A Case of Refractory Hypoxemic Respiratory Failure due to Antineutrophil Cytoplasmic Antibodies-associated Diffuse Alveolar Hemorrhage Rescued by Extracorporeal Membrane Oxygenation.

Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening disease. Mortality is very high in those patients who require mechanical ventilation. Traditionally, active bleeding has been considered a contraindication for extracorporeal membrane oxygenation (ECMO) support. There is limited evidence for ECMO in DAH as rescue therapy. Herein, we describe a case of antineutrophil cytoplasmic antibodies-associated DAH with intractable hypoxemic respiratory failure. An appropriate ventilator strategy failed to improve her hypoxemia leading to imminent risk to her life. The patient was rescued with veno-venous ECMO targeting lower than usual range of anticoagulation. ECMO proved to be lifesaving in our patient who was initiated on prompt immunosuppressive therapy and plasmapheresis along with continuous veno-venous hemodiafiltration and hemodynamic support. We feel that ECMO could be considered as adjunctive therapy in severe hypoxemic respiratory failure associated with DAH after careful consideration of the risk of bleeding and a restrictive anticoagulation strategy. How to cite this article: Goel MK, Chauhan M, Kumar A, Wadwa P, Maitra G, Talegaonkkar M, et al. A Case of Refractory Hypoxemic Respiratory Failure due to Antineutrophil Cytoplasmic Antibodies-associated Diffuse Alveolar Hemorrhage Rescued by Extracorporeal Membrane Oxygenation. Indian J Crit Care Med 2020;24(9):879-881.

Invasive pulmonary mycosis due to Chaetomium globosum with false-positive galactomannan test: a case report and literature review.

In this case, the authors report Chaetomium globosum as a cause of invasive pulmonary infection in a patient with Wegener's granulomatosis. Fungal hyphae (KOH and Calcofluor) were seen on direct microscopy of lung biopsy sample and bronchoalveolar lavage (BAL) sample. C. globosum isolated on culture clinched the diagnosis of invasive pulmonary infection by Chaetomium spp. A positive galactomannan of serum and BAL was repeatedly seen and was utilised for follow-up and as prognostic marker in patient management. The patient was successfully treated with liposomal amphotericin B followed by voriconazole. All the Chaetomium infections reported till date since 1980 are reviewed. Chaetomium spp. with its unique ecology has a hidden clinical potential to cause invasive mould infections.

Hairy root biotechnology of Rauwolfia serpentina: a potent approach for the production of pharmaceutically important terpenoid indole alkaloids.

Hairy root cultures of Rauwolfia serpentina induced by Agrobacterium rhizogenes have been investigated extensively for the production of terpenoid indole alkaloids. Various biotechnological developments, such as scaling up in bioreactors, pathway engineering etc., have been explored to improve their metabolite production potential. These hairy roots are competent for regenerating into complete plants and show survival and unaltered biosynthetic potential during storage at low temperature. This review provides a comprehensive account of the hairy root cultures of R. serpentina, their biosynthetic potential and various biotechnological methods used to explore the production of pharmaceutically important terpenoid indole alkaloids. The review also indicates how biotechnological endeavors might improve the future progress of research for production of alkaloids using Rauwolfia hairy roots.

NCCP-ICS joint consensus-based clinical practice guidelines on medical thoracoscopy.

ABSTRACT: Medical Thoracoscopy (MT) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. The aim of the study was to provide evidence-based information regarding all aspects of MT, both as a diagnostic tool and therapeutic aid for pulmonologists across India. The consensus-based guidelines were formulated based on a multistep process using a set of 31 questions. A systematic search of published randomized controlled clinical trials, open labelled studies, case reports and guidelines from electronic databases, like PubMed, EmBase and Cochrane, was performed. The modified grade system was used (1, 2, 3 or usual practice point) to classify the quality of available evidence. Then, a multitude of factors were taken into account, such as volume of evidence, applicability and practicality for implementation to the target population and then strength of recommendation was finalized. MT helps to improve diagnosis and patient management, with reduced risk of post procedure complications. Trainees should perform at least 20 medical thoracoscopy procedures. The diagnostic yield of both rigid and semirigid techniques is comparable. Sterile-graded talc is the ideal agent for chemical pleurodesis. The consensus statement will help pulmonologists to adopt best evidence-based practices during MT for diagnostic and therapeutic purposes.

