Author Response: Beyond the Nasal Prongs: A Joust of Oxygen Delivery Methods in Post-op Hypoxemia.

How to cite this article: Mishra S, Kothari N, Sharma A, Goyal S, Rathod DK, Meshram T, et al. Author Response: Beyond the Nasal Prongs: A Joust of Oxygen Delivery Methods in Post-op Hypoxemia. Indian J Crit Care Med 2024;28(6):626-627.

NK cells modulate in vivo control of SARS-CoV-2 replication and suppression of lung damage.

Natural killer (NK) cells play a critical role in virus control. However, it has remained largely unclear whether NK cell mobilization in SARS-CoV-2 infections is beneficial or pathologic. To address this deficit, we employed a validated experimental NK cell depletion non-human primate (NHP) model with SARS-CoV-2 Delta variant B.1.617.2 challenge. Viral loads (VL), NK cell numbers, activation, proliferation, and functional measures were evaluated in blood and tissues. In non-depleted (control) animals, infection rapidly induced NK cell expansion, activation, and increased tissue trafficking associated with VL. Strikingly, we report that experimental NK cell depletion leads to higher VL, longer duration of viral shedding, significantly increased levels of pro-inflammatory cytokines in the lungs, and overt lung damage. Overall, we find the first significant and conclusive evidence for NK cell-mediated control of SARS-CoV-2 virus replication and disease pathology. These data indicate that adjunct therapies for infection could largely benefit from NK cell-targeted approaches.

Short-Term Outcomes of Patients With Hyponatremia Presenting to the Emergency Department: An Observational Study.

BACKGROUND: Hyponatremia is the predominant electrolyte imbalance disorder in the emergency department. It can manifest with a diverse array of symptoms, ranging from non-specific and moderate to severe and even life-threatening. There is a scarcity of literature addressing the clinical characteristics and prognosis of patients with hyponatremia presenting to the emergency department in the western part of Rajasthan. The objective of this study was to investigate the impact of hyponatremia on the outcomes of patients presenting to the emergency department. METHODS: In this prospective, cross-sectional, observational study, 200 patients aged more than 18 years who presented to the emergency department with serum sodium < 135 mEq/l were included. The triage of patients was determined by their primary complaints. The primary outcome was to study the clinical profile of patients with hyponatremia presenting to the emergency department. The secondary outcomes were to examine the etiology, i.e., hypovolemic, euvolemic, or hypervolemic, and the outcome of patients on the 7th day (patient admitted to the ward or intensive care unit) and the 28th day (discharged or death) with hyponatremia presenting to the emergency department. The clinical status of the patients was noted by telephonic follow-up in case they were not admitted for this period. RESULTS: Out of 200 patients, 66 (33%) had hypovolemic, 96 (48%) had euvolemic, and 38 (19%) had hypervolemic hyponatremia. We observed that seizures (84.2%), confusion (56%), and coma (77.7%) were the most common clinical features of patients with severe hyponatremia in the emergency, which was statistically significant than mild and moderate hyponatremia (p = 0.03, 0.023, and 0.029, respectively). On the 7th day of hospitalization, out of 181 (90.5%) admissions in the ward, 116 (64.08%) had severe hyponatremia, and out of 19 (9.5%) ICU admissions, 13 (68.4%) had severe hyponatremia. Death was seen in five (2.5%) patients, one (20%) in moderate and four (80%) in severe hyponatremia cases. CONCLUSION: Most cases of hyponatremia in this study were euvolemic. Most patients experienced severe hyponatremia, and seizures, confusion, and coma were the most prevalent symptoms. These disorders must be recognized early to properly diagnose and treat hyponatremia and prevent its morbidity and death.

First Insight into the Phylogenetic Diversity of Bovicola caprae Infesting Goats of Different Agro-climatic Locations in India.

