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Kidney stones have been a long-standing health issue, contributing to renal failure, especially in co-morbid patients. There is an increasing interest in exploring natural compounds with anti-urolithiatic properties. Our study utilized in-silico techniques followed by in vivo experiments to evaluate the anti-urolithiatic potential of selected phytoconstituents. Molecular docking studies were conducted on 11 different targets, including inhibitors of kidney stone formation, antioxidant enzymes, and biomarkers of kidney injury, to explore the potential of anti-urolithiatic effects of 38 phytoconstituents from medicinal plants possessing diuretic activity. Further, the anti-urolithiatic activity of the phytoconstituent was evaluated using a sodium oxalate-induced urolithiatic fruit fly and mouse model. Hesperidin emerged as a promising candidate, exhibiting binding interactions with a specific set of 11 target proteins involved in crystal formation with minimal free energy. Hesperidin demonstrated promising anti-urolithiatic potential in mitigating urolithiasis as evidenced by reduced crystal covered area of Malpighian tubules of fruit fly and reduced blood urea nitrogen (BUN), serum creatinine and serum sodium, potassium levels in mice. Moreover, it increased urine volume, preventing crystal deposition, and reduced urine urea nitrogen, creatinine, sodium, and potassium levels, enhancing urine flow and preventing crystal accumulation. Histopathological analysis further supported its efficacy by showing minimal crystal deposition and reduced kidney damage. Hesperidin exhibited superior effectiveness in reducing various serum and urine parameters, making it promising alternatives for urolithiasis management warranting further investigation to determine its safety and optimal dosages in human.

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Objectives: The objective of the study was to propose and test a new grading system to quantify the clinical eruption of teeth into the oral cavity. In addition, the study also aimed to apply the grading system to a sample population to determine the chronology and sequence of permanent tooth eruptions, comparing the results with an existing standard table. Methods: A cross-sectional study was designed, and 1220 children aged 5-18 years were selected from five schools in Chennai. The clinical status of permanent tooth eruption was graded using the newly proposed system. The sequence and chronology of permanent tooth eruptions were determined using Probit analysis and compared with those established by Logan and Kronfeld. The difference in stages of eruption between the sexes was analyzed using the ANOVA test. Results: The study sample included 515 boys and 705 girls. A total of 23,218 permanent maxillary and mandibular teeth were examined and graded. Of the 11,085 maxillary teeth, 367 were classified as grade 1, 660 as grade 2, and 10,058 as grade 3. Similarly, of the 12,133 mandibular teeth, 497 were grade 1, 793 were grade 2, and 10,843 were grade 3. The eruption of the maxillary canines, second molars, and mandibular second premolars was observed to have occurred earlier than in the traditional table of tooth eruption. The most significant differences in the stages of eruption between the sexes were observed in the 9-12 age group. Conclusions: The newly proposed grading system was found to be simple, objective, less confusing, and more robust, compared with the existing systems in determining the clinical status of tooth eruptions. The ages of eruption of maxillary canines, second molars, and mandibular second premolars were earlier.

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PURPOSE: Immunotherapy is an emerging therapeutic modality for many autoimmune, oncology, and infectious diseases to cure or prevent the underlying causes. Several immunotherapeutic agents are investigated for their beneficial potential in patients with diabetes. However, none have culminated into a successful therapy. The present comprehensive meta-analysis and systematic review covers the last two decades of historical research evaluating the Bacillus Calmette-Guerin (BCG) vaccine as an immunotherapeutic agent in diabetes, along with updated information on similar recent publications. METHOD: A total of 278 articles were retrieved through literature databases, and after applying inclusion and exclusion criteria as per PRISMA guidelines, seven studies were selected for meta-analysis using Cochrane Q statistics. RESULTS: Our meta-analysis revealed marginal benefits, lowering glycosylated/glycated haemoglobin (HbA1C) levels and glutamic-acid-decarboxylase (GAD) autoantibodies in BCG treated people with Type 1 Diabetes (T1D) compared to the matched control individuals. The BCG intervention found to be ineffective in regulating C-peptide (connecting peptide) and clinical remission (CR) i.e. improved glycemic regulation, though beneficial tendency was observed. CONCLUSION: Our systematic review and meta-analysis revealed benefits of BCG vaccine intervention in T1D patients, including improved HbA1C and GAD autoantibody levels. However, the study has several limitations stemming from BCG vaccine-related factors and patient characteristics. Therefore, a large clinical trial with an enhanced study design is needed to validate the immunity-related benefits of the BCG vaccine for glucose metabolism in patients with T1D.