Guidelines for endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA): Joint Indian Chest Society (ICS)/Indian Association for Bronchology (IAB) recommendations.

Over the past decade, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become an indispensable tool in the diagnostic armamentarium of the pulmonologist. As the expertise with EBUS-TBNA has evolved and several innovations have occurred, the indications for its use have expanded. However, several aspects of EBUS-TBNA are still not standardized. Hence, evidence-based guidelines are needed to optimize the diagnostic yield and safety of EBUS-TBNA. For this purpose, a working group of experts from India was constituted. A detailed and systematic search was performed to extract relevant literature pertaining to various aspects of EBUS-TBNA. The modified GRADE system was used for evaluating the level of evidence and assigning the strength of recommendations. The final recommendations were framed with the consensus of the working group after several rounds of online discussions and a two-day in-person meeting. These guidelines provide evidence-based recommendations encompassing indications of EBUS-TBNA, pre-procedure evaluation, sedation and anesthesia, technical and procedural aspects, sample processing, EBUS-TBNA in special situations, and training for EBUS-TBNA.

Radial EBUS-Guided Cryobiopsy of Peripheral Lung Lesions With Flexible Bronchoscopy Without Using Guide-Sheath.

BACKGROUND: A guide-sheath (GS) is conventionally used as a conduit for biopsy forceps under the guidance of radial endobronchial ultrasound (REBUS) for sampling the peripheral pulmonary lesions (PPLs). As compared with forceps, the cryoprobe has the advantage of obtaining larger samples. There is a paucity of literature on the use of cryobiopsy for PPL. We evaluated the diagnostic yield and safety of the REBUS-guided cryobiopsy (REBUS-CB) without using GS for the diagnosis of PPL. METHODS: We retrospectively analyzed the database of 126 patients with PPL between November 2015 and December 2019. The REBUS-CB was performed using a flexible bronchoscopy without GS. Multidisciplinary consensus diagnostic yield was determined and procedural complications were recorded. RESULTS: The histopathologic diagnosis by REBUS-CB, which is the primary objective of the study was obtained in 99 (78.6%) of total 126 cases. Yield was significantly higher in central lesions as compared to adjacent lesions visualized by the REBUS probe (81.4% versus 53.8%, P=0.021) but not significantly different between large (≥30 mm) and small (<30 mm) lesions (81.6% versus 71.8%, P=0.214). The average largest diameter of biopsy specimens was 6.9 mm (range 1-12, SD 2.132). We witnessed moderate bleeding in 7 (5.6%) and post procedure hypoxic respiratory failure in 4 (3.2%) cases which could be managed without escalation of care. CONCLUSION: The REBUS-CB from peripheral lung lesions are feasible even without using GS and significantly large samples can be obtained.

Safety and diagnostic yield of transbronchial lung cryobiopsy by flexible bronchoscopy using laryngeal mask airway in diffuse and localized peripheral lung diseases: A single-center retrospective analysis of 326 cases.

BACKGROUND: Intubation with either an endotracheal tube or a rigid bronchoscope is generally preferred to provide airway protection as well as to manage unpredictable complications during transbronchial lung cryobiopsy (TBLC). The laryngeal mask airway has been described as a safe and convenient tool for airway control during bronchoscopy. AIMS AND OBJECTIVES: In this study, we evaluated the safety and outcome of using a laryngeal mask airway (LMA) as a conduit for performing TBLC by flexible video bronchoscopy (FB). METHODS: We retrospectively analyzed the database of the patients who underwent TBLC between November 2015 and September 2019. The procedure was performed using FB through LMA under general anesthesia. Prophylactic occlusion balloon was routinely used starting January 2017 onwards. Radial endobronchial ultrasound (R-EBUS) guidance was used for TBLC in the localized lung lesions when deemed necessary. Multidisciplinary consensus diagnostic yield was determined and periprocedural complications were recorded. RESULTS: A total of 326 patients were analysed. The overall diagnostic yield was 81.60% (266/326) which included a positive yield of 82.98% (161/194) in patients with diffuse lung disease and 79.54% (105/132) in patients with localized disease. Serious bleeding complication occurred in 3 (0.92%) cases. Pneumothorax was encountered in 8 (2.45%) cases. A total of 9 (2.76%) cases had at least 1 major complication. CONCLUSION: This study demonstrates that the use of LMA during TBLC by flexible bronchoscopy allows for a convenient port of entry, adequate airway support and effective endoscopic management of intrabronchial haemorrhage especially with the use of occlusion balloon.

Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label, multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Global randomised controlled trials of the anti-IL-6 receptor antibody tocilizumab in patients admitted to hospital with COVID-19 have shown conflicting results but potential decreases in time to discharge and burden on intensive care. Tocilizumab reduced progression to mechanical ventilation and death in a trial population enriched for racial and ethnic minorities. We aimed to investigate whether tocilizumab treatment could prevent COVID-19 progression in the first multicentre randomised controlled trial of tocilizumab done entirely in a lower-middle-income country. METHODS: COVINTOC is an open-label, multicentre, randomised, controlled, phase 3 trial done at 12 public and private hospitals across India. Adults (aged ≥18 years) admitted to hospital with moderate to severe COVID-19 (Indian Ministry of Health grading) confirmed by positive SARS-CoV-2 PCR result were randomly assigned (1:1 block randomisation) to receive tocilizumab 6 mg/kg plus standard care (the tocilizumab group) or standard care alone (the standard care group). The primary endpoint was progression of COVID-19 (from moderate to severe or from severe to death) up to day 14 in the modified intention-to-treat population of all participants who had at least one post-baseline assessment for the primary endpoint. Safety was assessed in all randomly assigned patients. The trial is completed and registered with the Clinical Trials Registry India (CTRI/2020/05/025369). FINDINGS: 180 patients were recruited between May 30, 2020, and Aug 31, 2020, and randomly assigned to the tocilizumab group (n=90) or the standard care group (n=90). One patient randomly assigned to the standard care group inadvertently received tocilizumab at baseline and was included in the tocilizumab group for all analyses. One patient randomly assigned to the standard care group withdrew consent after the baseline visit and did not receive any study medication and was not included in the modified intention-to-treat population but was still included in safety analyses. 75 (82%) of 91 in the tocilizumab group and 68 (76%) of 89 in the standard care group completed 28 days of follow-up. Progression of COVID-19 up to day 14 occurred in eight (9%) of 91 patients in the tocilizumab group and 11 (13%) of 88 in the standard care group (difference -3·71 [95% CI -18·23 to 11·19]; p=0·42). 33 (36%) of 91 patients in the tocilizumab group and 22 (25%) of 89 patients in the standard care group had adverse events; 18 (20%) and 15 (17%) had serious adverse events. The most common adverse event was acute respiratory distress syndrome, reported in seven (8%) patients in each group. Grade 3 adverse events were reported in two (2%) patients in the tocilizumab group and five (6%) patients in the standard care group. There were no grade 4 adverse events. Serious adverse events were reported in 18 (20%) patients in the tocilizumab group and 15 (17%) in the standard care group; 13 (14%) and 15 (17%) patients died during the study. INTERPRETATION: Routine use of tocilizumab in patients admitted to hospital with moderate to severe COVID-19 is not supported. However, post-hoc evidence from this study suggests tocilizumab might still be effective in patients with severe COVID-19 and so should be investigated further in future studies. FUNDING: Medanta Institute of Education and Research, Roche India, Cipla India, and Action COVID-19 India.

Scale-Up of Agrobacterium rhizogenes-Mediated Hairy Root Cultures of Rauwolfia serpentina: A Persuasive Approach for Stable Reserpine Production.

