Comparison of intrathecal morphine versus erector spinae block for postoperative analgesia in patients with end-stage kidney disease undergoing kidney transplantation: A randomised clinical study.

Background and Aims: Intrathecal morphine (ITM) or erector spinae plane (ESP) block reduces postsurgical pain in patients who underwent kidney transplantation surgeries. We aimed to compare the effectiveness of both modalities in terms of duration and quality of postoperative analgesia along with postoperative fentanyl consumption. Methods: We conducted a randomised study and analysed 60 patients posted for elective live-related kidney transplantation surgery. They were randomised into two groups. Group M patients received ITM, whereas Group E patients received ESP block. We standardised the postoperative analgesia for both groups with intravenous fentanyl-based patient-controlled analgesia. The primary outcome was to compare the quality of analgesia using the numerical rating scale score between the groups. The secondary outcome was to observe the effect of both modalities on the duration of analgesia, postoperative fentanyl consumption, rescue analgesics requirement, catheter-related bladder discomfort and any complications. Results: We found significantly lower pain scores at rest and while coughing in Group M at all time intervals, except at 24 h while coughing. The mean time to first analgesia requirement was significantly longer in Group M than in Group E (P = 0.002). No significant difference was found in postoperative consumption of total fentanyl (P = 0.065) and rescue analgesia in both groups. In Group M, there was significantly more nausea, vomiting and pruritus (P = 0.001). Conclusions: ITM provides long-lasting postoperative analgesia at the cost of higher side effects than ESP block.

Author Response: Unanswered Questions and Contradictory Statements in the Antibiotics Prescription Guidelines.

How to cite this article: Khilnani GC, Tiwari P, Mittal S. Author Response: Unanswered Questions and Contradictory Statements in the Antibiotics Prescription Guidelines. Indian J Crit Care Med 2024;28(7):717-718.

Multifaceted role of phytoconstituents based nano drug delivery systems in combating TNBC: A paradigm shift from chemical to natural.

Triple negative breast cancer is considered to be a malignancy of grave concern with limited routes of treatment due to the absence of specific breast cancer markers and ambiguity of other potential drug targets. Poor prognosis and inadequate survival rates have prompted further research into the understanding of the molecular pathophysiology and targeting of the disease. To overcome the recurrence and resistance mechanisms of the TNBC cells, various approaches have been devised, and are being continuously evaluated to enhance their efficacy and safety. Chemo-Adjuvant therapy is one such treatment modality being employed to improve the efficiency of standard chemotherapy. Combining chemo-adjuvant therapy with other upcoming approaches of cancer therapeutics such as phytoconstituents and nanotechnology has yielded promising results in the direction of improving the prognosis of TNBC. Numerous nanoformulations have been proven to substantially enhance the specificity and cellular uptake of drugs by cancer cells, thus reducing the possibility of unintended systemic side effects within cancer patients. While phytoconstituents offer a wide variety of beneficial active constituents useful in cancer therapeutics, most favorable outcomes have been observed within the scope of polyphenols, isoquinoline alkaloids and isothiocyanates. With an enhanced understanding of the molecular mechanisms of TNBC and the advent of newer targeting technologies and novel phytochemicals of medicinal importance, a new era of cancer theranostic treatments can be explored. This review hopes to instantiate the current body of research regarding the role of certain phytoconstituents and their potential nanoformulations in targeting specific TNBC pathways for treatment and diagnostic purposes.

Profile of patients referred for lung transplant and their transplant-free survival.