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At present, healthcare systems around the world are confronted with unprecedented challenges caused by aging demographics, increasing chronic diseases, and resource challenges. In this scenario, artificial intelligence (AI) emerges as a disruptive technology that can provide solutions to these complicated problems. This review article outlines the vital role played by AI in altering the health landscape. The constant demand for effective and accessible healthcare demands the use of new solutions. AI can be described as an important imperative, enabling advancements in many areas of the delivery of healthcare. This review article explores the possibilities of use of AI to aid in the field of healthcare assistants, diagnosing, disease prediction, and personalized treatment and the discovery of drugs, telemedicine and remote monitoring of patients, robotic-assisted procedures imaging for pathology and radiology analysis, and the analysis of genomic data. By analyzing the existing research and cases, we explain how AI-driven technology can optimize processes in healthcare, improve diagnosis accuracy, improve the quality of treatment, and simplify administrative tasks. By highlighting the most successful AI applications and laying out possible future developments, the review article will provide insight for healthcare professionals, policymakers, researchers, and other stakeholders in harnessing the power of AI to transform healthcare delivery and enhance the quality of care for patients.

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BACKGROUND: Reducing overweight and obesity has been a longstanding focus of public health messaging and physician-patient interactions. Clinical guidelines by major public health organizations describe both overweight and obesity as risk factors for mortality and other health conditions. Accordingly, a majority of primary care physicians believe that overweight BMI (even without obesity) strongly increases mortality risk. MAIN POINTS: The current evidence base suggests that although both obese BMI and underweight BMI are consistently associated with increased all-cause mortality, overweight BMI (without obesity) is not meaningfully associated with increased mortality. In fact, a number of studies suggest modest protective, rather than detrimental, associations of overweight BMI with all-cause mortality. Given this current evidence base, clinical guidelines and physician perceptions substantially overstate all-cause mortality risks associated with the range of BMIs classified as "overweight" but not "obese." Discrepancies between evidence and communication regarding mortality raise the question of whether similar discrepancies exist for other health outcomes. CONCLUSIONS: Health communication that inaccurately conveys current evidence may do more harm than good; this applies to communication from health authorities to health practitioners as well as to communication from health practitioners to individual patients. We give three recommendations to better align health communication with the current evidence. First, recommendations to the public and health practitioners should distinguish overweight from obese BMI and at this time should not describe overweight BMI as a risk factor for all-cause mortality. Second, primary care physicians' widespread misconceptions about overweight BMI should be rectified. Third, the evidence basis for other potential risks or benefits of overweight BMI should be rigorously examined and incorporated appropriately into health communication.

