A systematic review and meta-analysis of diagnostic performance of fluorescein-guided sentinel lymph node biopsy in early breast cancer.

BACKGROUND: Evaluation of axillary lymph nodes status in cN0 axilla is performed by sentinel lymph node biopsy (SLNB) utilizing a combination of radioactive isotope and blue dye or alternative to isotope like Indocyanine green (ICG). Both are very resource-intensive; which has prompted development of low-cost technique of Fluorescein Sodium (FS)-guided SLNB. This systematic review and meta-analysis evaluate the diagnostic performance of FS-guided SLNB in early breast cancer. OBJECTIVES: The objective was to evaluate the diagnostic performance of FS for sentinel lymph node biopsy. METHODS: Eligibility criteria: Studies where SLNB was performed using FS. INFORMATION SOURCES: PubMed, EMBASE, Cochrane library and online clinical trial registers. Risk of bias: Articles were assessed for risk of bias using the QUADAS-2 tool. SYNTHESIS OF RESULTS: The main summary measures were pooled Sentinel Lymph Node Identification Rate (SLN-IR) and pooled False Negative Rate (FNR) using random-effects model. RESULTS: A total of 45 articles were retrieved by the initial systematic search. 7 out of the 45 studies comprising a total of 332 patients were included in the meta-analysis. The pooled SLN-IR was 93.2% (95% confidence interval [CI], 0.87-0.97; 87% to 97%). Five validation studies were included for pooling the false negative rate and included a total of 211 patients. The pooled FNR was 5.6% (95% confidence interval [CI], 2.9-9.07). CONCLUSION: Fluorescein-guided SLNB is a viable option for detection of lymph node metastases in clinically node negative patients with early breast cancer. It achieves a high pooled Sentinel Lymph Node Identification Rate (SLN-IR) of 93% with a false negative rate of 5.6% for the detection of axillary lymph node metastasis.

Theoretical analysis of graded-index topological resonator for improved sensing performance.

In this manuscript, what we believe to be a novel hyperbolic-graded topological nano-photonic resonator structure is proposed to excite robust topological edge states. The graded refractive index is realized by considering a porous silicon material having a deliberately modulated local refractive index. The introduction of grading effectively modifies its dispersion characteristics leading to distinctive topological properties. This results in excitation of a topologically protected edge state (TES) having significantly higher interface electric field intensity at an operational wavelength of 1521 nm. Additionally, the impact of interface layer thicknesses on the excitation of these TES is thoroughly investigated. Finally, the structure's capability to be used as a refractive index sensor is also demonstrated. The analytical results demonstrate an average sensitivity of 852.14 nm/RIU, coupled with a quality factor of 4019.23 and a figure of merit (FOM) of 1277.13 RIU-1. With its remarkable performance metrics, the proposed device holds significant promise for accurately detecting and sensing biochemical samples with very high efficiency.

Predicting intracranial involvement: Unveiling perineural spread in COVID-19-associated mucormycosis, a novel phenomenon.

This study aimed to investigate the risk factors associated with intracranial involvement in COVID-19-associated mucormycosis (CAM) and to develop a nomogram model for predicting the risk of intracranial involvement, with a specific focus on perineural spread. An ambispective analysis was conducted on 275 CAM patients who received comprehensive treatment. Univariable and multivariable logistic regression analyses were performed to identify independent risk factors, and a nomogram was created based on the results of the multivariable analysis. The performance of the nomogram was evaluated using a receiver operating characteristic (ROC) curve, and the discriminatory capacity was assessed using the area under the curve (AUC). The model's calibration was assessed through a calibration curve and the Hosmer Lemeshow test. In the results, the multivariable logistic regression analysis revealed that age (OR: 1.23, 95% CI 1.06-3.79), HbA1c (OR: 7.168, 95% CI 1.724-25.788), perineural spread (OR: 6.3, 95% CI 1.281-19.874), and the disease stage were independent risk factors for intracranial involvement in CAM. The developed nomogram demonstrated good discriminative capacity with an AUC of 0.821 (95% CI 0.713-0.909) as indicated by the ROC curve. The calibration curve showed that the nomogram was well-calibrated, and the Hosmer Lemeshow test yielded a P-value of 0.992, indicating a good fit for the model. In conclusion, this study found that CAM particularly exhibits perineural spread, which is a predictive factor for intracranial involvement. A nomogram model incorporating age, HbA1c, disease stage, and perineural spread was successfully developed for predicting intracranial involvement in CAM patients in both in-patient and out-patient settings.

