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 Second- vs First-wave COVID-19: More of the Same or a Lot Worse? A Comparison of Mortality between the Two Waves in Patients Admitted to Intensive Care Units in Nine Hospitals in Western Maharashtra.

BACKGROUND: India, along with the rest of the world, faced the challenging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The second wave in India lagged behind that in the Western world, due to different timing of seasons. There is scarce data about the differences between the two waves, for intensive care unit (ICU) patients. We present the data of 3,498 patients from 9 ICUs of western Maharashtra. MATERIALS AND METHODS: We collected prospective data of hospitalized, RT-PCR confirmed, coronavirus-2019 (COVID-19) patients, from nine tertiary centers, after institutional ethics committee (IEC) approval. Then, we segregated and analyzed the data of patients admitted to the ICU, for comorbidities, high-resolution computed tomography (HRCT) score, ventilatory support, etc. The primary outcomes were ICU and hospital mortality. We also performed multivariable analysis for predictors of ICU mortality. RESULTS: Overall, there were 3,498 ICU patients. In the first wave, 1,921 patients needed ICU admission, while in the second wave, 1,577 patients. Patients in the second wave had significantly higher ICU (26.1 vs 13.4%, p <0.001) and hospital mortality (29.9 vs 18.2%, p <0.001) and need for ventilatory support of any type. More patients received steroids during the second wave. On multivariable regression, male gender, ICU admission during the second wave, increasing HRCT score, and need for intubation and mechanical ventilation were significant predictors of ICU mortality. CONCLUSION: ICU patients admitted during the two waves were of the similar age, but there were more females, and more patients had comorbidities during the second wave. The ICU and hospital mortality were significantly higher during the second wave. HOW TO CITE THIS ARTICLE: Zirpe KG, Dixit S, Kulkarni AP, Pandit RA, Ranganathan P, Prasad S, et al. The Second- vs First-wave COVID-19: More of the Same or a Lot Worse? A Comparison of Mortality between the Two Waves in Patients Admitted to Intensive Care Units in Nine Hospitals in Western Maharashtra. Indian J Crit Care Med 2021; 25(12):1343-1348.

Increased growth temperature and vitamin B12 supplementation reduces the lag time for rapid pathogen identification in BHI agar and blood cultures.

Background: The rapid diagnostics of pathogens is essential to prescribe appropriate and early antibiotic therapy. The current methods for pathogen detection require the bacteria to grow in a culture medium, which is time-consuming. This increases the mortality rate and the global burden of antimicrobial resistance. Culture-free detection methods are still under development and are not used in the clinical routine. Therefore decreasing the culture time for accurate detection of infection and resistance is vital for diagnosis. Methods: In this study, we wanted to investigate easy-to-implement factors (in a minimal laboratory set-up), including inoculum size, incubation temperature, and additional supplementation ( e.g., vitamin B12 and trace metals), that can significantly reduce the lag time (t lag). These factors were arranged in simple two-level factorial designs using Gram-positive ( Escherichia coli and Pseudomonas aeruginosa) and Gram-negative ( Staphylococcus aureus and Bacillus subtilis) bacteria, including clinical isolates with known antimicrobial resistance profiles. Blood samples spiked with a clinical isolate of E. coli CCUG17620 were also tested to see the effect of elevated incubation temperature on bacterial growth in blood cultures. Results: We observed that increased incubation temperature (42°C) along with vitamin B12 supplementation significantly reduced the t lag (10 - 115 minutes or 4% - 49%) in pure clinical isolates and blood samples spiked with E. coli CCUG17620. In the case of the blood sample, PCR results also detected bacterial DNA after only 3h of incubation and at three times the CFU/mL. Conclusions: Enrichment of bacterial culture media with growth supplements such as vitamin B12 and increased incubation temperature can be a cheap and rapid method for the early detection of pathogens. This is a proof-of-concept study restricted to a few bacterial strains and growth conditions. In the future, the effect of other growth conditions and difficult-to-culture bacteria should be explored to shorten the lag phase.

Synchronous Primary Adenocarcinoma of Distal Common Bile Duct and Gall bladder.

Synchronous primary cancer of the gall bladder and distal common bile duct is rare. There are only few case reports and case series available of these synchronous cancers. Management of this tumor is individualized in these case reports and series based upon the presentation. We present a case of a patient who had multifocal adenocarcinoma involving distal common bile duct and gall bladder. Keywords: Distal common bile duct cancer; gall bladder cancer; synchronous primary.

