A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Effect of Topical Urea for Secondary Prophylaxis of Hand Foot Skin Reaction in Renal Cell Cancer Patients on Sunitinib Therapy.

INTRODUCTION: Hand foot skin reaction (HFSR) is a common dose-limiting adverse effect of multi kinase inhibitors (MKI) whose mechanism is not fully understood, and the prophylaxis is inadequate. OBJECTIVE: In this pilot study, a double-blind, randomized placebo-controlled trial was conducted to evaluate the effect of topical urea in secondary prevention of sunitinib-induced HFSR in renal cell cancer patients. METHODS: Out of 55 screened patients, 14 were randomized to receive topical urea or placebo for four weeks. The association of HFSR with drug levels of sunitinib and its metabolite (n-desethyl sunitinib), genetic polymorphism of VEGFR2 gene, quality of life (QOL) and biochemical markers was also assessed. RESULTS: The results showed that urea-based cream was not superior to placebo (P = .075). There was no change in the QOL in both the groups. Single nucleotide polymorphism was checked for two nucleotides rs1870377 and rs2305948 located in VEGFR2 gene on chromosome 4. SNP (variant T > A) at rs1870377 was associated with appearance of new HFSR as compared to the wild type, although the association was not statistically significant (OR 0.714). There was no statistically significant difference between mean plasma levels of sunitinib and N-desethyl sunitinib in urea arm as compared to placebo arm as compared to placebo. The best fit population pharmacokinetic model for sunitinib was one compartment model with first order absorption and linear elimination. The median (IQR) of population parameters calculated from the population pharmacokinetics model for Ka, V and Cl was 0.22 (0.21-0.24) h-1, 4.4 (4.09-4.47) L, 0.049 (0.042-0.12) L/hr, respectively. CONCLUSION: The study suggested that the urea-based cream was not superior to placebo in decreasing the appearance of new HFSR in renal cancer patients receiving 4:2 regimen of sunitinib.

Nocardia otitidiscaviarum causing pulmonary nocardiosis: a case report and its review of the literature.

Background: Infections caused by Nocardia spp. can occur in immunocompromised as well as immunocompetent individuals. Although nocardiosis is rare, it is being increasingly recognized owing to the rise in occurrence rate over the years. The documentation of pleural involvement in nocardiosis is rare in India. Case: We report a case of pulmonary nocardiosis in an immunocompromised individual caused by Nocardia otitidiscaviarum. Discussion: Pulmonary nocardiosis caused by Nocardia otitidiscaviarum may go unnoticed without clinical suspicion. Correct and timely identification is the key to proper patient management. Conclusion: Coordination between clinicians and microbiologists is necessary for early diagnosis and appropriate management of nocardiosis.

Attitude of Indian nurses towards importance of families in nursing care: A cross-sectional study.

AIMS AND OBJECTIVE: To evaluate the attitudes of Indian nurses towards the importance of family involvement in nursing care and the association between nurse attitudes and sociodemographic characteristics. BACKGROUND: Involving the family in the care process is crucial for delivering family- and patient-centred care and ensuring the best possible patient outcomes. Nevertheless, published literature revealed that the nurses may lack clarity regarding the role of family members in the patient's care, which in turn hinders families' participation in care. DESIGN: Cross-sectional descriptive study. The STROBE checklist was used to report the present study. METHODS: A total of 203 Nurses participated in a prospective cross-sectional study between May 2022 and August 2022. They were recruited through convenience sampling from two tertiary care centres in India. A two-part questionnaire was used to gather the data; the first section contained questions for gathering sociodemographic information, and the second part contained the standardized FINC-NA scale. RESULTS: The mean age of the nurses was (28.08 ± 4.722) years, and their median professional experience was 2.5 (1-5.5) years. Nurses' attitude regarding family's importance in patient care was found to be significantly associated (p ≤ .05) with education level, marital status, religion and hometown region. CONCLUSION: In several items Indian nurses have positive attitudes towards family involvement in care but some of the lower scoring items can present opportunities for focused improvement. Continuing development programmes about family-centered care can constitute important strategies to improve the positive attitudes of nurses towards families in practice. PATIENT AND PUBLIC CONTRIBUTION: No patient or public contribution.

Acquired resistance to KRAS G12C small-molecule inhibitors via genetic/nongenetic mechanisms in lung cancer.