Discovery of perineural spread in COVID-19-associated mucormycosis reveals a new predictive model for intracranial complications which is crucial for early intervention.

Socioeconomic variation in the prevalence of pain by anatomical sites among middle-aged and older adults in India: a cross-sectional study.

BACKGROUND: Pain is a significant global public health concern, particularly among individuals aged 45 and above. Its impact on the overall lifestyle of the individuals varies depending on the affected anatomical parts. Despite its widespread impact, there is limited awareness of the attributes of pain, making effective pain management challenging, particularly in India. This study aims to estimate the prevalence and variation in pain in different anatomical sites among middle-aged and older adults in India. METHODS: A cross-sectional design was employed, utilising data from the first wave of the Longitudinal Aging Study in India (LASI), 2017-2018. The age-sex adjusted prevalence of pain by anatomical sites (the back, joints, and ankles) was estimated using a multivariate logistic regression model. RESULTS: 47% of individuals aged 45 years and above reported joint pain, 31% reported back pain and 20% suffered from ankle or foot pain. The prevalence of pain at all the anatomical sites increased with age and was reported higher among females. Relative to respondents aged 45-59 years, those aged 75 years and older exhibited a 41% higher likelihood of experiencing back pain (AOR: 1.41, 95% CI: 1.19-1.67), a 67% higher likelihood of joint pain (AOR: 1.67, 95% CI: 1.49-1.89), and a 32% higher likelihood of ankle/foot pain (AOR: 1.32, 95% CI: 1.16-1.50). In comparison to males, females had a 56% higher likelihood of encountering back pain (AOR: 1.56, 95% CI: 1.40-1.74), a 38% higher likelihood of joint pain (AOR: 1.38, 95% CI: 1.27-1.50), and a 35% higher likelihood of ankle/foot pain (AOR: 1.35, 95% CI: 1.17-1.57). We also found significant regional variations in pain prevalence, with higher rates in the mountainous regions of India. CONCLUSION: This research highlights the high burden of pain in major anatomical sites among middle-aged and older adults in India and emphasises the need for increased awareness and effective pain management strategies.

Comparison of depth of electrode insertion between cochleostomy and round window approach: a cadaveric study.

INTRODUCTION: Round window approach and cochleostomy approach can have different depth of electrode insertion during cochlear implantation which itself can alter the audiological outcomes in cochlear implant. OBJECTIVE: The current study was conducted to determine the difference in the depth of electrode insertion via cochleostomy and round widow approach when done serially in same temporal bone. METHODOLOGY: This is a cross-sectional study conducted in the Department of Otorhinolaryngology in conjunction with Department of Anatomy and Department of Diagnostic and Interventional Radiology over a period of 1 year. 12-electrode array insertion was performed via either approach (cochleostomy or round window) in the cadaveric temporal bone. HRCT temporal bone scan of the implanted temporal bone was done and depth of insertion and various cochlear parameters were calculated. RESULT: A total of 12 temporal bones were included for imaging analysis. The mean cochlear duct length was 32.892 mm; the alpha and beta angles were 58.175° and 8.350°, respectively. The mean angular depth of electrode insertion via round window was found to be 325.2° (SD = 150.5842) and via cochleostomy 327.350 (SD = 112.79) degree and the mean linear depth of electrode insertion via round window was found to be 18.80 (SD = 4.4962) mm via cochleostomy 19.650 (SD = 3.8087) mm, which was calculated using OTOPLAN 1.5.0 software. There was a statically significant difference in linear depth of insertion between round window and cochleostomy. Although the angular depth of insertion was higher in CS group, there was no statistically significant difference with round window type of insertion. CONCLUSION: The depth of electrode insertion is one of the parameters that influences the hearing outcome. Linear depth of electrode insertion was found to be more in case of cochleostomy compared to round window approach (p = 0.075) and difference in case of angular depth of electrode insertion existed but not significant (p = 0.529).

Structure-based virtual screening against multiple Plasmodium falciparum kinases reveals antimalarial compounds.

