Subcutaneous panniculitis-like T-cell lymphoma: fever and facial swelling with hemophagocytic syndrome.

We report a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) in a young man presenting with fever and facial swelling. He had pancytopenia and hemophagocytic syndrome (HPS) on evaluation. The histopathological examination of skin punch biopsy from the face and chest wall showed SPTCL. Given the associated HPS, he was started on steroid and multidrug chemotherapy following which he had symptomatic improvement.

Knowledge and Skills in Cardiopulmonary Resuscitation and Effect of Simulation Training on it among Healthcare Workers in a Tertiary Care Center in India.

Aim and background: High-quality cardiopulmonary resuscitation (CPR) is associated with improved patient outcomes, but healthcare workers (HCWs) may be frequently undertrained. This study aimed to assess baseline knowledge and skills among HCWs about basic and advanced life support and the effect of simulation-based training on it. Methods: It was a single-center prospective quasi-interventional study among resident doctors and nurses at a Tertiary Center in New Delhi, India. A questionnaire-based assessment was done to assess baseline knowledge. The participants then underwent simulation-based training followed by questionnaire-based knowledge assessment and skill assessment. A repeat questionnaire-based assessment was done 6 months post-training to assess knowledge retention. Results: A total of 82 HCWs (54 doctors and 28 nurses) were enrolled. The participants scored 22.28 ± 6.06 out of 35 (63.65%) in the pre-training knowledge assessment, with low scores in post-cardiac arrest care, advanced life support, and defibrillation. After the training, there was a significant rise in scores to 28.32 ± 4.08 out of 35 (80.9%) (p < 0.01). The retention of knowledge at 6 months was 68.87% (p < 0.01). The participants scored 92.61 ± 4.75% marks in skill assessment with lower scores in chest compressions and team leadership roles. There was a positive correlation (r = 0.35) between knowledge and skills scores (p < 0.01). Conclusion: There is a progressive decrease in baseline knowledge of HCWs with the further steps in the adult chain of survival. The simulation training program had a positive impact on the knowledge of HCWs. The training programs should focus on defibrillation, advanced life support, post-cardiac arrest care, and leadership roles. How to cite this article: Agarwal A, Baitha U, Ranjan P, Swarnkar NK, Singh GP, Baidya DK, et al. Knowledge and Skills in Cardiopulmonary Resuscitation and Effect of Simulation Training on it among Healthcare Workers in a Tertiary Care Center in India. Indian J Crit Care Med 2024;28(4):336-342.

Metagenomic insights into fungal community composition of the nasopharyngeal region of COVID-19 associated mucormycosis patients from India.

Coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM) was reported predominantly from India during the second wave of COVID-19  and has a high mortality rate. The present study aims to understand the fungal community composition of the nasopharyngeal region of CAM-infected individuals and compare it with severe COVID-19 patients and healthy controls. The fungal community composition was decoded by analyzing the sequence homology of the internal transcribed spacer-2-(ITS-2) region of metagenomic DNA extracted from the upper respiratory samples. The alpha-diversity indices were found to be significantly altered in CAM patients (p < 0.05). Interestingly, a higher abundance of Candida africana, Candida haemuloni, Starmerella floris, and Starmerella lactiscondensi was observed exclusively in CAM patients. The interindividual changes in mycobiome composition were well supported by beta-diversity analysis (p < 0.05). The current study provides insights into the dysbiosis of the nasal mycobiome during CAM infection. In conclusion, our study shows that severe COVID-19 and CAM are associated with alteration in mycobiome as compared to healthy controls. However, the sequential alteration in the fungal flora which ultimately leads to the development of CAM needs to be addressed by future studies.

Utility of an in-house real-time PCR in whole blood samples as a minimally invasive method for early and accurate diagnosis of invasive mould infections.