INTRODUCTION: Lung transplant (LTx) is a potential treatment option for all patients with chronic, end-stage respiratory disease, who are refractory to optimal medical therapy or where no medical therapy exists. In India, LTx is still in its evolving stages and published literature is sparse. The current study was carried out to study the selection criteria for lung transplant and to evaluate the clinical and socio-economic profile of patients referred for the same at a tertiary health care facility. METHODS: The study was a descriptive, prospective, observational study. All adults referred for lung transplant were evaluated for clinical and laboratory profiles. All enrolled patients were assessed for presence of referral criteria, listing criteria, contraindications, and willingness for lung transplant. These patients were followed up for 2 years for transplant-free survival, and the Cox proportional hazards model was used to determine independent predictors of all-cause mortality. RESULTS: A total of 103 were included in study. The most common diagnosis was interstitial lung disease (57.2%), followed by bronchiectasis (17.5%) and COPD (13.6%). Most patients were referred for LTx at an advanced stage as 90% met listing criteria. Fifty-four (52.4%) patients had an absolute or relative contraindication to transplant; however, the majority of those contraindications were modifiable. Patients with a lower socio-economic status were less likely to be willing for LTx. The median survival was 757 days. A 6-minute walk distance (6MWD) lesser than 250 m was found to be an independent predictor of mortality. CONCLUSION: Making patients aware about lung transplant early in their treatment may give them sufficient time to come to terms with their disease and understand the risk and benefits associated. Efforts should be focused on screening and early treatment of reversible contraindications for the eligible patients. Patients with 6MWD < 250 m are at increased risk of mortality.

Utility and safety of endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC): A systematic review and meta-analysis.

BACKGROUND: Modalities to improve tissue acquisition during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have been investigated. Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC) is a modality to obtain larger histological samples by inserting a cryoprobe into the mediastinal lesion. We aimed to study the diagnostic yield and safety of EBUS-TMC. METHODS: We performed a systematic search of the PubMed and Embase databases to extract the relevant studies. We then performed a meta-analysis to calculate the diagnostic yield of EBUS-TMC and compare it with EBUS-TBNA. RESULTS: Following a systematic search, we identified 14 relevant studies (869 patients undergoing EBUS-TMC and EBUS-TBNA). We then performed a meta-analysis of the diagnostic yield of EBUS-TMC and EBUS-TBNA from studies wherein both procedures were performed. The pooled diagnostic yield of EBUS-TMC was 92% (95% confidence interval [CI], 89%-95%). The pooled diagnostic yield of EBUS-TBNA was 81% (95% CI, 77%-85%). The risk difference in yield was 11% (95% CI, 6%-15%, I2 = 0%) when EBUS-TMC and EBUS-TBNA were compared. The only complication reported commonly with EBUS-TMC was minor bleeding. The complication rate was comparable with EBUS-TBNA. CONCLUSION: EBUS-TMC provides a greater diagnostic yield with a similar risk of adverse events compared to EBUS-TBNA. Future studies are required to clearly establish which patients are most likely to benefit from this modality.

Rituximab for rheumatoid arthritis-related interstitial lung disease: A systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis aimed at summarizing the evidence of efficacy and safety of rituximab in rheumatoid arthritis-related interstitial lung disease (RA-ILD). Materials and methods: PubMed and Embase databases were searched until June 22, 2022, to identify studies on RA-ILD treated with rituximab, confined to predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies to assess the overall stabilization or improvement in ILD, changes in percent-predicted (%-predicted) forced vital capacity (FVC), and %-predicted diffusion capacity of lungs for carbon monoxide (DLCO) following rituximab therapy. Results: A total of 15 studies (4 prospective and 11 retrospective studies) were included, with a total of 314 patients. There were 105 (60.7%) females out of 173 subjects for whom sex details were available from seven studies. The overall pooled proportion of patients with stabilization or improvement in ILD was 0.88 [95% confidence interval (CI): 0.76-0.96, p=0.02]. Rituximab improved FVC from baseline by 7.50% (95% CI: 1.35-13.65; p=0.02, fixed effect). Similarly, rituximab improved DLCO by 6.39% (95% CI: 1.366-14.43; p=0.12, random-effect). Two retrospective studies reported reduced mortality with rituximab therapy compared to tumor necrosis factor-alpha inhibitors. Conclusion: Treatment with rituximab in RA-ILD was associated with a significant improvement in %-predicted FVC, as well as stabilization or improvement in ILD after one year of treatment.

A multicentre, double-blind, placebo-controlled randomized trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-2).

BACKGROUND: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. MATERIALS AND METHODS: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. RESULTS: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. CONCLUSION: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846].