The continuous emergence of resistance against most frontline antimalarial drugs has led to countless deaths in malaria-endemic countries, counting 619,000 deaths in 2021, with mutation in drug targets being the sole cause. As mutation is correlated frequently with fitness cost, the likelihood of mutation emergence in multiple targets at a time is extremely low. Hence, multitargeting compounds may seem promising to address drug resistance issues with additional benefits like increased efficacy, improved safety profile, and the requirement of fewer pills compared to traditional single and combinational drugs. In this study, we attempted to use the High Throughput Virtual Screening approach to predict multitarget inhibitors against six chemically validated Plasmodium falciparum (Pf) kinases (PfPKG, PfMAP2, PfCDPK4, PfTMK, PfPK5, PfPI4K), resulting in 21 multitargeting hits. The molecular dynamic simulation of the top six complexes (Myricetin-MAP2, Quercetin-CDPK4, Myricetin-TMK, Quercetin-PKG, Salidroside-PK5, and Salidroside-PI4K) showed stable interactions. Moreover, hierarchical clustering reveals the structural divergence of the compounds from the existing antimalarials, indicating less chance of cross-resistance. Additionally, the top three hits were validated through parasite growth inhibition assays, with quercetin and myricetin exhibiting an IC50 value of 1.84 and 3.93 µM, respectively.

Exploring the association of lifestyle behaviors and healthy ageing among the older adults in India: evidence from LASI survey.

BACKGROUND: Understanding health and developing trends among the older population is essential for countries to tackle the challenges of an ageing population and formulate relevant policies. Facilitating healthy ageing is an essential strategy to address the issues arising among the aged. The concept of healthy ageing is defined as "the process of developing and maintaining the functional ability that enables wellbeing in old age (WHO)," where "functional ability comprises the health-related attributes that enable people to be and to do what they have reason to value." People have different ageing pathways depending on their genetic profile and different life course health risk exposures. Therefore, ageing, more specifically healthy ageing, largely depends on individual lifestyle choices. This study examines the association between lifestyle behaviours and healthy ageing among older adults in India. METHODS: Based on the first round of LASI in 2017-18, we conceptualized healthy ageing within the WHO functional ability framework. We developed a Healthy Ageing Index (HAI), which incorporates physiological health, functional health, cognitive functions, psychological well-being, and social engagement. We used principal component analysis to generate a composite score for HAI. We then used multiple linear regression to demonstrate the association between lifestyle behaviours and HAI. RESULT: The mean HAI was 82.8%, indicating that the study population is healthier. The study findings show that smoking and drinking are more prevalent among males, rural residents, illiterate individuals, those currently employed, and those belonging to the poorest wealth quintile. Engaging in physical activity is associated with better health outcomes (ß = 2.36; 95% CI: 2.16-2.56). CONCLUSION: This study emphasizes the importance of adopting a healthier lifestyle to achieve healthy ageing. Health behaviours are modifiable, so our results highlight the need for policy interventions to promote a healthier lifestyle from an early age.

Preoperative assessment of optic nerve sheath diameter and heart rate variability to predict intraoperative brain condition in patients with supratentorial tumors: a prospective observational study.

Brain relaxation is an important requirement in intracranial neurosurgical procedures and optimal brain relaxation improves the operating conditions. Optic nerve sheath diameter (ONSD) is a non-invasive bedside surrogate marker of intracranial pressure (ICP) status. Elevated ICP is often associated with marked autonomic dysfunction. There is no standard measure to predict intraoperative brain condition non-invasively, considering both anatomical displacement and physiological effects due to raised ICP and brain oedema. This study was aimed to determine the usefulness of heart rate variability (HRV) parameters and ONSD preoperatively in predicting intraoperative brain relaxation in patients with supratentorial tumors undergoing surgery.This prospective observational study was conducted in a tertiary care centre. 58 patients with supratentorial brain tumors undergoing elective surgery were studied. Preoperative clinical presentation, computed tomography (CT) findings, ONSD and HRV parameters were assessed in determining intraoperative brain condition. Intraoperative hemodynamic parameters and brain relaxation score after craniotomy were studied. There was significant difference in CT grade, ONSD and HRV parameters in patients between lax and tight brain. A receiver operating curve was constructed to determine the cut off to predict intraoperative brain bulge. A CT grade more than 2, ONSD of greater than 0.63 cms and ratio of low frequency to high ratio (LF/HF) of more than 1.8 were good predictors of brain bulge. The changes in ONSD and HRV parameters, with the CT findings can be used as surrogate markers of increased ICP to help predict intraoperative brain condition.