INTRODUCTION: Invasive mould infections (IMIs) are a leading cause of death in patients with compromised immune systems. Proven invasive mould infection requires detection of a fungus by histopathological analysis of a biopsied specimen, sterile culture, or fungal DNA amplification by PCR in tissue. However, the clinical performance of a PCR assay on blood samples taken from patients suspected of invasive mould disease has not been fully evaluated, particularly for the differential diagnosis of invasive aspergillosis (IA) and invasive Mucormycosis (IM). OBJECTIVES: To assess the diagnostic utility of our previously validated in-house real-time PCR in blood samples for diagnosis of invasive aspergillosis and mucormycosis in patients with suspected invasive mould infection. METHODS: All patients with suspected invasive mould infection were prospectively enrolled from May 2021 to July 2021. Conventional fungal diagnosis was performed using tissue and respiratory samples. In-house PCR was performed on blood samples and its diagnostic performance evaluated. RESULTS: A total of 158 cases of suspected invasive mould infection were enrolled in the study. The sensitivity and specificity of in-house PCR performed on blood samples was found to be 92.5% and 81.4% respectively for diagnosis of probable IA, and 65% and 84.62% respectively for diagnosis of proven and probable IM. It was also able to detect 3 out of 5 cases of possible IM where no other microbiological evidence of IM was obtained. CONCLUSIONS: This assay could be helpful in minimally invasive diagnosis of IMIs for patients in whom invasive sampling is not feasible, especially as a preliminary or screening test. It can help in early diagnosis, anticipating conventional laboratory confirmation by days or weeks. Possible correlation between fungal load and mortality can help in initiating aggressive treatment for patients with high initial fungal load.

Epidemiological, clinical, and laboratory characteristics of human granulocytic anaplasmosis in North India.

Human granulocytic anaplasmosis (HGA) is an emerging, rickettsial tick-borne disease caused by Anaplasma phagocytophilum. Sero-epidemiological data demonstrate that this pathogen has a worldwide distribution. The diagnosis of HGA requires a high index of clinical suspicion, even in endemic areas. In recent years, HGA has increasingly been reported from Asia and described in China, Japan, and Korea. We serologically and molecularly screened 467 patients with clinical suspicion of Anaplasmosis. The present study describes the epidemiology, clinical, and laboratory details of 6 confirmed and 43 probable cases of human granulocytic anaplasmosis. One of the HGA patients developed secondary invasive opportunistic Aspergillus fumigatus and Acinetobacter baumanii infection during the illness, which resulted in a fatal infection. The HGA patients without severe complications had excellent treatment responses to doxycycline. The emergence of this newly recognized tick-borne zoonotic HGA in North India is a significant concern for public health and is likely underdiagnosed, underreported, and untreated. Hence, it is also essential to establish a well-coordinated system for actively conducting tick surveillance, especially in the forested areas of the country.IMPORTANCEThe results of the present study show the clinical and laboratory evidence of autochthonous cases of Anaplasma phagocytophilum in North India. The results suggest the possibility of underdiagnosis of HGA in this geographical area. One of the HGA patients developed secondary invasive opportunistic Aspergillus fumigatus and Acinetobacter baumanii infection during the illness, which resulted in a fatal infection.

Effect of volume of instillate on the diagnostic utility of bronchoalveolar lavage galactomannan in patients with suspected chronic pulmonary aspergillosis-A pilot study.

BACKGROUND: Bronchoalveolar lavage (BAL) galactomannan (GM) is commonly used to diagnose Aspergillus-related lung diseases. However, unlike serum GM, which is measured in undiluted blood, BAL-GM is estimated using variable aliquots and cumulative volume of instillates during bronchoscopy. OBJECTIVE: Since different studies have reported varying diagnostic accuracy and cut-offs for BAL-GM in CPA, we hypothesized that the total volume of instillate and 'order/label' of aliquots significantly affects the BAL-GM values, which was evaluated as part of this study. PATIENTS & METHODS: We obtained 250 BAL samples from 50 patients (five from each) with suspected chronic pulmonary aspergillosis. BAL fluid was collected after instilling sequential volumes of 40 mL of normal saline each for the first four labels and a fifth label was prepared by mixing 1 mL from each of the previous labels. The GM level of each label was measured by PLATELIA™ ASPERGILLUS Ag enzyme immunoassay. This study measured the discordance, level of agreement, diagnostic characteristics (sensitivity, specificity and AUROC) and best cut-offs for BAL-GM in the different aliquots of lavage fluid. RESULTS: The study population, classified into CPA (28%) and non-CPA (72%) groups, based on ERS/ESCMID criteria (excluding BAL-GM) were not different with respect to clinico-radiological characteristics. The discordance of BAL-GM positivity (using a cut-off of >1) between the serial labels for the same patient ranged between 10% and 22%, while the discordance between classification using BAL-GM positivity (using a cut-off of ≥1) and clinic-radio-microbiological classification ranged between 18% and 30%. The level of agreement for serial labels was at best fair (<0.6 for all except one 'label'). The AUROC for the serial samples ranged between 0.595 and 0.702, with the '40 mL and the 'mix' samples performing the best. The best BAL-GM cut-off also showed significant variation between serial labels of varying dilutions (Range:1.01 - 4.26). INTERPRETATION: This study highlights the variation in BAL-GM measured and the 'positivity' between different 'labels' of aliquots of BAL, with the first aliquot and the mixed sample showing the best performances for diagnosis of CPA. Future studies should attempt to 'standardise' the instilled volume for BAL-GM estimation to standardise the diagnostic yield.