Inherent or acquired resistance to sotorasib poses a substantialt challenge for NSCLC treatment. Here, we demonstrate that acquired resistance to sotorasib in isogenic cells correlated with increased expression of integrin ß4 (ITGB4), a component of the focal adhesion complex. Silencing ITGB4 in tolerant cells improved sotorasib sensitivity, while overexpressing ITGB4 enhanced tolerance to sotorasib by supporting AKT-mTOR bypass signaling. Chronic treatment with sotorasib induced WNT expression and activated the WNT/ß-catenin signaling pathway. Thus, silencing both ITGB4 and ß-catenin significantly improved sotorasib sensitivity in tolerant, acquired, and inherently resistant cells. In addition, the proteasome inhibitor carfilzomib (CFZ) exhibited synergism with sotorasib by down-regulating ITGB4 and ß-catenin expression. Furthermore, adagrasib phenocopies the combination effect of sotorasib and CFZ by suppressing KRAS activity and inhibiting cell cycle progression in inherently resistant cells. Overall, our findings unveil previously unrecognized nongenetic mechanisms underlying resistance to sotorasib and propose a promising treatment strategy to overcome resistance.

Developing Standard Treatment Workflows-way to universal healthcare in India.

Primary healthcare caters to nearly 70% of the population in India and provides treatment for approximately 80-90% of common conditions. To achieve universal health coverage (UHC), the Indian healthcare system is gearing up by initiating several schemes such as National Health Protection Scheme, Ayushman Bharat, Nutrition Supplementation Schemes, and Inderdhanush Schemes. The healthcare delivery system is facing challenges such as irrational use of medicines, over- and under-diagnosis, high out-of-pocket expenditure, lack of targeted attention to preventive and promotive health services, and poor referral mechanisms. Healthcare providers are unable to keep pace with the volume of growing new scientific evidence and rising healthcare costs as the literature is not published at the same pace. In addition, there is a lack of common standard treatment guidelines, workflows, and reference manuals from the Government of India. Indian Council of Medical Research in collaboration with the National Health Authority, Govt. of India, and the WHO India country office has developed Standard Treatment Workflows (STWs) with the objective to be utilized at various levels of healthcare starting from primary to tertiary level care. A systematic approach was adopted to formulate the STWs. An advisory committee was constituted for planning and oversight of the process. Specialty experts' group for each specialty comprised of clinicians working at government and private medical colleges and hospitals. The expert groups prioritized the topics through extensive literature searches and meeting with different stakeholders. Then, the contents of each STW were finalized in the form of single-pager infographics. These STWs were further reviewed by an editorial committee before publication. Presently, 125 STWs pertaining to 23 specialties have been developed. It needs to be ensured that STWs are implemented effectively at all levels and ensure quality healthcare at an affordable cost as part of UHC.

Targeting ITGB4/SOX2-driven lung cancer stem cells using proteasome inhibitors.

This study investigates the role of integrin ß4 (ITGB4) and stemness-associated factor SOX2 in platinum resistance in lung squamous cell carcinoma (LUSC). The expression of SOX2 and ITGB4 is found to be high in all LUSC subtypes, but the impact of ITGB4 expression on overall patient survival varies by subtype. Cancer stem cells (CSCs) isolated from LUSC patients were found to be resistant to cisplatin, but knocking down ITGB4 or SOX2 sensitized them to cisplatin. Carfilzomib (CFZ) synergized with cisplatin and suppressed CSC growth by inhibiting ITGB4 and SOX2 expression. Additionally, CFZ was found to inhibit SOX2 expression epigenetically by inhibiting histone acetylation at the SOX2 promoter site. CFZ also suppressed the growth of SOX2-dependent small cell lung cancer cells in vitro and in vivo. The study highlights the unique function of CFZ as a transcriptional suppressor of SOX2, independent of its proteasome inhibitory function.

Giardiasis in an Infant With Fibrosarcoma: A Case Report.

INTRODUCTION: Giardia lamblia is a neglected parasitic infection that typically affects the developing nations of the world. It is a microscopic intestinal parasite that is known to cause stomach cramps, bloating, nausea and bouts of diarrhoea. CASE PRESENTATION: Here, we are presenting the case of a 1.5 years-old-baby with an immunocompromised condition who got infected by Giardia lamblia. The baby with fibrosarcoma was receiving treatment in our tertiary care centre, and later developed abdominal and minor systemic complaints. Stool samples were collected, which showed trophozoites and cysts of Giardia. DISCUSSION: To the best of our knowledge, this is the first case of Giardia lamblia infection in a paediatric patient with fibrosarcoma. The patient improved after taking metronidazole for ten days. CONCLUSION: It is critical to keep a watch out for this neglected parasite, and suggested samples, particularly stool samples, must be sent for investigation in order to diagnose and manage these cases properly.

Cryptosporidiosis in India and the World: A Review.