Bovicola caprae is an important obligate ectoparasite of goats worldwide including India. The present study aimed at the molecular confirmation, phylogenetics and population structure analyses of B. caprae infesting goats of three different agro-climatic locations in India, by targeting the mitochondrial cytochrome C oxidase subunit 1 (cox1) genetic marker. The phylogenetic tree exhibited the presence of two different lineages of B. caprae. The sequences generated herein clustered in lineage 2 along with the GenBank™ archived sequences from China and Iran. The sequences generated herein also showed the circulation of sub-lineages of B. caprae in India based on the analysis of pairwise genetic distances between sequences and median-joining haplotype network. The population structure analyses revealed low nucleotide (0.00353 ± 0.00291 and 0.02694 ± 0.00363) and high haplotype (0.667 ± 0.314 and 0.618 ± 0.104) diversities for the present study isolates as well as for the complete dataset, respectively, which evinced a recent demographic expansion. High genetic differentiation (FST value = 0.97826) and low gene flow (Nm = 0.00556) were also recorded in the different lineages/populations. In conclusion, the present study addressed the research gap and provided the first insight into the phylogenetics of the goat louse B. caprae and highlighted the circulation of sub-lineages of the ectoparasite in India.

Timing and location dictate monocyte fate and their transition to tumor-associated macrophages.

Tumor-associated macrophages (TAMs) are a heterogeneous population of cells whose phenotypes and functions are shaped by factors that are incompletely understood. Herein, we asked when and where TAMs arise from blood monocytes and how they evolve during tumor development. We initiated pancreatic ductal adenocarcinoma (PDAC) in inducible monocyte fate-mapping mice and combined single-cell transcriptomics and high-dimensional flow cytometry to profile the monocyte-to-TAM transition. We revealed that monocytes differentiate first into a transient intermediate population of TAMs that generates two longer-lived lineages of terminally differentiated TAMs with distinct gene expression profiles, phenotypes, and intratumoral localization. Transcriptome datasets and tumor samples from patients with PDAC evidenced parallel TAM populations in humans and their prognostic associations. These insights will support the design of new therapeutic strategies targeting TAMs in PDAC.

Changes in the Cutaneous Nerve Fiber Staining and Distribution of PGP9.5 in Clinically Uninvolved Skin in Leprosy Patients after Completion of Multidrug Therapy and Assessing PGP9.5 as a Marker of Treatment Response.

Background: Subclinical involvement of nerves may sometimes be present much before the overt clinical manifestations become apparent. Protein gene product (PGP) 9.5, a ubiquitin-C-terminal hydrolase, has been widely used as a marker to study the involvement of peripheral nerve fibers in many diseases. Aim and Objectives: To evaluate the change in cutaneous nerve fiber staining and distribution from pre-treatment and post completion of multidrug therapy through the expression of PGP9.5 and to assess PGP9.5 as a marker of treatment response. Materials and Methods: In this prospective single-center observational study, skin biopsy was taken in patients with leprosy, having areas of nerve function impairment (NFI), based on findings of nerve conduction studies (NCSs), but not having lesions or impaired tactile or thermal impairment clinically. The thin nerve fiber density in the clinically normal skin in areas supplied by nerve showing changes of sensory neuropathy was evaluated to study the density of the fibers. A second biopsy was taken at the end of treatment from a site near the previous site to assess the changes in intra-epidermal nerve fiber staining and distribution. Results: Thirty-three patients were recruited in the present study (24 males and 9 females). Pre-treatment, 27 patients had abnormal NCSs, while six patients did not have any evidence of neuropathy on NCSs. Staining for nerve fibers using PGP9.5; in the epidermis was positive in five patients pre-treatment and 11 patients post treatment (P = 0.181). Staining in the dermis revealed positivity in 14 pre-treatment, which increased to 18 post treatment (P = 0.342). Adnexae showed positivity in five patients pre-treatment and increased to 17 post treatment (P = 0.005). Conclusion: A reduced PGP9.5 staining in the epidermal, dermal, and adnexal regions was seen in leprosy patients, which improved post treatment. Thus, PGP9.5 may serve as a marker of NFI and treatment response.

Lipoplexes' Structure, Preparation, and Role in Managing Different Diseases.