Evaluation of kit-based loop-mediated isothermal amplification (TB-LAMP) assay in the diagnosis of tubercular lymphadenitis.

Background: The rapid and accurate diagnosis of tubercular lymphadenitis remains a challenging task today. The World Health Organization (WHO) endorsed the LoopAMP MTBC kit (TB-LAMP) as a replacement for sputum smear microscopy in the diagnosis of pulmonary tuberculosis (PTB). However, no prospective diagnostic accuracy study of TB-LAMP for tubercular lymphadenitis in adults has been performed yet. The current study evaluated the diagnostic performance of TB-LAMP in tubercular lymphadenitis (LNTB). Methods: In a prospective observational study conducted at a tertiary care hospital in India, 90 subjects (age >18 years) suspected of LNTB were recruited consecutively and followed up for 6 months between January 2019 and December 2020. Samples were processed for microscopy, culture, GeneXpert, histopathology and TB-LAMP. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of TB-LAMP against the composite reference standard (CRS) and culture were determined. Results: TB-LAMP showed a sensitivity of 83.78 % (95 % CI, 73.76-90.47) and a specificity of 81.25 % (95 % CI, 56.99-93.41), respectively, against the CRS. The PPV and NPV were 95.38 % (95 % CI, 87.29-98.42) and 52.00 % (95 % CI, 33.50-69.97), respectively. TB-LAMP showed a sensitivity of 88.89 % (95 % CI, 71.94-96.15) and a specificity of 36.17 % (95 % CI, 23.97-50.46), respectively, against culture. The PPV and NPV were 44.44 % (95 % CI, 32-57.62) and 85 % (95 % CI, 63.96-94.76), respectively. Conclusion: TB-LAMP can be used instead of conventional microscopy for the diagnosis of TB in lymph node specimens at primary healthcare centres. It provides rapid and cost-effective diagnosis of LNTB in resource-limited settings due to good sensitivity and NPV.

Diagnosis and Management of Latent Tuberculosis Infection: Updates.

India has the largest problem of tuberculosis (TB) infection globally (estimated at about 35-40 crores cases), and around 18-36 lakh develop active tuberculosis annually. Latent TB is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens with no evidence of clinically manifested active TB. The progression of a latent infection to active tuberculosis increases several-fold in children < 5 years of age and in people with some or the other form of an immunocompromising condition. Therefore, to cater to this gigantic problem of tuberculosis, it is necessary to have awareness about latent tuberculosis infection (LTBI) amongst clinicians and to prioritise its diagnosis and treatment in high-risk groups. India plans to end TB well before the deadline set by the World Health organisation (WHO). However, this can only be achieved with effective strategies targeting LTBI. Multiple treatment regimens have been approved for LTBI treatment, and all have comparable efficacy. The selection of one regimen over the other depends on various factors, such as availability, risk of adverse events, age, and drug interactions. Recently, the WHO, as well as the Revised National TB Control Programme (RNTCP), have updated their guidelines on TB preventive treatment in 2020 and 2021, respectively. This review has been especially prepared to acknowledge the differences in approach to LTBI in developed and developing countries.

Malarial Antibodies and Endemicity: Does It Affect SARS-CoV-2 Severity and Outcomes?