Outcomes of transcutaneous retrobulbar Amphotericin B (TRAMB) as an adjuvant therapy for rhino-orbital-cerebral mucormycosis (ROCM) following COVID-19.

PURPOSE: To assess the outcomes of transcutaneous retrobulbar Amphotericin B (TRAMB) for rhino-orbital-cerebral-mucormycosis (ROCM) post-COVID-19, as an adjuvant to standard systemic antifungal therapy. METHODS: In this prospective cohort study involving ROCM patients with clinical/radiological orbital involvement, 44 eyes with ROCM stage ≥ 3B received TRAMB for 7 consecutive days with liposomal Amphotericin-B (3.5 mg/ml) with a minimum clinical and radiological follow-up of 3 months. All patients received standard systemic antifungal therapy also as per institutional protocol. Data pertaining to demography, systemic status, clinical involvement, imaging, surgical/medical management were also recorded. Potential eyes for exenteration were excluded. Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 12 Given name: [Mahendra Kumar ] Last name [Garg]. Also, kindly confirm the details in the metadata are correct.All author names are presented accurately. Details in the metadata are correct. Thank you. RESULTS: Forty-four eyes of 42 patients were included, out of which 30 had diabetes mellitus & 22 had received steroid/oxygen treatment during COVID-19 infection. Forty eyes showed improvement or stable disease on follow-up on radiology. Four eyes which showed progression of the disease in orbit were reaugmented with TRAMB. No patient required exenteration. Subconjunctival haemorrhage occurred in six eyes and temporary blurring of vision in four eyes after TRAMB which resolved spontaneously. CONCLUSION: TRAMB, as an adjuvant to standard systemic antifungal therapy, is associated with a significant reduction or stabilisation of orbital involvement. TRAMB should be considered as an adjuvant therapy for ROCM to reduce disease progression as well as to preserve globe or sight. It has a promising role in preventing potential orbital exenterations.

In Response to Author: Hiccups before a Pulmonary Embolism Speak against This as a Cause.

How to cite this article: Goyal A, Pallavi K, Awasthy AK. In Response to Author: Hiccups before a Pulmonary Embolism Speak against This as a Cause. Indian J Crit Care Med 2023;27(3):229.

Association of pain and quality of life among middle-aged and older adults of India.

BACKGROUND: India is passing through a phase of demographic and epidemiological transition where ageing and chronic morbidities are being more common. Though studies have examined the prevalence and risk factors of pain and other chronic morbidities, nationally representative research examining the association of pain and quality of life (QoL) is limited in India. This study examines the association between pain and QoL among middle-aged and older adults in India. METHODS: This study uses the data from wave 1 of the Longitudinal Ageing Study in India (LASI) conducted in 2017-18. This study is restricted to 58,328 individuals from all states (except Sikkim), aged 45 years and above. The quality of life is measured in 6 domains (physical, psychological, social, environment, general health and life satisfaction) with 21 variables that range from 0 to 100. The principal component analysis was used to generate a composite score of QoL and the multiple linear regression was used to show the association between pain and quality of life. RESULTS: It is estimated that approximately 37% of Indian middle-aged and older populations were often troubled with pain. Pain prevalence increase with age and is more common among older adults aged 75 + years (43.37%; 95% CI, 40.95-45.80), and female (41.38%; 95% CI, 39.36-43.39). The average QoL score among those with pain was 81.6 compared to 85.2 among those without pain. QoL was lower among elderly age 75 and above, females, rural residents and illiterates. Controlling for socio-demographic factors, pain reduces the QoL by 2.57 points (ß= -2.57; 95% CI, -3.02 - -2.11). CONCLUSION: Pain reduces the quality of life among middle-aged adults and older adults in India. This evidence could potentially help the policymakers to consider pain as a significant determinant of quality of life in India.

Association of work and hypertension among middle-aged adults and elderly Indians.

