Steady states and kinetic modelling of the acid-catalysed ethanolysis of glucose, cellulose, and corn cob to ethyl levulinate.

Ethyl levulinate is a promising advanced biofuel and platform chemical that can be derived from lignocellulosic biomass by ethanolysis processes. It can be blended with both diesel and gasoline and, thus, used in conventional engines and infrastructure. Previously, it has been shown that alkyl levulinate/alcohol/alkyl ether mixtures exhibit significantly enhanced fuel properties relative to any of the individual fuel components, particularly when blended with conventional hydrocarbon liquid fuels. Consequently, this study specifically quantifies the three primary components of the alcoholysis reaction mixture: ethyl levulinate, diethyl ether, and ethanol. The steady state and kinetic phase fractions of ethyl levulinate and diethyl ether produced from glucose, cellulose, and corn cob with 0.5-2 mass% sulphuric acid in ethanol are determined for 5, 10, and 20 mass% of feedstock at 150 °C. Knowledge of the steady state equilibrium mixture fraction is specifically targeted due to its importance in assessing commercial-scale production and in modelling analysis as: (i) it defines the maximum yield possible at a given condition, and (ii) it is equitable to the minimum free energy state. Maximum steady state yields (mass%) of ethyl levulinate of (46.6 ± 3.7), (50.2 ± 5.4), and (27.0 ± 1.9)% are determined for glucose, cellulose, and corn cob, respectively. The conversion of glucose and cellulose to ethyl levulinate in the presence of ethanol and sulphuric acid is shown to be a catalytic process, where the ethyl levulinate yield is not dependent on the acid concentration. For corn-cob biomass, in a new and contrasting finding, the ethyl levulinate yield is shown to strongly depend on the acid concentration. This effect is also observed in the fractions of diethyl ether formed, providing strong evidence that the hydrogen cation is not being replenished in the ethanolysis process and the overall reaction with corncob is not wholly catalytic. Thus, for the acid catalysed alcoholysis of lignocellulosic biomass, acid concentration must be scaled with feedstock concentration. The critical corn cob-to-acid ratio that maximises ethyl levulinate yields while minimizing the formation of undesired co-products (diethyl ether) is in the range 10-20 : 1 at 150 °C. A detailed, hierarchical, mass-conserved chemical kinetic model capable of accurately predicting the relative abundance of the three primary components of the ethanolysis reaction: ethyl levulinate, diethyl ether, and ethanol, from the biochemical composition of the feedstock, is elucidated and validated.

Case Report: Chorea as a Rare Manifestation of Secondary Adrenal Insufficiency.

The word "chorea" comes from the Latin word "choreus," which means dancing movement. Chorea is defined as a hyperkinetic movement disorder characterized by uncontrolled, unintended, jerky, brief, irregular, random movements involving the limbs or facial muscles. Here, we discuss the case of a 48-year-old male with hypothyroidism for two years, which is well-controlled with medication. He presented with behavioral disturbances for the past seven months and choreiform movements affecting all four limbs, his tongue, and his face for the past six months. Investigations revealed hyponatremia and low serum osmolality. An MRI of the brain showed the empty sella sign. Further investigations revealed low levels of adrenocorticotropic hormone (ACTH), prolactin, and testosterone. Considering the diagnosis of chorea with euvolemic hyponatremia due to secondary adrenal insufficiency, the patient was started on tetrabenazine, trihexyphenidyl, oral hydrocortisone, and gradual correction of sodium level. The patient's condition improved during the hospital stay, and he continues to do well in routine follow-ups.

Neurolymphomatosis as an Initial Presentation of Non Hodgkins Lymphoma: A Case Report.