Antioxidant therapies for obstructive sleep apnea: A systematic review and meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) is a common clinical problem that is associated with adverse cardiovascular outcomes attributed to the oxidative stress due to sympathetic overstimulation. Treatment approaches targeting oxidative stress have been tried by multiple investigators. This systematic review and meta-analysis evaluated the efficacy and safety of such approaches. METHODS: Pubmed and Embase databases were searched for human studies evaluating the utility of antioxidant therapies in patients with OSA. RESULTS: A total of six studies (five randomized trials and one case-control study) were included, including 160 patients with OSA using N-acetyl cysteine, vitamin C, carbocysteine, superoxide dismutase, vitamin E, allopurinol, and their combinations. There was a significant improvement in flow-mediated dilatation (FMD) following antioxidants, with the pooled effect being 2.16 % (95% CI 1.65-2.67) using the random-effects model (I2 = 0% and p<0.001). It was also associated with a significant reduction in malondialdehyde levels and an increase in reduced glutathione (GSH) levels. There was also a significant improvement in the Epworth sleepiness scale, oxygen desaturation index, and minimum oxygen saturation during sleep without any significant adverse effects. CONCLUSION: Antioxidant therapy in patients with OSA is associated with improved endothelial function, reduced oxidative stress, and improved sleep parameters. These results call for future multicentre studies with longer follow-ups to assess the utility of antioxidant therapy in patients with OSA.

Association of Leukocyte Subpopulations Identified by Flow Cytometry with Outcomes of Sepsis in a Respiratory Intensive Care Unit: An Observational Study.

INTRODUCTION: The dysregulated host immune response in sepsis is orchestrated by peripheral blood leukocytes. This study explored the associations of the peripheral blood leukocyte subpopulations with early clinical deterioration and mortality in sepsis. METHODS: We performed a prospective observational single-center study enrolling adult subjects with sepsis within 48 h of hospital admission. Peripheral blood flow cytometry was performed for the patients at enrolment and after 5 days. The primary outcome was to explore the association between various leukocyte subpopulations at enrolment and early clinical deterioration [defined as an increase in the sequential organ failure assessment (SOFA) score between enrolment and day 5, or death before day 5]. Other pre-specified outcomes explored associations of leukocyte subpopulations at enrolment and on day 5 with in-hospital mortality. RESULTS: A total of 100 patients, including 47 with septic shock were enrolled. The mean (SD) age of the patients was 53.99 (14.93) years. Among them, 26 patients had early clinical deterioration, whereas 41 died during hospitalization. There was no significant association between the leukocyte subpopulations at enrolment and early clinical deterioration on day 5. On multivariate logistic regression, a reduced percentage of CD8 + CD25+ T-cells at enrolment was associated with in-hospital mortality [odds ratio (OR), 0.82 (0.70-0.97); p-value = 0.02]. A reduced lymphocyte percentage on day 5 was associated with in-hospital mortality [OR, 0.28 (0.11-0.69); p-value = 0.01]. In a post-hoc analysis, patients with "very early" deterioration within 48 h had an increased granulocyte CD64 median fluorescent intensity (MFI) [OR, 1.07 (1.01-1.14); p-value = 0.02] and a reduced granulocyte CD16 MFI [OR, 0.97 (0.95-1.00); p-value = 0.04] at enrolment. CONCLUSIONS: None of the leukocyte subpopulations showed an association with early clinical deterioration at day 5. Impaired lymphocyte activation and lymphocytopenia indicative of adaptive immune dysfunction may be associated with in-hospital mortality.

Enhancement of Curcumin's Anti-Psoriatic Efficacy via Formulation into Tea Tree Oil-Based Emulgel.

