Impacts of oxidative stress and anti-oxidants on the development, pathogenesis, and therapy of sickle cell disease: A comprehensive review.

Sickle cell disease (SCD) is the most severe monogenic hemoglobinopathy caused by a single genetic mutation that leads to repeated polymerization and depolymerization of hemoglobin resulting in intravascular hemolysis, cell adhesion, vascular occlusion, and ischemia-reperfusion injury. Hemolysis causes oxidative damage indirectly by generating reactive oxygen species through various pathophysiological mechanisms, which include hemoglobin autoxidation, endothelial nitric oxide synthase uncoupling, reduced nitric oxide bioavailability, and elevated levels of asymmetric dimethylarginine. Red blood cells have a built-in anti-oxidant system that includes enzymes like sodium dismutase, catalase, and glutathione peroxidase, along with free radical scavenging molecules, such as vitamin C, vitamin E, and glutathione, which help them to fight oxidative damage. However, these anti-oxidants may not be sufficient to prevent the effects of oxidative stress in SCD patients. Therefore, in line with a recent FDA request that the focus to be placed on the development of innovative therapies for SCD that address the root cause of the disease, there is a need for therapies that target oxidative stress and restore redox balance in SCD patients. This review summarizes the current state of knowledge regarding the role of oxidative stress in SCD and the potential benefits of anti-oxidant therapies. It also discusses the challenges and limitations of these therapies and suggests future directions for research and development.

Hospitalization Events Among Adolescents and Adults With Sickle Cell Disease in a Tertiary Care Center in Central India.

BACKGROUND: Sickle cell disease (SCD) is an inherited red blood cell disorder, wherein mutation causes the substitution of glutamic acid to valine at the sixth position of the ß-globin chain. These include sickle cell anemia (homozygous sickle mutation), sickle-beta thalassemia, and hemoglobin SCD. The clinical manifestations of SCD are protean. Individuals with SCD suffer from both acute and chronic complications, which include recurring episodes of pain commonly called vaso-occlusive crisis (VOC) - acute chest syndrome (ACS); aseptic necrosis of the bone; micro-infarction of the spleen, brain, and kidney; infections; stroke; and organ damage affecting every part of the body. SCD necessitates frequent hospitalizations because of severe complications, which pose a significant burden on caregivers and economic strain on healthcare systems. The pattern of hospital admission with SCD varies in different parts of the world. OBJECTIVE: This study aimed to determine the causes of hospitalization among adolescent and adult patients with SCD and to determine factors associated with their hospital stay. METHODS: The study was a hospital-based prospective observational study comprising adolescent and adult patients diagnosed with SCD, aged 15-45 years, who were hospitalized in the Department of General Medicine at All India Institute of Medical Sciences in Raipur from August 2021 to August 2022. RESULT: According to our study, the primary reason for hospitalization was a painful crisis, accounting for 63% of cases, followed by infection (17%), ACS (11%), and acute hemolytic crisis (9%). Notably, we did not observe any significant differences between genders and causes of admission (p > 0.05). Joint pain (p = 0.005), back pain (p = 0.001), and chest pain (p = 0.001) were more frequently reported by adults over the age of 19. In addition, our analysis of the duration of hospital stays and various factors revealed that patients admitted for infections had a significantly longer mean hospital stay duration (p = 0.040). CONCLUSION: Acute painful crises were the primary cause of hospital admission among individuals with SCD; many patients also encountered infections and ACS. Furthermore, patients who experienced infections and VOC had a lengthier duration of hospital stay. Therefore, it is essential to provide them with comprehensive instructions on various preventive measures against infections and the factors that trigger painful crises.

Phytosynthesis and characterization of tin-oxide nanoparticles (SnO2-NPs) from Croton macrostachyus leaf extract and its application under visible light photocatalytic activities.