Neurolymphomatosis (NL) is a rare clinical disease where neoplastic cells invade the cranial nerves, roots, plexus, or other peripheral nerves in patients with hematologic malignancy mainly Non-Hodgkins Lymphoma(NHL). Primary NL occurs as the first manifestation of a hematologic malignancy. We report a 68-year male who presented to us with low backache and burning paraesthesia in the back of both lower limbs followed by a left foot drop. The clinical and electrophysiological examination was suggestive of bilateral lumbosacral radiculopathy involving L2-S1 roots. Plain MRI of the lumbosacral spine was normal. F18FDG PET CT Scan revealed increased uptake in both L5 and left L3 roots. Contrast-enhanced MRI of the lumbosacral spine showed marked fusiform thickening and enhancement of both L5 and left L3 roots CT-guided Biopsy from left L5 root, lymph node, and bone marrow was suggestive of large B cell lymphoma-germinal center cell type. The diagnosis was neurolymphomatosis secondary to NHL.

Acute Subdural Hematoma: A Rare Manifestation of Cerebral Venous Sinus Thrombosis.

Cerebral venous sinus thrombosis (CVST) usually presents with headaches, seizures, and signs and symptoms of raised intracranial pressure (ICP). Risk factors for CVST commonly include hypercoagulable states such as pregnancy and the peripartum period, dehydration, vitamin B12 deficiency, hyper-homocysteinemia, coagulation factor deficiency, antiphospholipid antibody disease, oral contraceptive pill intake, etc. CVST with venous hemorrhagic infarction is commonly reported, but only a few cases have been reported in the literature of CVST presenting as SDH. Here, we present a case of a 28-year-old female who presented with an acute onset of severe headache, vomiting, and bilateral papilledema on fundus examination. She had a prior history of oral contraceptive pill intake. An MRI brain venogram suggested CVST involving the superior sagittal sinus, right transverse, and a few cortical vein thromboses with subdural hematoma (SDH) in the frontal-parieto-temporo-occipital region on the right side. The patient was treated with anticoagulants and antiepileptics and had significant improvement in symptoms with the resolving SDH on subsequent scans.

Psychiatric Symptoms and Fatigue in COVID-19 Survivors.

INTRODUCTION: Psychiatric symptoms and fatigue are common after the coronavirus disease 2019 (COVID-19) illness. The cause of these symptoms is direct neuronal injury and indirect injury with immune-mediated inflammation. In addition, social factors also affect mental health. OBJECTIVE: We aim to compare psychiatric symptoms and fatigue between COVID-19 survivors and healthy controls. MATERIAL AND METHODS: We prospectively evaluated 100 COVID-19 survivors for anxiety, depression, positive affect, and behavior control using the Mental Health Inventory (MHI). Fatigue is assessed using the Modified Fatigue Impact Scale (MFIS) score. We compared them with 100 healthy controls. RESULTS: There was a significant statistical difference between the MHI score and individual components of MHI. Overall, MHI scores in cases and controls were 79.41 and 93.31, respectively, with a P value of less than 0.0001. Computed scores for anxiety, depression, behavior control, and positive affect of COVID-19 survivors showed statistically significant differences as compared to healthy controls. There was a weak association between hospital stay duration and poor MHI scores. Fatigue was significantly worse in COVID-19 survivors, with a mean score of 6.93 in cases and 5.35 in controls, with a P value of 0.0001. This was a cross-sectional study evaluating psychiatric symptom scores, but not establishing the diagnosis. It is suggested that appropriate treatment and counseling for these symptoms should be done. CONCLUSIONS: Psychiatric symptoms and fatigue were significantly more common in COVID-19 patients after recovery from acute illness. It is a major contributing cause of morbidity other than organic complications of COVID-19 and requires attention in management.

Predictors of disease severity in COVID-19 associated mucormycosis: impact of HbA1C levels, time lag to mucormycosis onset, and radiologic patterns of paranasal sinuses and spaces involvement.