Cryptosporidiosis is caused by infection with a coccidian parasite belonging to the genus Cryptosporidium. Initially, human cryptosporidiosis was believed to be caused only by one species, but since the advent of molecular studies, 15 more species have been discovered to cause this infection. Among them, Cryptosporidium hominis and Cryptosporidium parvum are the most common species involved. This mainly affects children and causes diarrhea in most cases. It is mainly diagnosed by microscopy, especially in low-middle-income countries. This review covers the epidemiology, life cycle, risk factors, clinical manifestations, different diagnostic methods and treatment of this disease.

Detection of Antibodies against Toxoplasma from Human Serum Sample using ELISA.

BACKGROUND: Toxoplasmosis is a common worldwide zoonotic infection affecting warm blooded animals and humans caused by Toxoplasma gondii. Clinical features range from mildfebrile illness and lymphadenopathy in the immunocompetent host to encephalitisin the immunosuppressed host (E.g. HIV infected patients). Congenital infection can also occur. For effective control and treatment of toxoplasmosis, accurate detection of T. gondii infection is important. OBJECTIVE: In this study, ELISA detecting anti-toxoplasma antibodies IgM and IgG has been used for diagnosing Toxoplasmosis in patients. METHODS: Enzyme-linked immunosorbentassay (ELISA) was carried out in serum samples collected from 40 patients to detect anti-toxoplasma IgG and IgM antibodies as a part of work up in suspected cases. Relevant clinical history was also taken. RESULTS: Of the total 40 samples taken, only one sample came positive for IgM and 9 came positive for IgG antibody. All patients who were seropositivefor T. gondii antibodies had HIV infection. Five patients were in the age group between 30 to 40 years. CONCLUSION: From the limited data available in this study, it may be recommended to screen for T. gondii antibodies in HIV patients.

Cryptosporidiosis in Yellow Nail Syndrome - A Rare Case Report.

BACKGROUND: Cryptosporidium species infection causes malabsorption and severe diarrhea in immunocompromised hosts. Association of Yellow Nail Syndrome (YNS) and Cryptosporidiosis is rare and has not been reported till date. Immunity can also be affected in this case of YNS is associated with autoimmune disorders. CASE PRESENTATION: Here, we describe a case of persistent diarrhea in an 8 month old YNS patient. Modified Ziehl-Neelsen staining and Saffranine-Methylene blue revealed oocyts of Cryptosporidium species. Following appropriate treatment, the patient's symptoms improved and the patient was discharged in a hemodynamically stable condition. DISCUSSION: Cryptosporidiosis is a significant cause of morbidity and mortality in immunocompromised patients. YNS per se as well as treatment including steroids leads to immunosuppression in individuals making them susceptible host for opportunistic infections like Cryptosporidiosis. CONCLUSION: Clinicians should be aware of the condition and screen for Cryptosporidiosis in any immunocompromised patients with diarrheal symptoms, as parasitic infection like this are opportunistic in them.

Chemokines and NSCLC: Emerging role in prognosis, heterogeneity, and therapeutics.

Lung cancer persists to contribute to one-quarter of cancer-associated deaths. Among the different histologies, non-small cell lung cancer (NSCLC) alone accounts for 85% of the cases. The development of therapies involving immune checkpoint inhibitors and angiogenesis inhibitors has increased patients' survival probability and reduced mortality rates. Developing targeted therapies against essential genetic alterations also translates to better treatment strategies. But the benefits still seem farfetched due to the development of drug resistance and refractory tumors. In this review, we have highlighted the interplay of different tumor microenvironment components, essentially discussing the chemokine families (CC, CXC, C, and CX3C) that regulate the tumor biology in NSCLC and promote tumor growth, metastasis, and associated heterogeneity. The development of therapeutics and prognostic markers is a complex and multipronged approach. However, some essential chemokines can act as critical players for being considered potential prognostic markers and therapeutic targets.

Wound Infiltration and Instillation Technique for Postoperative Analgesia Using Bupivacaine in Patients Undergoing Lumbar Spine Surgeries.