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BACKGROUND: Smartphones have become an indispensable part of almost everyone's life. India has now become the leading and second-largest Smartphone market in the world. It has been noted that the purpose of Smartphone usage has exceptionally changed over the past few years, especially among students, professionals, and the common man. Smartphones have now become essential and the need of the hour, and medical students are no exception. Smartphones can make "smart students smarter"! There are now 10,275 unique applications labeled under the "Medical" and "Healthcare and Fitness" categories. The common medical applications used are MedCalc, Drug Infusion, Flashcards, Encyclopedia, Merck Manual, Medscape, PubMed, Epocrates, MedlinePlus, Lab test applications, Medical Dictionary, Eponyms etc. Despite the advantages and needs of smartphones, they have proven to be a source of potential hazard to human health, not only physical but also mental, social, and emotional well-being. There is consistent evidence for co-morbidity (such as obesity, heart diseases, neck and back pain, etc.) between excessive smartphone use and other psychiatric disorders, such as depression, anxiety, obsessive and compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD) similar to internet addiction. The significant association of this addiction with poorer sleep quality and higher perceived stress has been a cause for concern. Hence, further investigation to explore the association between smartphone addiction and mental health, this study was undertaken. MATERIALS AND METHODS: Our study was undertaken in Dr VMGMC, Solapur, from June to August 2022, after obtaining approval from the ethical committee, approval number 172/22. Total voluntary participation for the study was 600 (from first to final year), and accordingly convenient sample size was taken. RESULTS: We found that out of the total participants, 42% of the participants had an average screen time of 4-6 h daily. A very small percentage of participants (4%) spent less than two hours in front of a screen. Alarmingly, 65% of the participants had an average screen time of more than 4 hours, which puts them at risk for the negative health impacts of prolonged screen time. Around 12% of them had symptoms of mild stress, 10.3% for mild anxiety, and 15.6% for mild depression. 10.6% had symptoms of moderate stress, 23.3% for moderate anxiety, and 16% for moderate depression. A small proportion of undergraduates, that is, 5%, 16%, and 11.6%, had symptoms of severe and extremely severe stress, anxiety, and depression, respectively. CONCLUSION: The study participants did not feel a lot of stress, anxiety, or depression symptoms when smartphones were used judiciously and mostly for non-social purposes (such as studying, listening to music, or watching videos). This investigation led us to the conclusion that there are some positive effects of smartphones on mental health. However, those who spent an excessive amount of time on their smartphones for social contact, with an average screen time of 5 h, showed signs of mild to moderate sadness, moderate anxiety, and tension, demonstrating that social media had a negative impact on the mental health of medical undergraduates. Therefore, efforts should be made to inform medical students about how using a smartphone is harming their mental health.

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OBJECTIVES: Population-based variations have been reported in permanent teeth eruption but only sparse literature exists on the same. A systematic review and meta-analysis were performed to assess the global variations in eruption chronology of permanent teeth in children and adolescents and the role of sexes, jaws and classes of socio-economic status (SES) on timing of eruption was explored. METHODS: The protocol for the systematic review was registered in PROSPERO. An extensive search of PubMed, EMBASE, Google Scholar, EBSCO, Cochrane library, and anthropology databases was carried out until April 2023. Additionally, grey literature search and hand-searching of relevant key journals was done. RESULTS: Overall, 3797 cross-sectional and longitudinal studies were retrieved from multiple databases. A total of 939, 191 participants were included from 80 studies of which, 41 were carried out in Asia, 26 in Europe, 5 in Africa, 4 in North America, and 4 in Oceania. The mandibular first molar eruption was found to be as early as 4.09 years while the maxillary second molar erupted as late as 13.45 years. Using a random effects model, 28 forest plots were generated. Meta-regression interpreted tooth eruption to be earlier in females and in the mandible. CONCLUSIONS: The findings of this study show that the ages of permanent teeth eruption was advanced in the European population followed by Africa and Asia.

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AIM: This study aims to evaluate the long-term treatment outcome of conventional and hypofractionation radiotherapy in postmastectomy cancer breast patients. MATERIAL AND METHODS: A total of 140 postmastectomy breast cancer patients were included in this retrospective study, who were treated from 2012 to 2014 with chemotherapy and various fractionation radiotherapy schedules. Radiotherapy treatment records for study group-I received radiotherapy 4256 cGy in 16 fractions over 3½ weeks, group-II patients received 4005 cGy in 15 fractions over 3 weeks, and conventional radiotherapy group-III received 5000 cGy in 25 fractions over 5 weeks. RESULTS: The median follow-up of patients from all groups was 60 months (range 9 to 111 months). There were 39 cases with disease failure, 13 (26%) in group I (42.56 Gy), 16 (40%) in group II (40.05 Gy), and 10 (20%) in group III (50 Gy). There were 4 locoregional recurrences (LRRs), two isolated, and 11 distant failures in group I, 3 LRRs (1 isolated LRR) and 15 distant failures in group II, and only one LRR and 9 distant failures in group III. The disease-free survival (DFS) were 74%, 60%, and 80%, respectively, in groups I, II, and III (P =0.044). CONCLUSION: The long-term results of this study show that hypofractionation radiotherapy in postmastectomy cases is well tolerated and acute and late side effects are also comparable to conventional fractionation. In our study, locoregional and distant failure seems slightly higher with hypofractionation schedules than in other studies, highlighting the need for more studies with long-term follow-up in postmastectomy patients.