BACKGROUND: Identifying early predictors of severe Covid-19 associated mucormycosis (CAM) can help improve management and treatment outcomes. OBJECTIVES: Primary: To identify clinical and radiological predictors of disease severity in CAM. Secondary: To describe patterns of central nervous system (CNS) involvement in CAM. METHODS: A total of 71 patients with CAM were included in the study. Based on the anatomical extent of involvement on MRI, patients were divided into three groups: Sinus (paranasal sinuses), Orbit (orbital spread), and CNS (CNS spread). Clinical parameters and radiological patterns of involvement of sinuses and extra sinus spaces were studied between the three groups. Patterns of CNS involvement were also described. RESULTS: A shorter time lag between COVID-19 infection and CAM, as well as high HbA1C levels, were found to be associated with severe disease. Involvement of the sphenoid, ethmoid and frontal sinuses, T1 hyperintense signal in the sphenoid, as well as bony involvement of the sphenoid sinus, were significantly associated with severe disease. Extra-sinus spread into pre/retroantral space, pterygopalatine fossa, and masticator spaces were also significantly associated with a severe disease course. The most common pattern of CNS spread was cavernous sinus involvement, followed by pachymeningeal spread and cranial nerve involvement. CONCLUSION: Early identification of the above-described predictors in patients presenting with CAM can help detect those at risk for developing severe disease. A longer duration of amphotericin, combined with a more aggressive surgical approach in selected cases, may lead to better long-term outcomes.

Satellite Epidemic of Covid-19 Associated Mucormycosis in India: A Multi-Site Observational Study.

BACKGROUND: Sudden upsurge in cases of COVID-19 Associated Mucormycosis (CAM) following the second wave of the COVID-19 pandemic was recorded in India. This study describes the clinical characteristics, management and outcomes of CAM cases, and factors associated with mortality. METHODS: Microbiologically confirmed CAM cases were enrolled from April 2021 to September 2021 from ten diverse geographical locations in India. Data were collected using a structured questionnaire and entered into a web portal designed specifically for this investigation. Bivariate analyses and logistic regression were conducted using R version 4.0.2. RESULTS: A total of 336 CAM patients were enrolled; the majority were male (n = 232, 69.1%), literate (n = 261, 77.7%), and employed (n = 224, 66.7%). The commonest presenting symptoms in our cohort of patients were oro-facial and ophthalmological in nature. The median (Interquartile Range; IQR) interval between COVID diagnosis and admission due to mucormycosis was 31 (18, 47) days, whereas the median duration of symptoms of CAM before hospitalization was 10 (5, 20) days. All CAM cases received antifungal treatment, and debridement (either surgical or endoscopic or both) was carried out in the majority of them (326, 97.02%). Twenty-three (6.9%) of the enrolled CAM cases expired. The odds of death in CAM patients increased with an increase in HbA1c level (aOR: 1.34, 95%CI: 1.05, 1.72) following adjustment for age, gender, education and employment status. CONCLUSION: A longer vigil of around 4-6 weeks post-COVID-19 diagnosis is suggested for earlier diagnosis of CAM. Better glycemic control may avert mortality in admitted CAM cases.

Higher proinflammatory responses possibly contributing to suppressed cytotoxicity in patients with COVID-19 associated mucormycosis.

INTRODUCTION: COVID-19 Associated Mucormycosis (CAM), an opportunistic fungal infection, surged during the second wave of SARS Cov-2 pandemic. Since immune responses play an important role in controlling this infection in immunocompetent hosts, it is required to understand immune perturbations associated with this condition for devising immunotherapeutic strategies for its control. We conducted a study to determine different immune parameters altered in CAM cases as compared to COVID-19 patients without CAM. METHODOLOGY: Cytokine levels in serum samples of CAM cases (n = 29) and COVID-19 patients without CAM (n = 20) were determined using luminex assay. Flow cytometric assays were carried out in 20 CAM cases and 10 controls for determination of frequency of NK cells, DCs, phagocytes, T cells and their functionalities. The cytokine levels were analyzed for their association with each other as well as with T cell functionality. The immune parameters were also analyzed with respect to the known risk factors such as diabetes mellitus and steroid treatment. RESULTS: Significant reduction in frequencies of total and CD56 + CD16 + NK cells (cytotoxic subset) was noted in CAM cases. Degranulation responses indicative of cytotoxicity of T cell were significantly hampered in CAM cases as compared to the controls. Conversely, phagocytic functions showed no difference in CAM cases versus their controls except for migratory potential which was found to be enhanced in CAM cases. Levels of proinflammatory cytokines such as IFN-γ, IL-2, TNF-α, IL-17, IL-1ß, IL-18 and MCP-1 were significantly elevated in cases as compared to the control with IFN-γ and IL-18 levels correlating negatively with CD4 T cell cytotoxicity. Steroid administration was associated with higher frequency of CD56 + CD16- NK cells (cytokine producing subset) and higher MCP-1 levels. Whereas diabetic participants had higher phagocytic and chemotactic potential and had higher levels of IL-6, IL-17 and MCP-1. CONCLUSION: CAM cases differed from the controls in terms of higher titers of proinflammatory cytokines, reduced frequency of total and cytotoxic CD56 + CD16 + NK cell. They also had reduced T cell cytotoxicity correlating inversely with IFN-γ and IL-18 levels, possibly indicating induction of negative feedback mechanisms while diabetes mellitus or steroid administration did not affect the responses negatively.