Nanotechnology is rapidly becoming more and more important in today's technological world as the need for industry increases with human well-being. In this study, we synthesized SnO2 nanoparticles (NPs) using an environmentally friendly method or green method from Croton macrostachyus leaf extract, leading to the transformation of UV absorbance to visible absorbance by reducing the band gap energy. The products underwent UV, FTIR, XRD, SEM, EDX, XPS, BET, and DLS for characterization. Characterization via UV-Vis spectroscopy confirmed the shift in absorbance towards the visible spectrum, indicating the potential for enhanced photocatalytic activity under visible light irradiation. The energy band gap for as-synthesized nanoparticles was 3.03 eV, 2.71 eV, 2.61 eV, and 2.41 eV for the 1:1, 1:2, 1:3, and 1:4 sample ratios, respectively. The average crystal size of 32.18 nm and very fine flakes with tiny agglomerate structures of nanoparticles was obtained. The photocatalytic activity of the green-synthesized SnO2 nanoparticles was explored under visible light irradiation for the degradation of rhodamine B (RhB) and methylene blue (MB), which were widespread fabric pollutants. It was finally confirmed that the prepared NPs were actively used for photocatalytic degradation. Our results suggest the promising application of these green-synthesized SnO2 NPs as efficient photocatalysts for environmental remediation with low energy consumption compared to other light-driven processes. The radical scavenging experiment proved that hydroxyl radicals (_OH) are the predominant species in the reaction kinetics of both pollutant dyes under visible light degradation.

Kisspeptin stimulates oestradiol biosynthesis by upregulating steroidogenic transcripts and proliferation markers in the bubaline granulosa cells in vitro.

Kisspeptin (Kp), an upstream regulator of GnRH release, is essential for the development and function of reproductive axis. Previously, we demonstrated the localization of Kp and its receptor (Kiss1r) in the active follicle in the bubaline ovary. Present study aimed to determine the effect of Kp on granulosa cell (GCs) functions, especially oestradiol (E2 ) and progesterone (P4 ) production, and differential expression of genes regulating the proliferation, apoptosis and steroidogenesis in the buffalo. The ovaries with 6-10 mm size follicles obtained from the cyclic buffaloes after slaughtering were used for isolation of GCs for in vitro study. The primary GCs culture was treated with Kp (0, 10, 50 and 100 nM) and incubated for 48 h. Production of E2 and P4 was estimated in the culture supernatant by ELISA. The expression of gonadotropin receptors (FSHR and LHR), steroidogenic genes (STAR, 3ß-HSD, CYP19A1), proliferation marker (PCNA), apoptotic factors (CASP3 and BCL2) and Kp signalling molecule (extracellular signal-regulated kinase 1/2, ERK1/2 and p-ERK1/2) was studied in the GCs by qPCR. Significant E2 production was found in the Kp 50 and 100 nM groups (p < .05), whereas P4 production was reduced in Kp 100 nM group (p < .05). There was concomitant upregulation of FSHR, ERK1/2, STAR and CYP19A1 in the Kp 100 nM treated GCs. In addition, Kp at 100 nM stimulated the proliferation of GCs by upregulating the expression of BCL2 (5.0 fold) and PCNA (94.9 fold). Further, high immunoreactivity of p-ERK1/2 was observed in the Kp-treated GCs. It was concluded that Kp at 100 nM concentration stimulated E2 production by upregulating the steroidogenic pathway through ERK1/2, STAR and CYP19A1 and modulating PCNA and BCL2 expressions in the GCs. Further experiments are warranted using Kp antagonist in different combinations to establish the signalling pathway in Kp-mediated steroidogenesis in the GCs for developing strategies to control ovarian functions.

Management of SARS-CoV-2 infection is a major challenge in patients with lymphoid malignancies: Warrants a clear therapeutic strategy.

Patients with lymphoid malignancies are at a higher risk of coronavirus disease 2019 (COVID-19) infection due to their immunocompromised state and results in higher mortality rates in these patients. Anti-CD 20 therapy is one of the leading causes of immunosuppression that worsens in COVID-19 cases. COVID-19 vaccines, on the other hand, appear to be less beneficial to these patients. App-ropriate treatment and recommendations are required for these COVID-19 patients with lymphoid malignancies.

Liver dysfunction during COVID-19 pandemic: Contributing role of associated factors in disease progression and severity.

In December 2019, a new strain of coronavirus was discovered in China, and the World Health Organization declared it a pandemic in March 2020. The majority of people with coronavirus disease 19 (COVID-19) exhibit no or only mild symptoms such as fever, cough, anosmia, and headache. Meanwhile, approximately 15% develop a severe lung infection over the course of 10 d, resulting in respiratory failure, which can lead to multi-organ failure, coagulopathy, and death. Since the beginning of the pandemic, it appears that there has been consideration that pre-existing chronic liver disease may predispose to deprived consequences in conjunction with COVID-19. Furthermore, extensive liver damage has been linked to immune dysfunction and coagulopathy, which leads to a more severe COVID-19 outcome. Besides that, people with COVID-19 frequently have abnormal liver function, with more significant elevations in alanine aminotransferase and aspartate aminotransferase in patients with severe COVID-19 compared to those with mild/moderate disease. This review focuses on the pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the liver, as well as the use of liver chemistry as a prognostic tool during COVID-19. We also evaluate the findings for viral infection of hepatocytes, and look into the potential mechanisms behind SARS-CoV-2-related liver damage.