Background India has a disproportionately lower rate of coronavirus disease 2019 (COVID-19) severe disease and lower death rates with respect to other parts of the world. It has been proposed that malaria-endemic countries such as India are relatively protected against severe COVID-19 disease and deaths. Methods This was a cross-sectional, analytical, observational study conducted from August 2020 to July 2021 at a tertiary care COVID-19-designated center in New Delhi, India. It aimed to study the association between antimalarial antibody levels and COVID-19 disease severity and outcomes. Results One hundred forty-six patients were included in the final analysis. The mean (standard deviation {SD}) age of the study population was 44.6 (17.2) years, and there were 85 (58.2%) males. Sixty-five patients had mild disease, 14 patients had moderate disease, and 67 patients had severe disease at the time of enrolment in the study. Forty-six patients expired during the hospital stay. For the antimalarial antibody, there was a statistically significant difference between mild and moderate (p=0.018), mild and severe (p=0.016), and mild and combined moderate and severe diseases (p=0.013). However, there was no difference between the patients who survived and those who did not. Conclusion Antimalarial antibody levels may not be associated with the outcomes of COVID-19 during hospital stay. However, this study has provided some insights into the relationship between the severity and outcomes of COVID-19 and the levels of antimalarial antibodies.

Functional and transcriptional heterogeneity within the massively expanding HLADR+CD38+ CD8 T cell population in acute febrile dengue patients.

IMPORTANCE: CD8 T cells play a crucial role in protecting against intracellular pathogens such as viruses by eliminating infected cells and releasing anti-viral cytokines such as interferon gamma (IFNγ). Consequently, there is significant interest in comprehensively characterizing CD8 T cell responses in acute dengue febrile patients. Previous studies, including our own, have demonstrated that a discrete population of CD8 T cells with HLADR+ CD38+ phenotype undergoes massive expansion during the acute febrile phase of natural dengue virus infection. Although about a third of these massively expanding HLADR+ CD38+ CD8 T cells were also CD69high when examined ex vivo, only a small fraction of them produced IFNγ upon in vitro peptide stimulation. Therefore, to better understand such functional diversity of CD8 T cells responding to dengue virus infection, it is important to know the cytokines/chemokines expressed by these peptide-stimulated HLADR+CD38+ CD8 T cells and the transcriptional profiles that distinguish the CD69+IFNγ+, CD69+IFNγ-, and CD69-IFNγ- subsets.

The Utility of Galactomannan and Polymerase Chain Reaction Assays in Bronchoalveolar Lavage for Diagnosis of Chronic Pulmonary Aspergillosis.

The diagnosis of chronic pulmonary aspergillosis (CPA) is established by combined clinic-radio-microbiological criteria. Out of the different microbiological criteria, a positive serology for Aspergillus-specific IgG levels is the cornerstone of diagnosis. Alternatively, other microbiological evidence are sometimes sought viz., positive Aspergillus antigen (broncho-alveolar lavage fluid, i.e., BALF galactomannan ≥ 1.0), histopathological demonstration of the fungi following lung biopsy or resection, demonstration of hyaline septate hyphae in direct microscopy resembling Aspergillus spp. or its growth on a respiratory specimen. However, the exact roles of BALF- GM and the newer BALF-PCR have not been confirmed by studies till date. This study enrolled 210 patients with suspected CPA. Of the participants, 88 patients met the criteria for CPA, whereas 122 patients had an alternative diagnosis. The sensitivity-specificity of AsperGenius® PCR and "in-house" PCR were 52.27(36.69-67.54) %-33.78 (23.19-45.72) % and 36.36 (22.41-52.23) %-39.19 (28.04-51.23) % respectively. The sensitivity/specificity of BALF (> 1.0) and serum galactomannan (> 1.0) were 46.55% (33.34-60.13)/64.08% (54.03-73.3) and 29.82% (22.05-37.6)/86.84% (81.1-92.59) respectively. The optimal cut-off values for BALF-Galactomannan and serum galactomannan in diagnosing CPA were found to be 0.69 (sensitivity: 64%; specificity: 53%) and 0.458 (sensitivity: 67%; specificity: 64%) respectively. This results of this study suggests that Aspergillus PCR from BAL may not be a good "rule-in" test for diagnosing CPA. While the performances of GM in BAL and serum may be better than PCR, it should be best used in conjunction with other clinical, radiological, and other microbiological characteristics.

Baroreflex sensitivity is impaired in survivors of mild COVID-19 at 3-6 months of clinical recovery; association with carotid artery stiffness.