Neuromyelitis Optica Presenting as Non-Communicating Hydrocephalus: A Case Report.

Neuromyelitis Optica (NMO) is a demyelinating disease predominantly involving optic nerves, spinal cord and peri-ventricular regions which are rich in Aquaporin-4 receptors. Aquaporin-4 (AQP4) antibodies are implicated in the pathogenesis of NMO. Association of hydrocephalus ( communicating and non communicating) with NMO is very rare. We report a case of 32 years old female patient who presented with 2 months history of progressive headache, visual obscurations and gait imbalance . Clinical examination revealed bilateral papilloedema with preserved visual acuity. She had truncal and gait ataxia. Rest of the examination of nervous system was normal. MRI brain showed non- communicating hydrocephalus and T2 and FLAIR hyperintensities in periventricular and periaqueductal regions. AQP4 antibodies were positive in serum and negative in cerebrospinal fluid(CSF). Ventriculo - peritoneal shunt was placed and she was treated with steroids and azathioprine. Her headache and visual symptoms improved. However, after 8 months she presented with acute optic neuritis of right eye which was treated with intravenous methylprednisolone and plasmapharaesis.

A case control investigation of COVID-19 associated mucormycosis in India.

BACKGROUND: Increased occurrence of mucormycosis during the second wave of COVID-19 pandemic in early 2021 in India prompted us to undertake a multi-site case-control investigation. The objectives were to examine the monthly trend of COVID-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with development of CAM. METHODS: Eleven study sites were involved across India; archived records since 1st January 2021 till 30th September 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls. RESULTS: CAM-case admissions reached their peak in May 2021 like a satellite epidemic after a month of in-patient admission peak recorded due to COVID-19. The odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95% CI 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95% CI 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95% CI 1.02, 1.11) and use of methylprednisolone (aOR: 2.71, 95% CI 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95% CI 0.08, 0.41). Genomic sequencing of archived respiratory samples revealed similar occurrences of Delta and Delta derivates of SARS-CoV-2 infection in both cases and controls. CONCLUSIONS: Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients have the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to such prevention efforts.

Novel transthyretin gene mutation in familial amyloid neuropathy in India: Case.

Familial amyloid polyneuropathy (PN), also known as amyloid transthyretin (TTR)-PN is an autosomal dominant adult-onset fatal disease, if not treated. It occurs due to mutations in (TTR) gene which leads to a faulty TTR protein which folds up to form amyloid and gets deposited mainly on nerves and causes length-dependent PN and autonomic dysfunction. We report a case of a 45-year-old female who presented with symptoms of painful peripheral neuropathy for 5 months, a history of deafness for 5 years, and cardiac pacemaker implantation 2 years ago for complete heart block. She denied any symptoms of autonomic dysfunction. Her brother with similar symptoms died of cardiac arrest at the age of 50 years. Clinical examination was suggestive of symmetrical sensorimotor PN. The nerve conduction study was suggestive of axonal sensorimotor PN. Abdominal fat biopsy was negative for amyloid. Sural nerve biopsy was suggestive of amyloid neuropathy. Genetic analysis showed c. 165G > T mutation encoding amino acid p. Lys55Asn on exon-4 of TTR gene. This mutation has not been reported from India.