PURPOSE: Over two-fifth of middle-aged adults and elderly (45 +) in India are hypertensive. Though studies examined prevalence, awareness and control of hypertension, little is known on the association of hypertension with work status in India. This study examines the variations of hypertension by types of work among middle-aged adults and the elderly in India. METHODS: Data were drawn from the Longitudinal Aging Survey of India (LASI), Wave 1, 2017-18, and analysis was restricted to participants aged 45 and above with complete information on employment and blood pressure (N = 59,196). RESULTS: We estimated the adjusted prevalence of hypertension at 49.2% (95% CI, 47.8-50.6) among the ever worked but not currently working and 44.5% (95% CI, 43.1-45.8) among currently working. Among eight broad categories of the currently working population, the adjusted estimates of hypertension were highest among legislators, senior officials and managers (71.5%; 95% CI, 41.9-101.0), followed by service and sales worker workers (44.7%; 95% CI, 41.2-48.2) and least among the professionals (37.1%; 95% CI, 27.1-47.2). Relative to never worked, legislators, senior officials and managers were twice more likely [adjusted OR (AOR) 2.00; 95% CI, 0.74-5.39] to be hypertensive, followed by plant and machine operators (AOR 1.33; 95% CI, 1.04-1.71). The odds of being hypertensive was least among those engaged in professional (engineering, health, education) activities. The other significant predictors are age, sex, residence, education level, household economic condition, family history of hypertension, chronic disease and depression. CONCLUSION: The risk of hypertension varies with the types of work in which older Indians are engaged. Awareness and treatment of hypertension in high-risk occupation are recommended.

Assessment of preoperative and postoperative cardiac function in children with adenotonsillar hypertrophy: a prospective cohort study.

PURPOSE: Chronic upper airway obstruction caused by adenotonsillar hypertrophy is one of the major cause of morbidity in children. It can lead to Obstructive Sleep Apnoea Syndrome, Pulmonary Hypertension, Cor Pulmonale and right heart failure. The study aimed to evaluate and compare various parameters of cardiac function with the help of echocardiography preoperatively and postoperatively in children undergoing adenotonsillectomy. METHODOLOGY: A prospective cohort study was conducted on 23 patients at an apex care institute, under the age group of 4-12 years, who were diagnosed with adenotonsillar hypertrophy. Preoperative symptom analysis and Echocardiographic examination were done. After the assessment, all patients underwent surgery in the form of adenotonsillectomy. Follow-up symptom analysis and echocardiographic examination was done after 3 months postoperatively. RESULTS: Significant improvement in the obstructive symptoms were noted in postoperative group as expected (p = < 0.001) and also in parameters such as mPAP (p = < 0.001), TAPSE (p = < 0.001), TAV (p = 0.001), Ejection fraction (p = 0.027) and RVMPI (p = 0.044) were improved in postoperative group. 4 patients had Grade 1 Right ventricular diastolic dysfunction, which disappeared in three patients postoperatively. CONCLUSION: We have concluded that there can be subclinical cardiac dysfunctions which occurs as a result of chronic upper airway obstruction due to untreated adenotonsillar hypertrophy. Routine cardiac screening in children presenting with sleep disordered breathing associated with adenotonsillar hypertrophy may be helpful in identifying and preventing the development of cardiopulmonary complication. These changes can be reversed by performing adenotonsillectomy.

Correlation of tumour and treatment characteristics to dose received by cochlea in volumetric arc therapy.

PURPOSE: This is a radiation field simulation study using CT images designed to see the cochlear dosimetry and its correlation with tumour and treatment characteristics during radiotherapy for head and neck cancers (HNC) for identifying the factors associated with a higher dose delivered to the cochlea. METHODS: From 2018 to 2020, 80 patients with HNC underwent volumetric arc therapy (VMAT) to a dose of 66-70 Gy at 2 Gy per fraction with bilateral cochlea contoured for VMAT optimization as an organ at risk. Minimum, mean and maximum planned radiation dose to the cochlea based on tumour and treatment characteristics and dose-volume histogram variables of VMAT plans were analysed. RESULTS: Mean (standard deviation, SD) cochlear volume was 0.14 (0.06) cm3 with maximum and mean planned doses of 10.3 (SD = 11.6) Gy and 8.5 (SD = 9.8) Gy, respectively. We found a statistically significant correlation between mean dose received by bilateral cochlea (P-0.000, rright-0.84, rleft-0.78, rmidline-0.92). Tumours of the paranasal sinuses, and the parotids and more advanced T stages were associated with a higher mean dose to cochlea but was not significant statistically. The dose received by the 95% target nodal volume (D95%) showed a significant correlation with the cochlear mean dose (P-0.000, rright-0.85, rleft-0.77, rmidline-0.93) CONCLUSION: With VMAT we have achieved a better sparing of cochlea. The mean dose to the cochlea of one side significantly differed from the other side in patients with lateralized cancers. D95% of nodal volume also showed a significant correlation with the cochlear mean dose.