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SIGNIFICANCE STATEMENT: Metabolic acidosis is a common complication of CKD and is associated with more rapid decline of kidney function, but well-powered controlled randomized trials testing the effect of treating metabolic acidosis on slowing CKD progression have not been conducted. The VALOR-CKD study randomized 1480 individuals with CKD and metabolic acidosis, across 320 sites to placebo or veverimer (a novel hydrochloric acid binder). The findings did not demonstrate the efficacy of veverimer in slowing CKD progression, but the difference in serum bicarbonate between placebo and drug arms was only approximately 1 mEq/L. Veverimer was safe and well tolerated. BACKGROUND: Metabolic acidosis is common in CKD, but whether its treatment slows CKD progression is unknown. Veverimer, a novel hydrochloric acid binder that removes acid from the gastrointestinal tract, leads to an increase in serum bicarbonate. METHODS: In a phase 3, double-blind, placebo-controlled trial, patients with CKD (eGFR of 20-40 ml/min per 1.73 m 2 ) and metabolic acidosis (serum bicarbonate of 12-20 mEq/L) from 35 countries were randomized to veverimer or placebo. The primary outcome was the composite end point of CKD progression, defined as the development of ESKD (kidney transplantation or maintenance dialysis), a sustained decline in eGFR of ≥40% from baseline, or death due to kidney failure. RESULTS: The mean (±SD) baseline eGFR was 29.2±6.3 ml/min per 1.73 m 2 , and serum bicarbonate was 17.5±1.4 mEq/L; this increased to 23.4±2.0 mEq/L after the active treatment run-in. After randomized withdrawal, the mean serum bicarbonate was 22.0±3.0 mEq/L and 20.9±3.3 mEq/L in the veverimer and placebo groups at month 3, and this approximately 1 mEq/L difference remained stable for the first 24 months. A primary end point event occurred in 149/741 and 148/739 patients in the veverimer and placebo groups, respectively (hazard ratio, 0.99; 95% confidence interval, 0.8 to 1.2; P = 0.90). Serious and overall adverse event incidence did not differ between the groups. CONCLUSIONS: Among patients with CKD and metabolic acidosis, treatment with veverimer did not slow CKD progression. The lower than expected bicarbonate separation may have hindered the ability to test the hypothesis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: VALOR-CKD, NCT03710291 .

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OBJECTIVES: This systematic review aimed to assess global variations in the eruption chronology of primary teeth in children and the role of sexes, jaws, and socio-economic status on eruption timing. DESIGN: An extensive search of electronic databases, grey literature, and hand-searching was carried out until April 2023 RESULTS: A total of 42,109 children, with an age range of 0-83 months were included from 42 studies (22 in Asia, 7 in Europe, 5 in Africa, 4 in North America, 3 in Oceania and 1 in South America). The mandibular central incisor was the first tooth to erupt at 6 months in North America and 13.5 months in Asia while the mandibular second molar erupted at 20.1 months in Europe and 29 months in South America. CONCLUSIONS: The age of primary teeth eruption was advanced in the European population followed by North America, Africa, Oceania, and Asia while it was delayed in the South American population. Meta-analysis showed that tooth eruption was earlier in the left quadrant than the right but the role of other factors (sexes, jaws, and socio-economic status) was insignificant. Population-specific data on primary teeth emergence may serve as a baseline for future research. In clinical practice, these population-based eruption charts can serve as a valuable asset for diagnosis and treatment planning in children.