Résumé La polyneuropathie amyloïde familiale (NP), également connue sous le nom de transthyrétine amyloïde (TTR) -PN, est une maladie mortelle autosomique dominante de l'adulte, si elle n'est pas traitée. Il se produit en raison de mutations du gène (TTR) qui conduisent à une protéine TTR défectueuse qui se replie pour former de l'amyloïde et se dépose principalement sur les nerfs et provoque une PN dépendante de la longueur et un dysfonctionnement autonome. Nous rapportons le cas d'une femme de 45 ans qui présentait des symptômes de neuropathie périphérique douloureuse depuis 5 mois, des antécédents de surdité depuis 5 ans et l'implantation d'un stimulateur cardiaque il y a 2 ans pour un bloc cardiaque complet. Elle a nié tout symptôme de dysfonctionnement autonome. Son frère présentant des symptômes similaires est décédé d'un arrêt cardiaque à l'âge de 50 ans. L'examen clinique évoquait une NP sensorimotrice symétrique. L'étude de la conduction nerveuse était évocatrice d'une NP sensorimotrice axonale. La biopsie de la graisse abdominale était négative pour l'amyloïde. La biopsie du nerf sural était évocatrice d'une neuropathie amyloïde. L'analyse génétique a montré c. Mutation 165G > T codant pour l'acide aminé p. Lys55Asn sur l'exon-4 du gène TTR. Cette mutation n'a pas été signalée en Inde. Mots clés: Neuropathie amyloïde familiale, tests génétiques, biopsie nerveuse, amylose à transthyrétine.

Acute Onset Flaccid Paraplegia with Monocular Diminution of Vision in a Case of Chikungunya Infection.

Chikungunya is a common tropical viral infection in India. The majority of patients have limited systemic manifestations. Neurological manifestations of chikungunya may be due to direct viral infection or immune mediated. We present a case of a 45-year-old male who presented with acute onset paraplegia with diminution of vision in the right eye. A detailed evaluation revealed a diagnosis of chikungunya myeloradiculitis with viral keratitis. The patient was treated with steroids followed by intravenous immunoglobulin and had a good recovery.

Rhino-Orbito-Cerebral Mycosis and COVID-19: From Bad to Worse?

Background: There has been an increase an alarming rise in invasive mycoses during COVID-19 pandemic, especially during the second wave. Aims: Compare the incidence of invasive mycoses in the last three years and study the risk factors, manifestations and outcomes of mycoses in the COVID era. Methodology: Multicentric study was conducted across 21 centres in a state of western India over 12-months. The clinico-radiological, laboratory and microbiological features, treatment and outcomes of patients were studied. We also analysed yearly incidence of rhino-orbito-cerebral mycosis. Results: There was more than five-times rise in the incidence of invasive mycoses compared to previous two-years. Of the 122 patients analysed, mucor, aspergillus and dual infection were seen in 86.9%, 4.1%, and 7.4% respectively. Fifty-nine percent had simultaneous mycosis and COVID-19 while rest had sequential infection. Common presenting features were headache (91%), facial pain (78.7%), diplopia (66.4%) and vison loss (56.6%). Rhino-orbito-sinusitis was present in 96.7%, meningitis in 6.6%, intracranial mass lesions in 15.6% and strokes in 14.8%. A total of 91.8% patients were diabetic, while 90.2% were treated with steroids during COVID-19 treatment. Mortality was 34.4%. Conclusion: Invasive fungal infections having high mortality and morbidity have increased burden on already overburdened healthcare system. Past illnesses, COVID-19 itself and its treatment and environmental factors seem responsible for the rise of fungal infection. Awareness and preventive strategies are the need of hours and larger studies are needed for better understanding of this deadly disease.

Atypical Multiple Sclerosis with Antibody to MOG.

