipients. We report a 51-yearold male, a liver transplant recipient, who developed bacterial endocarditis of the mitral valve due to extended spectrum of betalactamase producing strain of Escherichia coli and was managed successfully with antibiotics.

Tuberculosis treatment-new approach to an old problem

Chronic mycobacterium infections are major causes of disease burden of 20%in a tropical country like India. The inflammatory cascade following these bacterial infections often leads to tissue damage and perpetuates necrosis, fibrosis and the disease process.Pulmonary tuberculosis,multi-drug resistant tuberculosis not only affects individuals but society at large.Current remedial measures using various technology platforms singularly did not produce effective and appreciable reduction in global disease burden.On the contrary,the conventional chemotherapeutic chemical moieties have demonstrated variable pharmacogenomic expression,increased drug resistance,non compliance of strict prolonged drug regimens with debilitating side effects and contraindications. Furthermore,secreted inflammatory cytokines results in chronic infection,immune deviation,and immunopathology in the lungs.Hence,identification of immune escape mechanisms leading to chronic mycobacterial infections is crucial for development of new treatments.The review would dwell into the basic pathogenic mechanism and the newer approaches that may need to be considered for developing novel therapeutic strategies.

Heterogeneity in <i>femA</i>in the Indian Isolates of <i>Staphylococcus aureus</i>Limits Its Usefulness as a Species Specific Marker

Increase in prevalence of MRSA worldwide and hence the need for rapid detection, have led to use of molecular methods for confirmation of the species and also MRSA. Species specific markers like fem or nuc along with the methicillin-resistance determinant, mecA, have been used by several investigators worldwide for the identification of MRSA. In the current study, we have screened 54 microbiologically confirmed (MRSA, MSSA and CoNS) isolates for the presence of mecA, 16S rRNA, femA and nuc markers. While mecAPCR and 16S rRNAPCR results were consistent with other studies, femA and nuc showed dramatic variation in detection rate (sensitivity) of S. aureus 29.6% and 53.7% respectively. Evidences are presented to demonstrate the absence of femA. Our attempt to amplify the complete femA gene using sequences flanking femA further confirmed these results and also indicated that variations exist even in the genomic sequences around femA. Our data reveals the need for exercising care while using primers designed on sequences of constitutive genes like femA and nuc for PCR based identification of S. aureus species. Though geographic variations in the genome of S. aureus have previously been reported from around the world, we present here evidence for the first time from India for absence of femA and also for probable variations in the sequences around the femA gene in clinical isolates of S. aureus.

Concomitant Aortoplasty with Septal Myectomy for Supravalvar Aortic Stenosis in an Adult

Survival of patients with severe congenital aortic stenosis beyond third decade is uncommon. This report describes a 31 year old patient who underwent successful aortoplasty and in addition septal myectomy for complete relief of left ventricular outflow obstruction.

Arteriovenous Malformation (AVM) Treated with Robotic Radiosurgery: Impact of Beam Reduction in 12 Gy Normal Brain Volume and It’s Clinical Implication