Roots of Rauwolfia serpentina, also known as "Sarpagandha" possess high pharmaceutical value due to the presence of reserpine and other medicinally important terpene indole alkaloids. Ever increasing commercial demand of R. serpentina roots is the major reason behind the unsystematic harvesting and fast decline of the species from its natural environment. Considering Agrobacterium rhizogenes-mediated hairy root cultures as an alternative source for the production of plant-based secondary metabolites, the present optimized protocol offers a commercially feasible method for the production of reserpine, the most potent alkaloid from R. serpentina roots. This end-to-end protocol presents the establishment of hairy root culture from the leaf explants of R. serpentina through the infection of A. rhizogenes strain A4 in liquid B5 culture medium and its up-scaling in a 5 L bench top, mechanically agitated bioreactor. The transformed nature of roots was confirmed through PCR-based rol A gene amplification in genomic DNA of putative hairy roots. The extraction and quantification of reserpine in bioreactor grown roots has been done using monolithic reverse phase high-performance liquid chromatography (HPLC).

An unusual case of pleural-based tumor with life-threatening post-operative complication.

A 57-year-old male presented with hemoptysis of 4 years duration and a gradually increasing pleural mass on chest X-ray. The mass was causing pressure effects on the liver and the lungs. To rule out malignancy, thoracotomy was performed, which revealed large, thick-walled hematoma. Complete excision of mass was performed. Post-operative course was complicated by massive pleural bleeding requiring massive blood transfusions and re-exploratory thoracotomy. Subsequent tests revealed factor IX deficiency and, hence, he was managed with recombinant factor IX concentrate. This case stresses upon the fact that hereditary bleeding disorders may be diagnosed even in late adulthood with atypical presentations such as pseudotumor in pleural space. Moreover, hemophilia B may present with normal APTT levels making the diagnosis even more difficult.

Elicitor-induced cellular and molecular events are responsible for productivity enhancement in hairy root cultures: an insight study.

A wide range of external stress stimuli triggers a plant cell to undergo a complex network of reactions that ultimately lead to the synthesis and accumulation of secondary metabolites. These secondary metabolites help the plant to survive under stress challenge. The potential of biotic and abiotic elicitors for the induction and enhancement of secondary metabolite production in various culture systems including hairy root (HR) cultures is well-known. The elicitor-induced defense responses involves signal perception of elicitor by a cell surface receptor followed by its transduction involving some major cellular and molecular events including activation of major secondary message signaling pathways. This result in induction of gene expressions escorting to the synthesis of various proteins mainly associated with plant defense responses and secondary metabolite synthesis and accumulation. The review discusses the elicitor-induced various cellular and molecular events and correlates them with enhanced secondary metabolite synthesis in HR systems. Further, this review also concludes that combining elicitation with in-silico approaches enhances the usefulness of this practice in better understanding and identifying the rate-limiting steps of biosynthetic pathways existing in HRs which in turn can contribute towards better productivity by utilizing metabolic engineering aspects.

A rare presentation of aspergillus infection as empyema thoracis.

A 57-year-old diabetic and hypertensive man presented with a short history of fever, dry cough and right side chest pain. A chest radiograph showed right pleural based homogenous shadow in middle and lower zones with obliteration of right costo-phrenic angle suggestive of right side effusion. Aspiration of pleural fluid revealed frank pus for which inter-costal tube drainage was performed. Due to persistence of empyema, the patient was subjected to thoracoscopy. Thoracoscopy showed multiloculated empyema. Thoracoscopic pleural biopsy and fluid showed septate fungal hyphae. Thoracotomy and parietal pleurectomy, with resection of part of right lower lobe, was carried out. Pleural fluid, pleural and lung tissue culture grew Aspergillus fumigatus. The patient showed good recovery with voriconazole after thoracotomy.

Pattern of Skin Diseases in Urban School Children.

In a survey of 3697 children from 4 urban schools, 529 (14.3%) were found to be having skin diseases. Of these, 286 (53.6%) had communicable dermatomes and nutritional deficiencies. This highlights the importance of imparting proper health education and introduction of mid-day meals to schoolchildren.