CASE PRESENTATION: We report a case of a young female who had magnetic resonance imaging (MRI) brain lesions typical of multiple sclerosis (MS) with cerebrospinal fluid (CSF) oligoclonal bands (OCBs) and definite multiple sclerosis based on revised McDonald criteria; however, she also had atypical features of mild pleocytosis, brainstem and cerebellar peduncle involvement apart from opticospinal (OS) involvement. She also turned out to be positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibody; hence, she was diagnosed with atypical multiple sclerosis. This case highlights when to suspect atypical MS and its management approach. DISCUSSION: Typical MS cases are largely anti-MOG-negative. In a study of 50 Japanese cases, with anti-aquaporin 4 (AQP4)-immunoglobulin (IgG)-negative OSMS, just 2 were MOG-IgG-positive, but they had some features atypical for MS, such as bilateral optic neuritis, longitudinally extensive transverse myelitis, or moderate pleocytosis. In another study, antibodies to MOG were found in about 5% (5/104) of preselected adult patients with MS. Patients with MS with antibodies to MOG showed typical MS lesions on brain MRI with concomitant severe brainstem and spinal cord involvement and had a severe disease course with high relapse rates. CONCLUSION: In conclusion, any patient showing typical MS lesions on brain MRI with OCB present in CSF but has atypical features like mild pleocytosis with brainstem, cerebellar, or OS involvement should also be tested for autoantibodies to MOG, and if positive, then he/she would require aggressive treatment approach in the form of plasma exchange, if resistant to pulse steroid therapy, followed by either rituximab or natalizumab rather than trying other disease modifying therapies (DMTs).

Reply to the Letter to Editor Regarding "An Unusual Case of Critical Illness Polyneuromyopathy".

Critical illness myopathy (CIM), critical illness polyneuropathy (CIP), and critical illness polyneuromyopathy (CIPNM) are the group of disorders that are commonly presented as neuromuscular weakness in intensive care unit (ICU) settings. They are responsible for prolonged ICU stay and failure to wean off from mechanical ventilation.1 We report one such case of young female who was admitted with undiagnosed type I diabetes mellitus with diabetic ketoacidosis with severe hypokalemia with sepsis developed acute-onset quadriplegia and diaphragmatic palsy within 72 hours of ICU admission. Detailed investigation led to the diagnosis of critical illness polyneuromyopathy. In view of high morbidity, mortality, and poor prognosis, a guided approach to diagnoses and treatment in earliest possible duration might give better improvement and outcome of the illness. Despite all the odds, our patient showed good clinical improvement and finally got discharged. HOW TO CITE THIS ARTICLE: Mahashabde M, Chaudhary GA, Kanchi G, Rohatgi S, Rao P, Patil R, et al. Reply to the Letter to Editor Regarding "An Unusual Case of Critical Illness Polyneuromyopathy". Indian J Crit Care Med 2020;24(7):604-605.

An Unusual Case of Critical Illness Polyneuromyopathy.

Critical illness myopathy (CIM), critical illness polyneuropathy (CIP), and critical illness polyneuromyopathy (CIPNM) are the group of disorders that are commonly presented as neuromuscular weakness in intensive care unit (ICU) settings. They are responsible for prolonged ICU stay and failure to wean off from mechanical ventilation. We report a case of young female who was admitted with undiagnosed type I diabetes mellitus with diabetic ketoacidosis, severe hypokalemia, sepsis developed acute onset quadriplegia, and diaphragmatic palsy within 72 hours of ICU admission. On detailed investigation, CIPNM was diagnosed. In view of high morbidity, mortality, and poor prognosis, a guided approach to diagnose and treat in earliest possible duration might give better improvement and outcome of the illness. Despite all the odds, our patient showed good clinical improvement and finally got discharged. HOW TO CITE THIS ARTICLE: Mahashabde M, Chaudhary G, Kanchi G, Rohatgi S, Rao P, Patil R, et al. An Unusual Case of Critical Illness Polyneuromyopathy. Indian J Crit Care Med 2020;24(2):133-135.