Real-time ultrasound-guided spinal anaesthesia vs pre- procedural ultrasound-guided spinal anaesthesia in obese patients.

BACKGROUND AND AIMS: Spinal anaesthesia is conventionally performed using a landmark-guided midline approach. These surface landmarks may be absent, indistinct or distorted in the presence of obesity, previous spinal surgeries, deformities, or degenerative changes associated with ageing. In the present study, we compared the efficacy of real-time ultrasound (RUS)-guided paramedian approach, and pre-procedure ultrasound (PUS) landmark-guided paramedian approach in obese patients. METHODS: Eighty patients with body mass index (BMI) >30 kg/m2 were included in the study. The participants were randomly assigned to two intervention groups, i.e., RUS and PUS approach. The primary end point was to attain a successful lumbar puncture. Variables like the number of attempts, the number of passes, the time taken for identifying landmark(s), and time for a successful lumbar puncture(s) were secondary end points and were recorded in both the groups. RESULTS: The median number of attempts were 4 (IQR 2-4) and 2 (IQR 1-2), respectively, in the PUS and RUS group (P-value < 0.001). The median number of passes, the median time for identifying space, and the time for successful lumbar puncture was statistically significantly less in the RUS group, than the PUS group. CONCLUSION: The time taken for the identification of the space, the number of attempts, number of passes, and the time taken for successful lumbar puncture was more in the PUS group as compared to the RUS group.

Ultrasound of adnexal masses.

Current advancements in imaging technology, especially three-dimensional/four-dimensional ultrasound and contrast-enhanced imaging, have increased the diagnostic yield of adnexal masses. The benefit of ultrasound is the characterization of an adnexal mass, suggesting the probable etiology of the mass. Masses may be divided as solid, cystic, or complex. It is predominantly the solid and complex masses that need a thorough evaluation. The role of color-flow imaging is now gaining importance and criteria for distinguishing between benign and malignant masses are often possible. Availability of a scoring system enables the differentiation of small adnexal masses. Several benign lesions may present as complex masses but can be distinguished and diagnosed on sonography. The availability of 3D ultrasound has been of great use to understand spatial relations and vascular morphology. Sonography allows a more detailed assessment of morphologic features of an adnexal mass. With a benign-appearing adnexal mass on sonography, the need for any further diagnostic tests is often obviated.

Factors determining outcomes in adult patient undergoing mechanical ventilation: A "real-world" retrospective study in an Indian Intensive Care Unit.

BACKGROUND: Characteristics of patients admitted to intensive care units with respiratory failure (RF) and undergoing mechanical ventilation (MV) have been described for particular indications and diseases, but there are few studies in the general Intensive Care Unit (ICU) population and even lesser from developing countries. OBJECTIVE: This study aims to study clinical characteristics, outcomes, and factors affecting outcomes in adult patients with RF on MV admitted to ICU. METHODS: A retrospective study of medical records of all patients admitted to ICU between January 1, 2015, and March 31, 2016. Patients receiving MV for more than 6 h were included in the study. Patients younger than 12 years were excluded. Data were recorded of all patients receiving MV during this period regarding demographics, indications for MV, type and characteristics of ventilation, concomitant complications and treatment, and outcomes. Data were recorded at the initiation of MV and daily all throughout the course of MV. The main outcome measure was all-cause mortality at the end of ICU stay. RESULTS: Of the 500 patients admitted to the ICU during the period of the study, a total of 122 patients received MV (and were included in study) for mean (standard deviation [SD]) duration of 4 (3.4) days. The mean (SD) stay in ICU and hospital was 4.49 (3.52) and 6.4 (3.6), respectively. Overall mortality for the unselected general ICU patients on MV was 67.21% while that for ARDS patients was 76.1%. The main factors independently associated with increased mortality were (i) pre-MV factors: age, Apache II scores, heart failure (odds ratio [OR], 1.42; 95% confidence interval [CI], 0.54-3.73; P < 0.001); (ii) patient management factors: positive end-expiratory pressure (OR, 2.69; 95% CI, 0.84-8.61; P < 0.001); (iii) Factors occurring over the course of MV: PaO2/FiO2 ratio < 100 (OR, 1.66; 95% CI, 0.67-4.11; P < 0.001) and development of renal failure (OR, 2.33; 95% CI, 2.05-2.42; P < 0.001) and hepatic failure (OR, 2.07; 95% CI, 1.91-2.24; P < 0.001) after initiation of MV. CONCLUSIONS: Outcomes of patients undergoing MV are dependent on various factors (including patient demographics, nature of associated morbidity, characteristics of the MV received, and conditions developing over course of MV) and these factors may be present before or develop after initiation of MV.