Lipid-based vectors are becoming promising alternatives to traditional therapies over the last 2 decades specially for managing life-threatening diseases like cancer. Cationic lipids are the most prevalent non-viral vectors utilized in gene delivery. The increasing number of clinical trials about lipoplex-based gene therapy demonstrates their potential as well-established technology that can provide robust gene transfection. In this regard, this review will summarize this important point. These vectors however have a modest transfection efficiency. This limitation can be partly addressed by using functional lipids that provide a plethora of options for investigating nucleic acid-lipid interactions as well as in vitro and in vivo nucleic acid delivery for biomedical applications. Despite their lower gene transfer efficiency, lipid-based vectors such as lipoplexes have several advantages over viral ones: they are less toxic and immunogenic, can be targeted, and are simple to produce on a large scale. Researchers are actively investigating the parameters that are essential for an effective lipoplex delivery method. These include factors that influence the structure, stability, internalization, and transfection of the lipoplex. Thorough understanding of the design principles will enable synthesis of customized lipoplex formulations for life-saving therapy.

A Systematic Review of Radiological Diagnosis and Management of May-Thurner Syndrome.

May-Thurner syndrome (MTS) is an anatomical condition of external luminal compression of common iliac vein due to a partial obstruction of the common iliac vein between common iliac artery and lumbar vertebra causes deep-vein thrombosis, venous hypertension, and chronic venous insufficiencies. In this article, we review present evidence of the clinical diagnosis and management of MTS. Here, we conducted a literature review of studies on MTS. We also reviewed different clinical features, presentation, diagnostic methods, and therapeutic procedure for this condition. Most studies mentioned the diagnosis of this condition is performed by color Doppler, computed tomographic angiography, venography, and problem-solving cases by intravascular ultrasound technique. Nonsurgical methods of management are first line, and vascular surgery is reserved for refractory cases. Multiple modalities are required to reach the diagnosis of MTS, and noninvasive intervention radiology methods are the first line of management. This review highlights the presentations of MTS and outlines diagnostic procedure and management.

Evaluation of Shoulder Injuries: A Comparative Study of Imaging by Magnetic Resonance Imaging (MRI) and Magnetic Resonance Arthrography (MRA).

Background: In contrast to the standard shoulder arthroscopy, current radio-diagnostic techniques like magnetic resonance arthrography (MRA), and magnetic resonance imaging (MRI) provide less invasive intricate structural detail of shoulder anatomy. Objectives: Comparison of efficacy of MRA and MRI for diagnosing suspected rotator cuff injury. Materials and Methods: Over the course of 4 years (from June 2017 to June 2021), a comparative study, including 100 individuals with suspected rotator cuff pathology, was conducted. For the evaluation of shoulder injuries, the assessment and comparison of MRA and MRI were done in terms of sensitivity (Sn), positive predictive value (PPV), and diagnostic accuracy (DA). Results: MRI and MRA were positive in 76 (76%) and 98 (98%) patients, respectively. The Sn and PPV of MRI for diagnosing the shoulder injury were 76% and 100%, respectively, whereas the Sn and PPV of MRA were 98% and 100%, respectively. MRA was better than MRI in terms of diagnostic accuracy (98% vs. 76%, P = 0.03). Conclusion: MRA is a nonsurgical effective method in evaluating and diagnosing rotator cuff injuries in comparison to MRI.

Comparison of midpoint transverse process to pleura (MTP) block and erector spinae plane block (ESP) for postoperative analgesia in modified radical mastectomy patients: A double-blinded, randomized control trial.