Safety and Feasibility of AnaConDa™ to Deliver Inhaled Isoflurane for Sedation in Patients Undergoing Elective Postoperative Mechanical Ventilation: A Prospective, Open-label, Interventional Trial (INSTINCT I Study).

Aim: Sedation is essential during invasive mechanical ventilation, and conventionally intravenous analgesic and sedative drugs are used. Sedation with inhaled anesthetics using anesthesia conserving device (ACD) is an alternative. There is no data on the safety and ease of use of AnaConDa™ from India. Materials and methods: After IEC approval and informed consent, we used AnaConDa™-S for Isoflurane sedation in 50 hemodynamically stable (need for <0.5 µg/kg/min of Noradrenaline infusion), ASA I and II patients aged 18-80 years, undergoing elective mechanical ventilation for up to 24 hours after elective oncosurgeries. Patients with mental obtundation (GCS <14), or if pregnant, were excluded. The primary outcome was time spent between RASS scores of -3 and -4, while secondary outcomes were incidence of delirium, technical problems with AnaConDa™, and adverse systemic effects of isoflurane. Bolus doses of isoflurane 0.2-0.5 mL were given if the Richmond agitation sedation scale (RASS) score was not achieved. Results: Fifty patients received isoflurane infusion for a median of 720 (IQR 630-900) minutes, and all remained in the target sedation range. Median time to awakening [19 (IQR, 5-85) minutes], to follow simple verbal commands [20 (IQR 5-180) minutes], and extubation after stopping the infusion of isoflurane was quick [100 (10-470) minutes]. All patients remained hemodynamically stable. None of the patients had delirium. Conclusion: Target sedation levels were achieved with initial boluses of isoflurane using AnaConDa™-S. Isoflurane sedation delivery using AnaConDa™-S is safe and feasible. How to cite this article: Kulkarni AP, Bhosale SJ, Kalvit KR, Sahu TK, Mohanty R, Dhas MM, et al. Safety and Feasibility of AnaConDa™ to Deliver Inhaled Isoflurane for Sedation in Patients Undergoing Elective Postoperative Mechanical Ventilation: A Prospective, Open-label, Interventional Trial (INSTINCT I Study). Indian J Crit Care Med 2022;26(8):906-912.

Bacterial and fungal co-infection is a major barrier in COVID-19 patients: A specific management and therapeutic strategy is required.

Microbial co-infections are another primary concern in patients with coronavirus disease 2019 (COVID-19), yet it is an untouched area among researchers. Preliminary data and systematic reviews only show the type of pathogens responsible for that, but its pathophysiology is still unknown. Studies show that these microbial co-infections are hospital-acquired/nosocomial infections, and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it. Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response, with lower CD4+ T and CD8+ T cell counts, indicating vulnerability to various co-infections. Despite this, there are only a few studies that recommend the management of co-infections.

Neurocognitive Changes in Sickle Cell Disease: A Comprehensive Review.

Background: Sickle cell disease (SCD) is a type of hemoglobinopathy characterized by abnormal hemoglobin molecules, which includes numerous acute and chronic complications. Ischemic stroke, silent cerebral infarction, headache, and neurocognitive impairment are the most common neurological complications associated with SCD. Summary: Acute anemia because of SCD can cause cognitive impairments because of cerebral hypoxia. Cognitive abnormalities in SCD manifest in various aspects such as working memory, verbal learning, executive functions, and attention. These neurocognitive impairments have been associated with poor functional results, such as transitioning from juvenile to adult care, adherence to medications, and unemployment. Key message: In this review, we focus on neurocognitive aspects of SCD patients based on different imaging techniques, psychological batteries, associated neuromarkers, and interventions for managing of cognitive deficiencies..

Common, But Neglected: A Comprehensive Review of Leg Ulcers in Sickle Cell Disease.