BACKGROUND: Pain relief after surgery continues to be a major medical challenge in clinical practice. Lumbar spine surgery is associated with significant postoperative pain. Providing optimal analgesia locally in the area of surgical wound, with little systemic side-effects, is a favourable option and has become an intrinsic part of multimodal analgesia. We aimed to assess and compare the effectiveness of local infiltration and instillation of bupivacaine for postoperative analgesia in patients undergoing lumbar spine surgery. MATERIALS AND METHODS: Forty-four adult patients of the American Society of Anesthesiologists (ASA) class I and II were randomly assigned into two groups, incorporating 22 patients per group. After the completion of lumbar spine surgery and after hemostasis was achieved, patients in group A received instillation of 20 ml of 0.25% bupivacaine at the surgical wound site and patients in group B received 20 ml of 0.25% bupivacaine infiltration into the paravertebral muscles on either side. Postoperative numerical rating scale (NRS) pain scores at 1, 2, 3, 4, 5, 6, 7, 8, 14, 20, and 24 hours; the time to first analgesic required, total rescue analgesic consumption, and adverse effects were recorded. Statistical analysis was done using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp, Armonk, New York, United States). RESULTS: Time to the first analgesic requirement was significantly longer in group A (12.39±1.56 hours) compared to the B group (2.48±0.58 hours) (P < 0.001). The amount of rescue analgesia (diclofenac sodium) required was significantly higher in group B (135.00±46.17 milligrams) compared to A (93.75±33.32 milligrams) (P = 0.001). The number of analgesic demands was higher in the infiltration group compared to the instillation group and was observed to be statistically significant. Hemodynamic parameters remained comparable between the groups. CONCLUSION: Local instillation of surgical wound site provided better pain control than infiltration technique and is effective and safe postoperative analgesia in patients undergoing laminectomy surgeries.

Severity, Risk Factors and Quality of Life of Patients associated with Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) refers to numbness, tingling, and burning sensation caused by chemotherapy that can cause impairment in Quality of Life (QoL) of the patients. Study assesses severity, risk factors, and quality of life of patients associated with CIPN. A cross sectional descriptive study was conducted at day care ward, tertiary care hospital India. Total of 98 patients receiving paclitaxel for ≥4 months were enrolled by convenient sampling. Data regarding demographics and clinical characteristics, CIPN severity, risk factors, and QoL were collected by structured questionnaires. Study revealed that median score of autonomic symptoms was higher than sensory and motor symptoms. Mean score of FACT/GOG-Ntx sub-domain was 99.05 ± 20.87on a scale of 0 to 152. ECOG Performance status, current exercise behavior, and fruit and vegetable intake was found to be significantly (at p < .05) associated with sensory, motor, and autonomic symptom score. Therefore, CIPN was found to have debilitating effect on QoL.

A Case of Toxoplasma gondii and Strongyloides stercoralis Coinfection in an Immunocompromised Patient.

BACKGROUND: In India, around 23.49 lac people have HIV/AIDS (PLHA). Strongyloidiasis and toxoplasmosis are some of the opportunistic infections that occur in HIV patients, but their dual coinfection with HIV is rarely reported. CASE PRESENTATION: A 46-year-old male was admitted to the hospital with generalized weakness, loss of weight, and bleeding per rectum for the last 3 months and a few episodes of dizziness and fever. RESULTS: On routine investigation, he was diagnosed with human immunodeficiency virus (HIV) infection. On further evaluation, Toxoplasma gondii and Strongyloides stercoralis coinfection, as assessed by the parasitological diagnosis of the serum sample, was positive. Patient was started on artesunate, ART regimen (Tab, TLD- Dolutegravir 50 + Lamivudine 300 + Tenofovir DF 300) and cotrimoxazole. CONCLUSION: Herein, we report a case of Toxoplasma gondii and Strongyloides stercoralis coinfection in an immunocompromised patient.

WITHDRAWN: Pulmonary Nocardiosis Caused by Nocardia otitidiscaviarum in an Immunocompromised Patient and Its Review of Literature

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Molecular mechanisms of action of epigallocatechin gallate in cancer: Recent trends and advancement.

Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is an ester of epigallocatechin and gallic acid. EGCG, abundantly found in tea, is a polyphenolic flavonoid that has the potential to affect human health and disease. EGCG interacts with various recognized cellular targets and inhibits cancer cell proliferation by inducing apoptosis and cell cycle arrest. In addition, scientific evidence has illustrated the promising role of EGCG in inhibiting tumor cell metastasis and angiogenesis. It has also been found that EGCG may reverse drug resistance of cancer cells and could be a promising candidate for synergism studies. The prospective importance of EGCG in cancer treatment is owed to its natural origin, safety, and low cost which presents it as an attractive target for further development of novel cancer therapeutics. A major challenge with EGCG is its low bioavailability which is being targeted for improvement by encapsulating EGCG in nano-sized vehicles for further delivery. However, there are major limitations of the studies on EGCG, including study design, experimental bias, and inconsistent results and reproducibility among different study cohorts. Additionally, it is important to identify specific EGCG pharmacological targets in the tumor-specific signaling pathways for development of novel combined therapeutic treatments with EGCG. The present review highlights the ongoing development to identify cellular and molecular targets of EGCG in cancer. Furthermore, the role of nanotechnology-mediated EGCG combinations and delivery systems will also be discussed.

Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer.

Protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of apoptosis, proliferation, and DNA-damage response, is overexpressed in many cancers, including small cell lung cancer (SCLC). Here we report that LB100, a small molecule inhibitor of PP2A, when combined with platinum-based chemotherapy, synergistically elicited an antitumor response both in vitro and in vivo with no apparent toxicity. Using inductively coupled plasma mass spectrometry, we determined quantitatively that sensitization via LB100 was mediated by increased uptake of carboplatin in SCLC cells. Treatment with LB100 alone or in combination resulted in inhibition of cell viability in two-dimensional culture and three-dimensional spheroid models of SCLC, reduced glucose uptake, and attenuated mitochondrial and glycolytic ATP production. Combining LB100 with atezolizumab increased the capacity of T cells to infiltrate and kill tumor spheroids, and combining LB100 with carboplatin caused hyperphosphorylation of the DNA repair marker γH2AX and enhanced apoptosis while attenuating MET signaling and invasion through an endothelial cell monolayer. Taken together, these data highlight the translational potential of inhibiting PP2A with LB100 in combination with platinum-based chemotherapy and immunotherapy in SCLC.

COVID-19 seropositivity among non-medical frontline office staff from two cities in Rajasthan, India.

AIMS: The indigenously developed Indian Council of Medical Research (ICMR)-NIV COVID Kavach IgG enzyme linked immunosorbent assay (ELISA) has been recommended for seroprevalence among vulnerable populations in India, which provided essential services throughout the lockdown. The staff working in the High Court was one such group. We compared anti-SARS-CoV-2 IgG seropositivity among the staff of Jodhpur and Jaipur High Courts, Rajasthan, India. METHODS: Asymptomatic judiciary staff of Jodhpur and Jaipur benches of High Courts were enrolled after informed written consent. A questionnaire was filled and 3-5 ml venous blood was collected from participants. The ICMR-NIV COVID Kavach IgG ELISA and EUROIMMUN IgG ELISA were used for detection of Anti-SARS-CoV-2 IgG antibodies. RESULTS: A total of 63 samples (41 from Jodhpur and 22 from Jaipur) were collected between 28th July to 4th August 2020. The overall anti-SARS-CoV-2 IgG seroprevalence was found to be 6.35%. Seropositivity was higher among the staff from Jaipur (13.64%) as compared to Jodhpur (2.44%). The Kavach ELISA results were in complete agreement with EUROIMMUN ELISA. The infection control measures were deemed effective. CONCLUSION: Seroprevalence among the staff of Jodhpur High Court was found to be lower than Jaipur, reflecting higher susceptibility to COVID-19 in the former. Many offices worldwide are closed till mid 2020 but need to come up with pre-emptive policies eventually. This study may help to anticipate the possible challenges when other government/private offices start functioning. The infection control practices of one workplace may help formulate guidelines for other offices.

Targeting the mercapturic acid pathway for the treatment of melanoma.

The treatment of metastatic melanoma is greatly hampered by the simultaneous dysregulation of several major signaling pathways that suppress apoptosis and promote its growth and invasion. The global resistance of melanomas to therapeutics is also supported by a highly active mercapturic acid pathway (MAP), which is responsible for the metabolism and excretion of numerous chemotherapy agents. The relative importance of the MAP in melanoma survival was not recognized until demonstrated that B16 melanoma undergoes dramatic apoptosis and regression upon the depletion or inhibition of the MAP transporter protein RLIP. RLIP is a multi-functional protein that couples ATP hydrolysis with the movement of substances. As the rate-limiting step of the MAP, the primary function of RLIP in the plasma membrane is to catalyze the ATP-dependent efflux of unmetabolized drugs and toxins, including glutathione (GSH) conjugates of electrophilic toxins (GS-Es), which are the precursors of mercapturic acids. Clathrin-dependent endocytosis (CDE) is an essential mechanism for internalizing ligand-receptor complexes that promote tumor cell proliferation through autocrine stimulation (Wnt5a, PDGF, ßFGF, TNFα) or paracrine stimulation by hormones produced by fibroblasts (IGF1, HGF) or inflammatory cells (IL8). Aberrant functioning of these pathways appears critical for melanoma cell invasion, metastasis, and evasion of apoptosis. This review focuses on the selective depletion or inhibition of RLIP as a highly effective targeted therapy for melanoma that could cause the simultaneous disruption of the MAP and critical peptide hormone signaling that relies on CDE.