Background and Aims: Modified radical mastectomy (MRM) is associated with moderate severity of postoperative pain. Besides intravenous (IV) analgesics, various nerve blocks are being described for pain relief of MRM patients. We compared erector spinae plane (ESP) block with midpoint transverse process to pleura (MTP) block in these patients for postoperative analgesia. Material and Methods: After receiving ethical committee approval from the institutional ethics committee (AIIMS, Jodhpur) and written informed consent from study participants, 66 patients who were assigned American Society of Anesthesiologists (ASA) physical status I and II, aged 18-75 years, and were scheduled to undergo MRM were enrolled and randomly allocated into two groups. Unilateral block was given before surgery at T3 or T4 level and with 15 ml of 0.5% ropivacaine in both the groups. Infusion of 0.5% ropivacaine (Neon laboratories limited, Mumbai, India) and 0.2% ropivacaine at a rate of 5 ml/h was maintained intraoperatively and postoperatively, respectively. Pain was assessed using the Visual Analogue Scale (VAS) for the next 24 hours. The total number of patients needing rescue analgesia, the total amount of rescue analgesics consumed in the next 24 hours, and patient satisfaction score were also compared between groups. Results: Demographics and baseline vitals were comparable in the groups. On comparing VAS scores in both the groups during rest and movement at different time intervals, there was no difference in pain scores during the initial two hours. From the third hour, there was a statistically significant difference (P < 0.001) in pain VAS scores in both groups. The ESP group had lower VAS scores compared to the MTP group when followed for the next 24 hours. There was a statistically significant difference in patient satisfaction. Conclusion: ESP block is more efficacious when compared to MTP block for postoperative analgesia in MRM patients.

Correction: Gill et al. Report from the 24th Annual Western Canadian Gastrointestinal Cancer Consensus Conference on Colorectal Cancer, Richmond, British Columbia, 28-29, October 2022. Curr. Oncol. 2023, 30, 7964-7983.

Karen Mulder was not included as an author in the original publication [...].

Safety and complications of labour epidural analgesia in obese parturients: worrying is not worth the weight!

The physiological transformations accompanying pregnancy, compounded by the implications of obesity, pose intricate challenges for anaesthesiologists attending to obese parturients. Obesity makes it harder to successfully provide epidural analgesia to a parturient. This narrative review explains the most recent data on the safety and complications of providing labour epidural analgesia in obese expectant mothers. We have emphasised the evidence-based approaches that are the most effective for obese pregnant mothers receiving labour epidural analgesia.

Utility of Pulmonary Angiography by 128-Slice Computed Tomographic Scanner in Diagnosis of Tetralogy of Fallot Cases.

Tetralogy of Fallot (TOF) is a significant cause of cyanotic congenital heart disease (CHD) encountered in childhood with few cases manifesting in adulthood. It has four classical features (ventricular septal defect, overriding of aorta, hypertrophy of right ventricular hypertrophy, and right ventricular outflow tract obstruction), but the clinical presentation and course can be variable. Due to various anatomical variations and complex anatomy, presurgical planning and postoperative follow-up by pulmonary computed tomographic angiography (CTA) have a very important role. With continued technological advances and the availability of 128-slice computed tomographic (CT) scans, they now play an important role in TOF preoperative evaluation and workup, assisting by minimizing routine invasive digital subtraction catheter angiography. The fast scan of a 128-slice CTA with very sensitive detectors is a very useful modality for studying the complex anatomy and variations as well as its utilization for postoperative management. In this article, we report four cases of TOF where we used a 128-slice scan for performing pulmonary angiography (Optima 660, GE 128, 2180 Premier Row, Orlando, FL 32809, U.S.A.) for preoperative diagnosis and management of three cases and work up for revision surgery for an already operated case with a nonfunctional modified Blalock-Taussig shunt with additional lung parenchymal findings simultaneously. This study will explain the advantageous role of the 128-slice CT scanner over the lesser-slice CT scanners with the ability of pulmonary CTA to facilitate accurate diagnosis and postoperative management.

Analgesic efficacy of classical thoracolumbar interfascial plane block versus modified thoracolumbar interfascial plane block in patients undergoing lumbar disc surgeries: A comparative, randomised controlled trial.