Prospective Validation of a Decision Tree Model for Prediction of Severity in Acute Pancreatitis.

BACKGROUND: Early identification of severe acute pancreatitis is important for early stratification, goal directed fluid therapy, rationalizing level of care to improve outcome. Various clinical, laboratory and imaging scoring system has been used to identify severe acute pancreatitis with variable results. Recently a decision tree model was proposed using serum creatinine, serum lactate dehydrogenase and oxygenation index to predict severe acute pancreatitis. This system is easy and usable at our centre. Hence, we conducted the study to validate the decision tree model prospectively. METHODS: Patients admitted with a diagnosis of acute pancreatitis were included in the study. Decision tree model was used to identify patients at high and low risk for severe acute pancreatitis. Sensitivity and specificity were calculated for prediction of the decision tree model. RESULTS: Fifty-three patients were included in the study. Fourty-one (77.4 %) patients with mild acute pancreatitis, five (9.4 %) patients had moderately severe pancreatitis and seven (13.2 %) patients had severe acute pancreatitis. Sensitivity and specificity of decision tree model to predict severity of pancreatitis was 97.83%(95 % CI - 88.47% to 99.94%) and 71.43 % % (95 % CI - 29.04% to 96.33%) respectively with positive and negative predictable value of 95.74 % % (95 % CI - 87.45% to 98.64%) and 83.33 % % (95 % CI - 40.49% to 97.35%) respectively. CONCLUSIONS: Decision tree model with serum creatinine, lactate dehydrogenase, and oxygenation index is an easy and useful tool to predict patients at high risk of developing severe acute pancreatitis.

Appropriateness of Indications of Upper Gastrointestinal Endoscopy and its Association With Positive Finding.

INTRODUCTION: Upper Gastrointestinal Endoscopy is a frequently advised investigation for upper abdominal symptoms. Studies have questioned the appropriateness of indications for upper gastrointestinal endoscopy and have shown that inappropriate indications range from 5% to 49%. The unnecessary upper gastrointestinal endoscopy expose patients to the risk. The number of upper gastrointestinal endoscopy is rising in our region and we assume so is the number of unnecessary upper gastrointestinal endoscopy. With an aim to find out the appropriateness of the indications of upper gastrointestinal endoscopy and compare its association with positive findings, we conducted a cross-sectional descriptive study. METHODS: All patients undergoing diagnostic upper gastrointestinal endoscopy during study period were included in the study. Appropriateness of indications for upper gastrointestinal endoscopy was defined as per American Society for Gastrointestinal Endoscopy criteria as "appropriate" and "inappropriate". Upper gastrointestinal endoscopy findings were classified as "significant" and "insignificant" based on endoscopy findings. The extent of this association between appropriateness of indications and upper gastrointestinal endoscopy findings was expressed as the odds ratio of finding a relevant diagnosis in patients with an ''appropriate'' indication compared with those with an 'inappropriate'' indication. RESULTS: Seventy-nine patients were included in the study. Fifty- two (65.8%) of the indications were considered appropriate as per American Society for Gastrointestinal Endoscopy guidelines. Thirty-three (63.5%) of the appropriate indications has clinically significant finding as compared to seven (25.9%) of inappropriate indication with an odds ratio of 4.962 (95% CI:1.773 - 13.890, P=0.002) which is statistically significant. CONCLUSIONS: Appropriate indications have significantly higher rates of clinically significant findings. Use of guidelines may decrease the number of unnecessary procedures.

Alcohol dehydrogenase: a potential new marker for diagnosis of intestinal ischemia using rat as a model.