Persistent Hiccups in Posterior Circulation Stroke as Rare Presentation of Pulmonary Embolism-Don't Jump the Gun.

How to cite this article: Goyal A, Pallavi K, Awasthy AK. Persistent Hiccups in Posterior Circulation Stroke as Rare Presentation of Pulmonary Embolism-Don't Jump the Gun. Indian J Crit Care Med 2022;26(9):1058-1059.

A multicentre prospective feasibility study of carbon dye tattooing of biopsied axillary node and surgical localisation in breast cancer patients.

BACKGROUND: The primary aim of this prospective, multicentre feasibility study was to determine whether the biopsied axillary node can be marked using black carbon dye and successfully identified at the time of surgery. METHODS: We included breast cancer patients undergoing needle biopsy of the axillary node. The biopsied node was tattooed at the time of needle biopsy (fine needle aspiration or core biopsy) or at a separate visit with black carbon dye (Spot® or Black Eye™). Participants underwent primary surgery or neoadjuvant chemotherapy (NACT) and axillary surgery (SNB or ALND) as per routine care. RESULTS: 110 patients were included. Median age of the women was 59 (range 31-88) years. 48 (44%) underwent SNB and 62 (56%) ALND. Median volume of dye injected was 2.0 ml (range 0.2-4.2). Tattooed node was identified intra-operatively in 90 (82%) patients. The identification rate was higher (76 of 88, 86%) in the primary surgery group compared with NACT (14 of 22, 64%) (p = 0.03). Of those undergoing NACT, the identification rate was better in the patients undergoing SNB (3 of 4, 75%) compared with ALND (11 of 18, 61%) (p > 0.99). The tattooed node was the sentinel node in 78% (28 of 36) patients in the primary surgery group and 100% (3 of 3) in the NACT group. There was no learning curve for surgeons or radiologists. The identification rate did not vary with timing between dye injection and surgery (p = 0.56), body mass index (p = 0.62) or volume of dye injected (p = 0.25). CONCLUSION: It is feasible to mark the axillary node with carbon dye and identify it intra-operatively. ClinicalTrials.gov: NCT03640819.

Applications of Adductomics in Chemically Induced Adverse Outcomes and Major Emphasis on DNA Adductomics: A Pathbreaking Tool in Biomedical Research.

Adductomics novel and emerging discipline in the toxicological research emphasizes on adducts formed by reactive chemical agents with biological molecules in living organisms. Development in analytical methods propelled the application and utility of adductomics in interdisciplinary sciences. This review endeavors to add a new dimension where comprehensive insights into diverse applications of adductomics in addressing some of society's pressing challenges are provided. Also focuses on diverse applications of adductomics include: forecasting risk of chronic diseases triggered by reactive agents and predicting carcinogenesis induced by tobacco smoking; assessing chemical agents' toxicity and supplementing genotoxicity studies; designing personalized medication and precision treatment in cancer chemotherapy; appraising environmental quality or extent of pollution using biological systems; crafting tools and techniques for diagnosis of diseases and detecting food contaminants; furnishing exposure profile of the individual to electrophiles; and assisting regulatory agencies in risk assessment of reactive chemical agents. Characterizing adducts that are present in extremely low concentrations is an exigent task and more over absence of dedicated database to identify adducts is further exacerbating the problem of adduct diagnosis. In addition, there is scope of improvement in sample preparation methods and data processing software and algorithms for accurate assessment of adducts.

Recent Advancement in Nanotechnology-Based Drug Delivery System Against Viral Infections.