Background and Aims: We compared classical (medial) and modified (lateral) thoracolumbar interfascial plane block (TLIP) with only general anaesthesia (GA) using multimodal analgesia in patients undergoing lumbar disc surgeries. Methods: In this study, 100 patients aged 18-70 years were randomised to Group cTLIP (conventional TLIP block with 20 mL of 0.25% ropivacaine with GA), Group mTLIP (modified TLIP block with 20 mL of 0.25% ropivacaine with GA), and Group C (only GA using multimodal analgesia). The primary outcome was to assess the total peri-operative opioid consumption in the first 24 h. The secondary outcomes were to assess pain score upon arriving in the post-anaesthesia care unit, time to first analgesic need after surgery, post-operative opioid consumption in 24 h, and incidence of nausea and vomiting. Results: The total peri-operative opioid consumption in Group cTLIP (507.58 (258.55) µg) and Group mTLIP (491.67 (165.39) µg) was significantly lower than that in Group C (1225.4 (237.03) µg); (P < 0.001). However, it was comparable between groups cTLIP and mTLIP (P = 0.767). Pain score was comparable in groups cTLIP and mTLIP. It was significantly lower than Group C (P = 0.001). Rescue analgesia was needed in all (100%) patients of Group C but in only 15.2% of patients of the cTLIP and mTLIP groups. No patient in groups cTLIP and mTLIP complained of nausea and vomiting in the first 24 h, whereas it was significantly higher (61.8%) in Group C (P = 0.001). Conclusion: The analgesic effect of the modified TLIP block was not superior to the conventional TLIP block. Both techniques provided the same intra-operative and post-operative analgesia for lumbar disc surgeries.

A rare case of huge frontoethmoidal encephalocele projecting through mouth, with cleft palate.

Frontoethmoidal encephalocele represents protrusion of meninges and brain in a sac through a defect in the anterior skull base, mostly as swelling over the nose. Rarely it is associated with facial dysmorphism and palatal cleft. There are various perioperative concerns like airway difficulties, leaking from the swelling causing fluid and electrolyte disturbances, risk of infection, compression of the swelling causing a rise in intracranial pressure, bleeding, hypothermia, etc., In neonates, these challenges rise exponentially because of the inherent difficulties in dealing with this group of patients. Frontoethmoidal encephaloceles are common in low socioeconomic strata and are often missed in the antenatal period. We are reporting a rare case of frontoethmoidal encephalocele, with a huge swelling protruding through the cleft palate and occupying more than 50% of the face and oral cavity, making mask ventilation impossible.

Aerosol drug therapy in critically ill patients (Aero-in-ICU study): A multicentre prospective observational cohort study.

BACKGROUND: In recent years, a significant understanding of delivering optimal aerosol therapy and the availability of various drugs and devices have led to an increase in its use in clinical practice. There are only a few studies available regarding their use in critically ill patients from a few parts of the world. We aimed to study the practice pattern of aerosol therapy in critically ill patients from Indian intensive care units (ICUs). METHODS: After ethical approval, this multi-centric prospective observational study was performed over a study period of four weeks. Newly admitted adult patients considered who had an artificial airway and/or ventilation (including non-invasive). Patients were followed up for the next 14 days or until ICU discharge/death (whichever came first) for details of each aerosol therapy, including ongoing respiratory support, drug type, and aerosol-generating device. RESULTS: From the nine participating centers across India, 218 patients were enrolled. Of 218 enrolled patients, 72.48% received 4884 aerosols with 30.91 ± 27.15 (95%CI: 26.6-35.1) aerosols per patient over 1108 patient days. Approximately 62.7% during IMV, 30.2% during NIV, 2.3% in spontaneously breathing patients with an artificial airway during weaning, and 4.7% were given without an artificial airway after weaning or decannulation. In 59%, a single drug was used, and bronchodilators were the most frequent. The jet nebulizer was the most common, followed by the ultrasonic and vibrating mesh aerosol generator. The ventilator setting was changed in only 6.6% of the aerosol sessions with IMV and none with NIV. CONCLUSION: Aerosol therapy is frequently used with a wide variation in practices; bronchodilators are the most commonly used drugs, and jet nebulizers are the most widely used.

Comparison of Oxygen Delivery Devices in Postoperative Patients with Hypoxemia: An Open-labeled Randomized Controlled Study.