AIM: Intestinal ischemia (Ii) is an abdominal emergency due to blockade of the superior mesenteric artery resulting in 60-100% mortality if diagnosed late. Changes in several biochemical parameters such as D (-)-lactate, Creatinine kinase isoenzymes and lactate dehydrogenase suggested for early diagnosis, lack specificity and sensitivity. Therefore a biochemical parameter with greater sensitivity needs to be identified. METHODS: Wistar male rats were randomly assigned into two groups; control sham operated (n = 24) and ischemic test (n = 24) group. Superior mesenteric arterial occlusion was performed in the ischemic test group for 1 h. Alcohol dehydrogenase (ADH) was estimated in blood from portal vein, right ventricle of heart, dorsal aorta (DA) and inferior vena cava (IVC). The Serum glutamic acid pyruvate transaminase (SGPT) was also estimated in blood from portal vein and right ventricle of heart. RESULTS: A significant increase (P<0.001) in the levels of ADH in both portal blood as well as heart blood of the test group (232.72+/-99.45 EU and 250.85+/-95.14 EU, respectively) as compared to the control group (46.39+/-21.69 EU and 65.38+/-30.55 EU, respectively) were observed. Similarly, increased levels of ADH were observed in blood samples withdrawn from DA and IVC in test animals (319.52+/-80.14 EU and 363.90+/-120.68 EU, respectively) as compared to the control group (67.68+/-63.22 EU and 72.50+/-58.45 EU, respectively). However, in test animals there was significant increase in SGPT in portal blood (P = 0.054) without much increase in heart blood. CONCLUSION: Significant increase in the levels of ADH in portal and heart blood within 1 h of SMA occlusion without increase in SGPT in heart blood, suggests that the origin of ADH is from ischemic intestine and not from liver. Similarly, raised ADH levels were found in DA and IVC as well. IVC blood does represent peripheral blood sample. A raised level of ADH in test animals confirms it to be a potential marker in the early diagnosis of Ii.

Artificial neural network application in the diagnosis of disease conditions with liver ultrasound images.

The preliminary study presented within this paper shows a comparative study of various texture features extracted from liver ultrasonic images by employing Multilayer Perceptron (MLP), a type of artificial neural network, to study the presence of disease conditions. An ultrasound (US) image shows echo-texture patterns, which defines the organ characteristics. Ultrasound images of liver disease conditions such as "fatty liver," "cirrhosis," and "hepatomegaly" produce distinctive echo patterns. However, various ultrasound imaging artifacts and speckle noise make these echo-texture patterns difficult to identify and often hard to distinguish visually. Here, based on the extracted features from the ultrasonic images, we employed an artificial neural network for the diagnosis of disease conditions in liver and finding of the best classifier that distinguishes between abnormal and normal conditions of the liver. Comparison of the overall performance of all the feature classifiers concluded that "mixed feature set" is the best feature set. It showed an excellent rate of accuracy for the training data set. The gray level run length matrix (GLRLM) feature shows better results when the network was tested against unknown data.

Role of ultrasound in evaluation of peripheral nerves.

Ultrasonography (USG) is an excellent cost-effective modality in imaging of peripheral nerves. With the newer high-frequency probes with different footprints which allow high-resolution imaging at relatively superficial location, USG can detect and evaluate traumatic, inflammatory, infective, neoplastic, and compressive pathologies of the peripheral nerves. This article describes the technique for evaluation of nerves by USG as well as the USG appearances of normal and diseased peripheral nerves.

Management of Severe Pancreaticoduodenal Injuries.

Severe pancreaticoduodenal injuries are rare and no surgeon and institute get enough number of cases to acquire expertise. Hence, the management of such injuries remains controversial. We report a case of 28 years male who sustained a severe pancreaticoduodenal injury and was managed with emergency pancreaticoduodenectomy with immediate reconstruction. Various approaches have been described in literature with variable outcome. Damage control strategy seems to be most useful approach and major resection should be a part of debridement whenever required. Immediate reconstruction can be carried out safely if patients remain hemodynamically and metabolically stable.

Role of biochemical investigation in prediction of biliary etiology in acute pancreatitis.

INTRODUCTION: Acute pancreatitis is common clinical presentation. Gall stone disease and alcohol consumption are most common etiologies. Detection of biliary etiology is important in order to provide definite management in form of cholecystectomy to prevent further attacks. Sensitivity for abdominal ultrasound to detect cholelithiasis is decreased to 67-87% in presence of acute pancreatitis. Difference in biochemical investigations of acute biliary and non-biliary pancreatitis has been proposed to increase the suspicion of biliary etiology. METHODS: Sixty patients admitted with diagnosis of acute pancreatitis from March 2012 to December 2012 were included in the study. The relation between etiology with age, sex, admission serum amylase and liver function test were evaluated. RESULTS: Out of 60 patients 38 (63.33%) and 22 (36.66%) had biliary and non-biliary etiology respectively. Biliary pancreatitis was more common in females (25 vs. 3). Distribution of severity was comparable between both groups. Biliary pancreatitis group had significantly higher amylase level (3466.42 vs. 1987.5, p 0.003) whereas values of liver function test were higher in biliary pancreatitis though not statistically significant. CONCLUSIONS: A simple, rapid and accurate prediction of biliary etiology of acute pancreatitis can be provided by changes in biochemical parameters.

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.