OBJECTIVE: To compile available evidence to better understand the management of leg ulcers in sickle cell disease (SCD), as well as describe potential therapeutic steps that may be required to improve the quality of life of patients with SCD leg ulcers. DATA SOURCES: MEDLINE, PubMed, EMBASE, and Web of Science databases. STUDY SELECTION: A comprehensive search was conducted to retrieve relevant studies using the keywords "sickle cell disease and leg ulcer," "ulcer treatments, diagnosis and sickle cell," and "wound sickle cell." Studies published through July 2020 were included. DATA EXTRACTION: Two independent authors selected all studies that assessed the relationship between leg ulcer and SCD identified from online databases. DATA SYNTHESIS: The authors have summarized updated information on pathophysiology (vasculopathy linked to chronic hemolysis and endothelial dysfunction), diagnosis, and available treatment options to unravel the dermohematologic connection between leg ulcers and SCD. CONCLUSIONS: It is the authors' hope that this detailed discussion of the information available on leg ulcers and SCD will lead to a better appreciation of this clinical problem by the clinicians and researchers and in turn have a long-term positive effect on the quality of life of patients with SCD. Researchers should design new trials considering these insights and potential therapeutic approaches based on current knowledge.

Current understanding of the impact of COVID-19 on gastrointestinal disease: Challenges and openings.

The novel coronavirus disease-2019 (COVID-19) is caused by a positive-sense single-stranded RNA virus which belongs to the Coronaviridae family. In March 2019 the World Health Organization declared that COVID-19 was a pandemic. COVID-19 patients typically have a fever, dry cough, dyspnea, fatigue, and anosmia. Some patients also report gastrointestinal (GI) symptoms, including diarrhea, nausea, vomiting, and abdominal pain, as well as liver enzyme abnormalities. Surprisingly, many studies have found severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA in rectal swabs and stool specimens of asymptomatic COVID-19 patients. In addition, viral receptor angiotensin-converting enzyme 2 and transmembrane protease serine-type 2, were also found to be highly expressed in gastrointestinal epithelial cells of the intestinal mucosa. Furthermore, SARS-CoV-2 can dynamically infect and replicate in both GI and liver cells. Taken together these results indicate that the GI tract is a potential target of SARS-CoV-2. Therefore, the present review summarizes the vital information available to date on COVID-19 and its impact on GI aspects.

Procedures in COVID-19 Patients: Part-I.

The number of cases with novel coronavirus disease-2019 (COVID-19) infection is increasing every day in the world, and India contributes a substantial proportion of this burden. Critical care specialists have accepted the challenges associated with the COVID-19 pandemic and are frontline warriors in this war. They have worked hard in streamlining workflow isolation of positive patients, clinical management of critically ill patients, and infection prevention practices. With no end in sight for this pandemic, intensive care unit (ICU) practitioners, hospital administrators, and policy makers have to join hands to prepare for the surge in critical care bed capacity. In this position article, we offer several suggestions on important interventions to the ICU practitioners for better management of critically ill patients. This position article highlights key interventions for COVID-19 treatment and covers several important issues such as endotracheal intubation and tracheostomy (surgical vs PCT), nebulization, bronchoscopy, and invasive procedures such as central venous catheters, arterial lines, and HD catheters. How to cite this article: Pande RK, Bhalla A, SN Myatra, Yaddanpuddi LN, Gupta S, Sahoo TK, et al. Procedures in COVID-19 Patients: Part-I. Indian J Crit Care Med 2020;24(Suppl 5):S263-S271.

Procedures in COVID-19 Patients: Part-II.

Critical care in the era of novel coronavirus disease-2019 (COVID-19) infection has multiple challenges including management of the patient, underlying comorbidities, and the complications. With no end in sight to the pandemic, intensive care unit (ICU) practitioners and hospital administrators have to join hands to prepare for the long battle ahead. Critically ill COVID-19 patients need imaging or image-guided interventions in one form or the other including X-rays, ultrasonography (USG), echocardiography (ECHO), and CT scan. These patients often require renal replacement therapy (RRT) for either the preexisting chronic renal insufficiency or acutely developing kidney injury. Another important component of care is transfer of the patient to and fro from the ICU or to higher care centers. Most of the ICUs are equipped with modern facilities but with increasing number of patients a large number of makeshift arrangements are being made for managing these patients. This position paper outlines important tips to formulate protocols and procedures for critically ill patients, who are managed in the ICU. How to cite this article: Pande RK, Bhalla A, Myatra SN, Yaddanpuddi LN, Gupta S, Sahoo TK, et al. Procedures in COVID-19 Patients: Part-II. Indian J Crit Care Med 2020;24(Suppl 5):S272-S279.