Background: Acute hypoxemic respiratory failure is among the more commonly occurring complications in postoperative patients. Supplemental oxygen and addressing the primary etiology form the basis of its treatment. Materials and methods: We conducted an open-labeled randomized control trial with 90 adult patients and compared three oxygen delivery vehicles (ODV), i.e., noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and venturi mask (VM) in postoperative hypoxemic patients. The primary outcome variable was a change in the P/F ratio after 2 hours of use of ODV. Results: It was observed that the change in P/F ratio after 2 hours was similar in all three ODV groups (p = 0.274). The mean values of the post-ODV P/F ratio were comparable with the pre-ODV P/F ratio in all three modalities. The P/F ratio after HFNC was 358.08 ± 117.95; after NIV was 357.60 ± 220.67; and after VM was 355.47 ± 101.90 (p = 0.997). Conclusion: Among HFNC, NIV, and VM, none of the devices proved superior to the other for use in postoperative hypoxemia. How to cite this article: Mishra S, Kothari N, Sharma A, Goyal S, Rathod D, Meshram T, et al. Comparison of Oxygen Delivery Devices in Postoperative Patients with Hypoxemia: An Open-labeled Randomized Controlled Study. Indian J Crit Care Med 2024;28(3):294-298.

Exploring promising natural compounds for breast cancer treatment: in silico molecular docking targeting WDR5-MYC protein interaction.

Cancer is an aberrant differentiation of normal cells, characterized by uncontrolled growth and the potential to acquire invasive and aggressive properties that ultimately lead to metastasis. In the realm of scientific exploration, a multitude of pathways has been investigated and targeted by researchers, among which one specific pathway is recognized as WDR5-MYC. Continuous investigations and research show that WDR5-MYC is a therapeutic target protein. Hence, the discovery of naturally occurring compounds with anticancer properties has been suggested as a rapid and efficient alternative for the development of anticancerous therapeutics. A virtual screening approach was used to identify the most potent compounds from the NP-lib database at the MTiOpenScreen webserver against WDR5-MYC. This process yielded a total of 304 identified compounds. Subsequently, after screening, four potent compounds, namely Estrone (ZINC000003869899), Ethyl-1,2-benzanthracene (ZINC000003157052), Strychnine (ZINC000000119434) and 7H-DIBENZO [C, G] CARBAZOLE (ZINC000001562130), along with a cocrystallized 5-[4-(trifluoromethyl) phenyl]-1H-tetrazole inhibitor (QBP) as a reference ligand, were considered for stringent molecular docking. Thus, each compound exhibited significant docking energy between -8.2 and -7.7 kcal/mol and molecular contacts with essential residue Asn225, Lys250, Ser267 and Lys272 in the active pocket of WDR5-MYC against the QBP inhibitor (the native ligand QBP serves as a reference in the comparative analysis of docked complexes). The results support the potent compounds for drug-likeness and strong binding affinity with WDR5-MYC protein. Further, the stability of the selected compounds was predicted by molecular dynamics simulation (100 ns) contributed by intermolecular hydrogen bonds and hydrophobic interactions. This demonstrates the potential of the selected compounds to be used against breast cancer treatment.Communicated by Ramaswamy H. Sarma.

Investigating the dynamic nature of landslide susceptibility in the Indian Himalayan region.

Landslide susceptibility zonation (LSZ) mapping is used to delineate areas prone to landslides and is critical for effective landslide hazard management. The existing methodologies for generating such maps tend to neglect the influence of dynamic environmental variables on landslide occurrences, which may lead to obsolete and erroneous estimates of landslide susceptibility (LS) for a concerned area. Although recent studies have started to report the effects of Land Use/ Land Cover (LULC) variation on LSZ mapping, variations in other dynamic variables like rainfall, soil moisture, and evapotranspiration apart from LULC may also influence slope stability in mountainous regions. The present study investigates the impact of variations in these four variables on the LS distribution, of a selected Indian Himalayan region between 2017 and 2021. Random Forest (RF) susceptibility models are utilized for evaluating the LS for the selected years and geospatial technologies are employed for LS change detection. The results indicate up to 19% variations in the spatial extent for some of the zones of the generated LSZ maps. The research findings of this study are crucial since they reveal the impact of dynamic behavior on LS, which has not been previously documented in the literature.