The association between the stiffening of barosensitive regions of central arteries and the derangements in baroreflex functions remains unexplored in COVID-19 survivors. Fifty-seven survivors of mild COVID-19 (defined as presence of upper respiratory tract symptoms and/or fever without shortness of breath or hypoxia; SpO2 > 93%), with an age range of 22-66 years (27 females) participated at 3-6 months of recovering from the acute phase of RT-PCR positive COVID-19. Healthy volunteers whose baroreflex sensitivity (BRS) and arterial stiffness data were acquired prior to the onset of the pandemic constituted the control group. BRS was found to be significantly lower in the COVID survivor group for the systolic blood pressure-based sequences (BRSSBP ) [9.78 (7.16-17.74) ms/mmHg vs 16.5 (11.25-23.78) ms/mmHg; p = 0.0253]. The COVID survivor group showed significantly higher carotid ß stiffness index [7.16 (5.75-8.18) vs 5.64 (4.34-6.96); (p = 0.0004)], and pulse wave velocity ß (PWVß ) [5.67 (4.96-6.32) m/s vs 5.12 (4.37-5.41) m/s; p = 0.0002]. BRS quantified by both the sequence and spectral methods showed an inverse correlation with PWVß in the male survivors. Impairment of BRS in the male survivors of mild COVID-19 at 3-6 months of clinical recovery shows association with carotid artery stiffness.

Serological profile of patients suspected with non-scrub typhus rickettsioses.

BACKGROUND: Rickettsial pathogens are Gram-negative, obligate intracellular bacteria. They are transmitted by arthropods and are responsible for a wide variety of disease, from minor to life-threatening, which have a global effect on human health. Limited data are available on the prevalence of rickettsial diseases from India, and the disease epidemiology is not fully described. This study aimed to diagnose non-scrub typhus rickettsioses including spotted fever and typhus group of Rickettsia in clinically suspected patients by using standard serological tests and recognition of common epidemiological conditions and clinical manifestations. METHODS: During the study period, a total of 700 patients of all ages with acute febrile illness were enrolled. Patients were screened for rickettsial infection using IgM Enzyme-linked immunosorbent assay (ELISA) and Immunofluorescence assay (IFA) was performed to confirm the ELISA positive results. The relevant demographic, clinical, and laboratory details of patients were documented and analyzed. RESULTS: Of 700 samples tested, 141 (20.2%) were found to be positive for IgM antibodies against rickettsioses using ELISA and IFA. SFGR was positive in 15 (2.2%), TGR was positive in 112 (16%) and 14 (2%) samples were positive for both groups. 20 (14.2%) patients required admission to the intensive care unit (ICU), and 24 (17%) in-hospital deaths occurred. CONCLUSIONS: The prevalence of rickettsioses in India appears to be underestimated; therefore, increased awareness and improved diagnostic testing could facilitate early detection of cases, pathogen-targeted appropriate treatment, and improved outcomes for patients. Despite the fact that Rickettsiae can be isolated or detected using molecular techniques in clinical specimens, serology still remains the most commonly used diagnostic method for rickettsioses around the world. Our study helps bridge the gap of limited data on Rickettsia in north India and could be useful for future epidemiological investigation of rickettsial diseases and outbreaks.

Acute Cerebellar Ataxia: A Rare Association of Hepatitis a Infection.

Acute cerebellar ataxia (ACA) is a self-limited syndrome that is frequently post-infectious, most commonly following Varicella infection having an autoimmune mechanism. ACA is the commonest cause of childhood ataxia. We report a 14-year-old male who presented with acute onset wide-based gait and slurring of speech with dysdiadochokinesia, incoordination of voluntary movements, pendular knee jerk, and intentional tremors. He had worsening transaminitis and rising bilirubin during his hospital course and was subsequently found to be hepatitis A virus (HAV) immunoglobulin-M antibody positive. Thus, we report a case of ACA with HAV infection who developed jaundice after three weeks of onset of ataxia, a rarity that has not been reported so far in medical literature.

The Outbreak of SARS-CoV-2 in a Medical Ward and Its Containment: An Experience From a Tertiary Care Centre in North India.