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INTRODUCTION: Anxiety and stress are challenging conditions that result in perturbation of the body's homeostasis. It disturbs one's physical and mental state of equilibrium. There are many ways to overcome anxiety and stress, however, the best among many remedies is yoganidra, as it achieves optimum functioning of not only our body but also our mind. Hence, the present study was planned to evaluate the impact of yoganidra practice on the anxiety levels of undergraduate students. AIMS AND OBJECTIVES: This study aimed to evaluate physiological parameters like pulse rate, blood pressure, and respiratory rate, measure anxiety levels by the general anxiety disorder-7 (GAD-7) inventory and Beck's anxiety questionnaire, conduct yoganidra sessions for all the students, and compare the effects of these training sessions on physiological parameters and anxiety scales. MATERIALS AND METHODS: The present study was carried out in the department of physiology, R.V.M. Institute of Medical Sciences and Research Center, Siddipet, and conducted on 125 students from first to final Bachelor of Medicine, Bachelor of Surgery who participated voluntarily and actively after satisfying the inclusion and exclusion criteria. All the members were assessed for physiological cardio-respiratory parameters followed by the GAD-7 scale and Beck's anxiety questionnaire pre- and post-yoganidra sessions. RESULTS: There was a significant difference in blood pressure before and after the session, whereas the pulse rate and respiratory rate reduction after the session were highly significant. There was a highly significant reduction in GAD-7 anxiety score, from 12±3.41 to 5.80±2.56 (p<0.0001); while for Beck's score, there was a highly significant reduction in anxiety score of 20.83±0.73 after giving yoganidra training as opposed to the earlier score of 23.75±1.86 (p<0.0001). CONCLUSION: Yoganidra provides ways to manage stress and anxiety and enhance mental wellness. It is supported by research evidence as a safe and effective method to reduce anxiety.

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Bone is one of the most complex, inaccessible body structures, responsible for calcium storage and haematopoiesis. The second highest cause of death across the world is cancer. Amongst all the types of cancers, bone cancer treatment modalities are limited due to the structural complexity and inaccessibility of bones. The worldwide incidence of bone diseases and bone defects due to cancer, infection, trauma, age-related bone degeneration is increasing. Currently different conventional therapies are available for bone cancer such as chemotherapy, surgery and radiotherapy, but they have several disadvantages associated with them. Nanomedicine is being extensively researched as viable therapeutics to mitigate drug resistance in cancer therapy and promote bone regeneration. Several natural polymers such as chitosan, dextran, alginate, hyaluronic acid, and synthetic polymers like polyglycolic acid, poly(lactic-co-glycolic acid), polycaprolactone are investigated for their application in nanomedicine for bone cancer treatment and bone regeneration. Nanocarriers have shown promising results in preclinical experimental studies. However, they still face a major drawback of inadequate targetability. The paper summarizes the status of research and the progress made so far in modifications and functionalization of natural polymers for improving their site specificity and targeting for effective treatment of bone cancer and enhancing bone regeneration.