Purpose: Dosimetric study to evaluate impact of “beam” reduction in AVM radiosurgery on normal brain dose parameters and it’s clinical implications. Materials and Methods: Five small volume AVMs (nidus volume 0.31 - 1.94 cc) planned for single fraction SRS with robotic radiosurgery system. Planning scans done with CT scan brain, CT & MR angiography, then nidus volume and organ at risk (OARs) were contoured. Planning was done with multiplan planning system. Plan evaluated as per Flickenger model parameters of 12 Gy nomal brain vol & marginal dose. 7.5 mm and 10 mm cons used, optimization done with seqential algorithm. 20 Gy was prescribed to isodose with appropriate nidus coverage (>98%). Total beams of five plans were 85 - 250, monitor unit 17,259 - 24,602 MU. 12 Gy normal brain volume is 0.9 - 7.6 cc. Then beam reduction is done by reducing beams with minimum MU in steps of 50, 100, 150, 200, 250 MU and after beam reduction, re-optimization done. Prescription isodose was changed to keep the nidus coverage > 98%. Impacts of beam reduction on 12 Gy normal brain vol and conformity/homogeniety index were analyzed. Results: Optimal plans of five patients with 20 Gy prescribed to 88% - 90% isodose, nidus coverage more than 98%. In dosimetric parameters, mean CI was 1.36 - 1.51, nCI 1.41 - 1.51, HI 1.1 - 1.4 and mean 12 Gy normal brain volume 0.17, 1.44, 5.3, 5.5 and 7.6cc respectively. After beam reduction of less than 50 MU contribution (in case#1), prescibing at suitable isodose (85%) beam reduces to 79 and 12 Gy volume marginally increases to 26.4 cc. Beam reduction of less than 100 MU reduces to 53 - 92 beamlets. Reduction of beams with less than 150 MU contribution did not significantly change the 12Gy normal brain volume. However, reduction of beamlets with more than 200 MU, 250 MU, 300 MU, 450 MU and 550 MU significantly affects the 12 Gy normal brain volume. Prescription-isodose modified from 83% to 50% to have >98% coverage. CI and HI increased from 1.36 - 1.51 to 2.51 - 2.63 and 1.1 - 1.4 to 1.52 - 1.54 respectively. There was exponential increase in 12 Gy volume with reduction of beams with higher proportion in larger nidus. Conclusions: In robotic radiosurgery system, beam reduction even after re-optimization impairs the conformity index and increase 12 Gy normal brain volume, hence long-term toxicity. Optimal beam numbers are required for optimal plan generation.

Mini versus ultra-mini percutaneous nephrolithotomy in a paediatric population

Objective:To evaluate whether there would be a difference in outcome when the smaller ultra-mini 12 Fr sheath was used instead of the mini 16 Fr sheath for percutaneous nephrolithotomy(PCNL)in paediatric patients for stones less than 25 mm.Methods:This was a prospective cohort study of patients who underwent PCNL in our hospital in a 2-year period from July 2016 to June 2018 by a single surgeon.PCNL was performed in a prone position and tract was dilated to the respective size using single step dilatation.Laser was used to fragment the stone.Stone-free outcome was defined as absence of stone fragment at 3 months on kidney,ureter,and bladder X-ray.Results:There were 40 patients in each group.Mean stone size was comparable between the two groups(14.5 mm vs.15.0 mm).The procedure was completed faster in the 16 Fr group compared to 12 Fr group(24.5 min vs.34.6 min).Stone clearance was highly successful in both groups(97.5%vs.95.0%).There was no difference in complications between the two groups.The decrease in hemoglobin was minimal in both groups(0.2 g/dL vs.0.3 g/dL).Conclusion:We found that the success rates were similar in both mini PCNL and the smaller ultra-mini PCNL groups.No significant difference in bleeding was noted in our pilot study,however,operative time was longer in the ultra-mini group as compared to the mini sheath group.

Clino-Pathological Features of Urinary Tract Infection in Rural India

The study was aimed to understand the clino-pathological characteristics of urinary tract infection along with the techniques used in diagnosis and treatment of the presenting infection. The study takes into consideration the various risk factors such as age, sex, and diabetes mellitus which can precipitate a urinary tract infection. The study was conducted at the Global Baroda Hospital, Vadodara and Narhari Hospital, Vadodara in the duration from January to March 2012, under the supervision of Dr. Hiten Kareliya. A questionnaire was prepared in accordance to evaluate risk factors of urinary tract infection. The patients under study were chosen according to specific inclusion criteria. The uropathogens were isolated with the help of biochemical testing. E. coli (38%) was found to be the most prevalent organism followed by Klebsiella and Candida albicans (both 10%), Pseudomonas aeruginosa (9%), Staphylococcus (7%).