In the last few decades, the exponential rise in the incidence of viral infections sets a global health emergency across the world. The biomimetic architecture, the ability to hijack host immune responses, continuous antigen shifting, and drafting are the major critical factors that are responsible for the unavailability of a concrete therapeutic regimen against viral infections. Further, inappropriate pharmacodynamic physicochemical and biological parameters such as low aqueous solubility, poor permeability, high affinity for plasm proteins, short biological half-lives, and fast elimination from the systemic circulation are the major critical factors that govern the suboptimal drug concentration at the target site that leads to the development of drug resistance. To address this issue, nanotechnology-based drug delivery approach is emerged as an altering method to attain the optimal drug concentration at the target site for a prolonged period by integrating the nanoengineering tools in the synthesis of nanoparticles. Nanodimensional configuration with enhanced permeability and retention effect, increased surface-area-to-volume ratio, provision for surface functionalization, etc., are the privileged aspects that make it an effective drug delivery system for dispensing the antiviral therapeutics. However, size, shape, charge, and surface topology of nanoparticles are the greater influential factors that determine target-specific drug delivery, optimum cellular uptake, degree of opsonization by the host immune cells, drug retention time, transcytosis, the extension of biological half-life, in vivo stability, and cytotoxicity. The review will enlighten the elaborative role of nanotechnology-based drug delivery and the major challenging aspect of clinical safety and efficacy.

Mucormycosis: A Case Series of Patients Admitted in Non-COVID-19 Intensive Care Unit of a Tertiary Care Center during the Second Wave.

Rhino-orbital-cerebral mucormycosis is an invasive fungal infection associated with mortality of 25-62%. There has been a surge in the number of cases during this second wave of coronavirus disease-2019 (COVID-19) in India. We report 10 cases of mucormycosis admitted to our adult intensive care unit. After reviewing the patient's information, we found that 60% of patients had received steroids, and most had uncontrolled blood sugar levels. Most patients received treatment with surgical debridement and antifungal, although the mortality rate was as high as 40%. We report two unique cases of renal and gastrointestinal mucormycosis as well. We concluded that poor glycemic control was the primary etiology behind the rise in the number of cases. Our report also stresses the importance of early surgical intervention and suggests further research comparing the efficacy of combination antifungal therapy versus single antifungal (amphotericin B) to help resource-limited settings in these times of drug crisis. How to cite this article: Yadav S, Sharma A, Kothari N, Bhatia PK, Goyal S, Goyal A. Mucormycosis: A Case Series of Patients Admitted in Non-COVID-19 Intensive Care Unit of a Tertiary Care Center during the Second Wave. Indian J Crit Care Med 2021;25(10):1193-1196.

A Diagnostic Stewardship Intervention To Improve Blood Culture Use among Adult Nonneutropenic Inpatients: the DISTRIBUTE Study.

Interventions to optimize blood culture (BCx) practices in adult inpatients are limited. We conducted a before-after study evaluating the impact of a diagnostic stewardship program that aimed to optimize BCx use in a medical intensive care unit (MICU) and five medicine units at a large academic center. The program included implementation of an evidence-based algorithm detailing indications for BCx use and education and feedback to providers about BCx rates and indication inappropriateness. Neutropenic patients were excluded. BCx rates from contemporary control units were obtained for comparison. The primary outcome was the change in BCxs ordered with the intervention. Secondary outcomes included proportion of inappropriate BCx, solitary BCx, and positive BCx. Balancing metrics included compliance with the Centers for Medicare and Medicaid Services (CMS) SEP-1 BCx component, 30-day readmission, and all-cause in-hospital and 30-day mortality. After the intervention, BCx rates decreased from 27.7 to 22.8 BCx/100 patient-days (PDs) in the MICU (P = 0.001) and from 10.9 to 7.7 BCx/100 PD for the 5 medicine units combined (P < 0.001). BCx rates in the control units did not decrease significantly (surgical intensive care unit [ICU], P = 0.06; surgical units, P = 0.15). The proportion of inappropriate BCxs did not significantly change with the intervention (30% in the MICU and 50% in medicine units). BCx positivity increased in the MICU (from 8% to 11%, P < 0.001). Solitary BCxs decreased by 21% in the medicine units (P < 0.001). Balancing metrics were similar before and after the intervention. BCx use can be optimized with clinician education and practice guidance without affecting sepsis quality metrics or mortality.