Psoriasis is a chronic inflammatory skin disease characterized by the hyperproliferation and aberrant differentiation of epidermal keratinocytes. It is a debilitating condition that can cause significant physical and emotional distress. Natural anti-psoriatic agents have been investigated as alternatives to conventional allopathic medications, as they have notable limitations and drawbacks. Curcumin and tea tree oil are cost-efficient and effective anti-inflammatory medicines with less adverse effects compared to synthetic psoriasis medications. Our research endeavors to harness the therapeutic potential of these natural compounds by developing an herbal anti-psoriatic topical drug delivery system. This novel method uses curcumin and tea tree oil to create a bi-phasic emulgel drug delivery system. Formulations F1 (gel) and F2 (emulgel) have high drug content percentages of 84.2% and 96.7%, respectively. The emulgel showed better spreadability for cutaneous applications, with a viscosity of 92,200 ± 943 cp compared to the gel's 56,200 ± 1725 cp. The emulgel released 94.48% of the drugs, compared to 87.58% for the gel. These formulations conform to the zero-order and Higuchi models, and their stability over a three-month period is crucial. In vivo, the emulgel healed psoriasis symptoms faster than the usual gel. The gathered results confirmed the emulgel's potential as a drug delivery method, emphasizing the complementary benefits of tea tree oil and curcumin as an effective new therapy for psoriasis.

An overview of unresolved issues in the perioperative management of liver transplant patients.

Over the past decade, the field of solid organ transplantation has undergone significant changes, with some of the most notable advancements occurring in liver transplantation. Recent years have seen substantial progress in preoperative patient optimization protocols, anesthesia monitoring, coagulation management, and fluid management, among other areas. These improvements have led to excellent perioperative outcomes for all surgical patients, including those undergoing liver transplantation. In the last few decades, there have been numerous publications in the field of liver transplantation, but controversies related to perioperative management of liver transplant recipients persist. In this review article, we address the unresolved issues surrounding the anesthetic management of patients scheduled for liver transplantation.

Prevalence of chronic obstructive pulmonary disease in Indian nonsmokers: a systematic review & meta-analysis.

INTRODUCTION: Nonsmokers with chronic obstructive pulmonary disease (COPD) are neglected despite constituting half of all cases in studies from the developed world. Herein, we systematically reviewed the prevalence of COPD among nonsmokers in India. CONTENT: We searched Embase, Scopus, and PubMed databases for studies examining the prevalence of COPD among nonsmokers in India. We used the Joanna Briggs Institute (JBI) checklist to assess included studies' quality. Meta-analysis was performed using random-effects model. SUMMARY: Seven studies comprising 6,903 subjects were included. The quality of the studies ranged from 5/9 to 8/9. The prevalence of COPD varied between 1.6 and 26.6 %. Studies differed considerably in demographics and biomass exposure profiles of subjects. Among the four studies that enrolled both middle-aged and elderly Indian nonsmokers not screened based on biomass fuel exposure, the pooled prevalence of COPD was 3 % (95 % CI, 2-3 %; I2=50.52 %, p=0.11). The pooled prevalence of COPD among biomass fuel-exposed individuals was 10 % (95 % CI, 2-18 %; I2=98.8 %, p<0.001). OUTLOOK: Limited evidence suggests a sizable burden of COPD among nonsmokers and biomass fuel-exposed individuals in India. More epidemiological studies of COPD in nonsmokers are needed from low and middle-income countries.

Transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA) for left adrenal gland (LAG) sampling: A report of three cases with a review of the literature.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard-of-care modality for evaluating mediastinal lymph nodes and masses. The EBUS bronchoscope may also be introduced through the oesophageal route to perform sampling of accessible lesions, a technique described as transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA). Because of the central oesophageal approach, EUS-B-FNA provides easy access to the left para-tracheal, subcarinal and para-oesophageal lymph nodes. In addition, the left adrenal gland (LAG) can also be imaged and sampled during the EUS-B-FNA procedure. In patients with suspected lung cancer, accurate staging is essential. Adrenal metastasis is relatively common and may often be a solitary metastatic site. We describe three cases where EUS-B-FNA was performed to safely sample the enlarged LAG in suspected lung cancer. We also review the literature on the performance characteristics of EUS-B-FNA for LAG aspiration.

Perioperative management of a severely thrombocytopenic kidney transplant recipient using thromboelastography.