A Simple Method for Direct Detection and Discrimination of <i>A. baumannii</i>in Tracheal Aspirates without Culture Isolation

Currently, available phenotyping and commercial methods report A. baumannii only as Acinetobacter calcoaceticus-baumannii complex (ACB) and do not identify individual members of the complex. This is a single blind study aimed to evaluate certain commonly used species-specific genetic markers namely, Intergenic Transcribed Spacer region in 16S rRNA of A. baumannii (Ab-ITS) and gyrB, for identification of ACB members. These molecular targets were first validated on clinical isolates (n = 200) and subsequently on uncultured tracheal aspirates (n = 172). Among the clinical isolates, 183/200 (91.5%) were positive for Ab-ITS. The clinical isolates 17 (17/200) which are failed to amplify in Ab-ITS PCR were subsequently diagnosed by gyrB PCR as A. calcoaceticus (n = 2), A. pitti (n = 6) and A. nosocomialis (n = 9) but not A. baumannii. Among the tracheal aspirates, 62 samples were reported as sterile in Advanced Expert System of VITEK-2, among the remaining 110 samples, 68.1% (75/110) samples contained Ab-ITS target. Twenty-five of the sterile samples (25/62) were found to contain Ab-ITS target sequence. Since, our sample processing method enabled identification of all the species of ACB complex by PCR even in uncultured tracheal aspirates, adaptation of our protocol would enable same day (6 - 8 h) reporting and help the clinician make evidence based therapeutic decision quickly.

Role of plasmapheresis in early allograft dysfunction following deceased donor liver transplantation

The role of plasmapheresis in liver failure and hepatic encephalopathy is undefined and its use as a strategy to salvage patients with severe allograft dysfunction after liver transplantation remains investigational. We present a case of early allograft dysfunction following deceased donor liver transplantation(DDLT) where plasmapheresis was effective as a bridge to recovery and possibly avoiding a retransplantation. A 16 years old boy, known to have decompensated Wilson's disease underwent DDLT at our Public Sector Hospital. He received a healthy liver from a brain-dead donor, whose liver was considered too large for the boy. The graft was reduced in situ to a left lobe graft. Surgery was uneventful and the recipient was well for the initial 96 h. On Doppler and further computed tomography scan, a partial portal vein thrombus was noted. He was reexplored and a Fogarty endothombecteomy was performed. Following the second surgery, he developed severe allograft dysfunction with a peak bilirubin of 40 mg/d L. He underwent imaging to rule out technical causes for the dysfunction, followed by a liver biopsy, which revealed acute cellular rejection. Multiple cycles of plasmapheresis were initiated. Over the next two weeks, the graft demonstrated a gradual recovery. He was discharged on the 30 th postoperative day, with a serum bilirubin of 5.5 mg/d L. He remains well on follow-up, with the liver function tests improving further. Our report demonstrates the beneficial effect of plasmapheresis, which appears to be an effective treatment option for early allograft dysfunction following liver transplantation and may obviate the need for retransplantation.

Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C

AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85-105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.

Cytokine Storm of COVID-19 and Its Impact on Patients with and without Chronic Liver Disease

The coronavirus pandemic has resulted in increased rates of hepatic decompensation,morbidity and mortality in patients suffering from existing liver disease,and deranged liver biochemistries in those without liver disease.In patients with cirrhosis with coronavirus disease 2019(COVID-19),new onset organ failures manifesting as acute-onchronic liver failure have also been reported.The severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)also directly binds to enterocytes and cholangiocytes via the angiotensin converting enzyme receptor 2,although the lung remains the portal of entry.Superadded with the COVID-19 related bystander hepatitis,a systemic inflammatory response is noted due to unregulated macrophage activation syndrome and cytokine storm.However,the exact definition and diagnostic criteria of the‘cytokine storm’in COVID-19 are yet unclear.In addition,inflammatory markers like C-reactive protein,ferritin,D-dimer and procalcitonin are frequently elevated.This in turn leads to disease progression,activation of the coagulation cascade,vascular microthrombi and immune-mediated injury in different organ systems.Deranged liver chemistries are also noted due to the cytokine storm,and synergistic hypoxic or ischemic liver injury,drug-induced liver injury,and use of hepatotoxic antiviral agents all contribute to deranged liver chemistry.Control of an unregulated cytokine storm at an early stage may avert disease morbidity and mortality.Several immunomodulator drugs and repurposed immunosuppressive agents have been used in COVID-19 with varying degrees of success.