Background Periodic outbreaks of SARS-CoV-2 in hospital settings amidst the recent pandemic are well known. However, the timely control of such outbreaks was key to preventing morbidity among vulnerable patients as well as reducing sickness absenteeism among healthcare workers. This is the first study of its kind in India. Methods An outbreak investigation was conducted between June 12 and July 18, 2020, at the All India Institute of Medical Sciences, New Delhi, India, during the first wave of COVID-19. Results A total of 27 individuals were infected during this time, including people visiting the hospital and healthcare workers. A thorough investigation led us to the epidemiological link between cases and allowed us to bring reforms to the existing hospital policy of screening and admission of COVID-19 patients and those suspected to have the infection. This experience helped us avoid future outbreaks during the second wave of COVID-19 in our hospital. Conclusion The SARS-CoV-2 virus is highly transmissible, especially in hospital settings due to the high burden of patients and close proximity between patients. Timely intervention is the key to effective control of hospital outbreaks, as it can avoid morbidity in patients and reduce sickness absenteeism among healthcare workers.

Utility of in-house and commercial PCR assay in diagnosis of Covid-19 associated mucormycoss in an emergency setting in a tertiary care center.

Introduction. Invasive mucormycosis (IM) is a potentially fatal infection caused by fungi of the order Mucorales. Histopathology, culture, and radiology are the mainstays of diagnosis, but they are not sufficiently sensitive, resulting in delayed diagnosis and intervention. Recent studies have shown that PCR-based techniques can be a promising way to diagnose IM.Hypothesis/Gap Statement. Early diagnosis of fungal infections using molecular diagnostic techniques can improve patient outcomes, especially in invasive mucormycosis.Aim. The aim of this study was to evaluate the utility of our in-house mould-specific real time PCR assay (qPCR) in comparison with the commercially available real time PCR (MucorGenius PCR), for the early diagnosis of mucormycosis in tissue samples from patients with suspicion of invasive mucormycosis (IM). This in-house assay can detect and distinguish three clinically relevant mould species, e.g. Aspergillus spp., Mucorales and Fusarium spp. in a single reaction with only one pair of primers, without the need for sequencing.Methodology. We enrolled 313 tissue samples from 193 patients with suspected IM in this prospective study. All cases were classified using EORTC/MSGERC guidelines. All samples were tested using traditional methods, in-house qPCR, and MucorGenius PCR.Results. Using direct microscopy as a gold standard, the overall sensitivity and specificity of in-house qPCR for detection of IM was 92.46% and 80% respectively, while that of the MucorGenius PCR was 66.67% and 90% respectively. However, co-infection of IM and IA adversely affected the performance of MucorGenius PCR in detection of IM.The in-house PCR detected Aspergillus spp. in 14 cases and Fusarium spp. in 4 cases which showed clinical and radiological features of fungal sinusitis. The in-house qPCR also performed better in detecting possible cases of IM. This aids early diagnosis and appropriate treatment to improve patient outcomes.Conclusion. Because the in-house PCR is not only sensitive and specific, but also entirely based on SYBR Green for detection of targets, it is less expensive than probe-based assays and can be used on a regular basis for the diagnosis of IM in resource-constrained settings. It can be used to distinguish between mucormycosis and fungal sinusitis caused by Aspergillus and Fusarium in high-risk patients, as well as to accurately detect Mucorales in fungal co-infection cases.

Escalate: Linezolid as an add on treatment in the intensive phase of tubercular meningitis. A randomized controlled pilot trial.

Most drugs used in the treatment of Tuberculous Meningitis have limited CNS penetration thereby limiting efficacy. CSF penetration of linezolid is 80-100%.The study was a prospective, randomized, open label with blinded outcome assessment pilot trial carried out in patients with TBM. Patients were randomized in a 1:1 ratio into two treatment groups either to receive standard ATT alone or add on oral 600 mg BD Linezolid for 4 weeks along with standard four drug ATT [HRZE/S]. Primary outcome was safety and mortality at the end of one and three months measured by intention to treat analysis. 29 patients were recruited and 27 completed three months of follow up. There was no significant difference in terms of mortality with Odds ratio (95% CI) of 2 (0.161-24.87; p = 1) at one month and 0.385 (0.058-2.538; p = 0.39) at three months. There was a significant improvement in GCS in Linezolid group at one month and mRS within the Linezolid group at one and three months. No major safety concerns were observed. The sample size is underpowered to draw any definitive conclusions but improvement in mRS and GCS as well as mortality change make a case for a large sample size trial.