Perioperative transfusion of blood and blood products can be avoided or reduced with bedside real time monitoring of coagulation in patients at risk. Thromboelastography (TEG), is a point of care coagulation monitor to assess dynamic progress of clot formation. We report a case of 26 years old female patient with end-stage kidney disease (ESKD) who underwent living donor kidney transplantation at our institute. On preoperative work-up, her complete blood count revealed severe thrombocytopenia. Etiology of thrombocytopenia could not be established except past history of hemolysis, elevated liver enzymes, and low platelets syndrome in her last pregnancy. Perioperative transfusion of blood and blood products was guided with TEG and transplant was conducted successfully without any transfusion. In conclusion, severe thrombocytopenia in patients with ESKD enhances the risk of perioperative bleeding and related complications in already compromised coagulation system. Kidney transplant without pre-emptive transfusion could be possible with perioperative use of TEG.

Basic spirometry and advanced pulmonary function tests - NATCON 2022.

At the 77th National Conference on Tuberculosis and Chest Diseases, which took place on February 27, 2023, a pre-conference workshop on Basic Spirometry and Advanced Pulmonary Function Tests was held under the auspices of NATCON-2022. With the assistance of highly experienced faculty who are national and international level experts in their fields, the workshop covered all important aspects of basic spirometry and advanced Pulmonary Function Tests.

Quality by design engineered, enhanced anticancer activity of temozolomide and resveratrol coloaded NLC and brain targeting via lactoferrin conjugation in treatment of glioblastoma.

The most dangerous type of high-grade astrocytoma is glioblastoma multiforme. The objective of the work was to engineer lactoferrin conjugated temozolomide and resveratrol co-loaded NLC for the treatment of glioblastoma using intranasal delivery for brain targeting. Synergistic activity of temozolomide and resveratrol was determined using combination index method and 1:1 ratio was selected. QbD approach was used to formulate and optimize NLC, with minimum particle size, maximum transmittance and entrapment efficiency using Central Composite Rotable Design (CCRD) method. The optimized LTR-NLC had desired average particle size (209.3 nm), narrow PDI along, high percentage transmittance (>95%) and better entrapment efficiency (95.26% of TEM and 87.59% of RES). From ex-vivo permeation studies it was found that the permeation at 24 h was 77.43 %, and 88.55 % from LTR-NLC and 25.76 % and 31.10% from suspension for resveratrol and temozolomide respectively. In comparison to drug suspension, NLC had nearly 3-fold increase in drug penetration. IC50 value was also significantly better in the groups treated with LTR-NLC. Hence it can be concluded that LTR-NLC may be an effective formulation for the treatment of glioblastoma, according to the findings of this investigation.

Systematic review and meta-analysis of the prevalence of obstructive sleep apnea in Indian adults.

Obstructive sleep apnea (OSA) is a common sleep disorder associated with considerable morbidity. However, there is an underrepresentation of data from India and other developing countries in global reviews of OSA prevalence. This systematic review and meta-analysis examined the prevalence of OSA in India. The MEDLINE, Embase, and Scopus databases were searched for articles that reported the prevalence of OSA in the general Indian adult population using sleep studies. Eight studies were included comprising 11,009 subjects with mean age ranging from 35.5 to 47.8 years. On the Joanna Briggs Institute (JBI) checklist for prevalence studies, the study quality ranged from 3/9 to 9/9. Meta-analysis was performed using the random-effects model. The pooled prevalence of OSA (AHI ≥5 events/hour) was 11% overall (95% CI: 7%-15%; I2 = 98.0%, p<0.001), 13% in males (95% CI: 7%-18%; I2 = 96.0%, p<0.001), and 5% in females (95% CI: 3%-7%; I2 = 73.3%, p = 0.01). The pooled prevalence of moderate-to-severe OSA (AHI ≥15 events/hour) was 5% (95% CI: 2%-8%, I2 = 95.3%; p = 0.01). Based on these findings, approximately 104 million Indians of working age suffer from OSA, of whom 47 million have moderate-to-severe OSA. This represents a major public health problem in India with important implications for the global burden of the disease.

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.