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Background: Nicotine replacement therapy (NRT) and habit cessation counseling are considered the mainstay treatment for high nicotine dependence smokers. However, adherence to NRT is very poor. Among the NRTs, nicotine gums and nicotine patches are the most widely available. This study mainly evaluates the efficacy of nicotine gum and nicotine patches as NRT using salivary cotinine levels as a biochemical validation measure. Materials and Methods: A cross-sectional study was conducted on 72 known smokers who were willing to receive nicotine replacement therapy for cessation of smoking habits. The sample was divided into two groups: Group 1 tobacco smokers were offered nicotine chewing gum, and group 2 tobacco smokers were offered nicotine patches. Both groups received treatment for 12 weeks. At baseline and at the end of the trial period, the saliva samples were analyzed for cotinine levels using an enzyme-linked immunosorbent assay (ELISA). The severity of smoking was assessed using the Fagerstrom Test for Nicotine Dependence (FTND). Results: The quit rate was higher in the nicotine patch group compared with the nicotine gum group. On comparison of week one vs week twelve in the nicotine group nicotine gum group showed (CI: 18.10 to 13.83) and in the patch group (CI: 7.754 to 6.56) with P < 0.001. The pre- and post-cotinine estimation was significantly reduced for nicotine patches compared with nicotine gums, and patient compliance also yielded better results for nicotine patches. Conclusion: This study depicts that nicotine patches were better adhered to in comparison with nicotine gums, and salivary cotinine level is an effective biochemical validation measure.

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Globally, we are seeing a rise in non-communicable diseases such as obesity, hypertension, diabetes, metabolic syndrome, chronic respiratory diseases, cancer, etc., due to stressful lifestyle in this competitive world. Most of the non-communicable diseases are associated with lifestyle behavior. Presently, the role of lifestyle medicine is very critical and important in the management of chronic lifestyle-associated disorders. Considering the above facts, we decided to review the literature to gain a deeper insight into the implications of lifestyle medicine in medical practice. A literature search was conducted on PubMed, Scopus and Google Scholar databases. We observed that lifestyle medicine intervention is a growing and newer discipline and is being employed along with conventional management of non-communicable diseases by medical practitioners today, as they are strongly associated with lifestyle behaviors and practices. Motivation for change in lifestyle is challenging because it depends on the patient's determination and eagerness to adapt and accommodate to the newer lifestyle pattern. The medical practitioners should spend time in coaching patients on lifestyle-related health education. Guidance and coaching by medical practitioners will help patients adapt to practices of maintaining regular physical activity, a balanced diet, good sleep hygiene, and avoid addictions of tobacco and alcohol as part of life. Introducing real and progressive evidence-based behavioral changes to reduce the risks of lifestyle-related acute and chronic diseases in medical practice will reduce the burden of non-communicable disease.

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Background: To evaluate the relation between serum-25-hydroxy Vitamin-D levels (S25OHVDL) and concurrent chemoradiation therapy (CTRT) toxicities in patients of head and neck squamous cell cancer (HNSCC). Methods: After an institutional ethics committee approval, consecutive HNSCC patients who received radical/adjuvant CTRT were prospectively evaluated. Patients were assessed for CTRT toxicities using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE-v5.0) and the response was evaluated according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST-1.1). S25OHVDL was assessed at the time of the first follow-up. Patients were divided into group A (Optimal) and group B (suboptimal) according to S25OHVDL. The treatment toxicities were correlated with S25OHVDL. Results: Twenty-eight patients were evaluated for the study. S25OHVDL was optimal in eight (28.57%) and suboptimal in 20 patients (71.42%). Mucositis and radiation dermatitis were significantly more in subgroup B (P-value 0.0011 and 0.0505, respectively). Relatively lower but nonsignificant hemoglobin and peripheral white blood cell counts were observed in subgroup B. Conclusion: Suboptimal S25OHVDL was associated with significantly more skin and mucosal toxicities in HNSCC patients treated with CTRT.

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BACKGROUND: Whether treating metabolic acidosis slows progression of chronic kidney disease (CKD) has not been established. Veverimer is a novel hydrochloric acid binder that removes acid from the gastrointestinal tract leading to an increase in serum bicarbonate; it is being developed to treat metabolic acidosis with the goal of slowing progression of CKD. METHODS: The VALOR-CKD trial is an international, randomized, multicenter, double-blind, placebo-controlled study designed to evaluate the effect of once-daily veverimer on kidney disease progression in patients with metabolic acidosis and CKD. Eligibility criteria include a serum bicarbonate in the range of 12-20 mmol/L and an estimated glomerular filtration rate (eGFR) of 20-40 mL/min/1.73 m2. The primary outcome is kidney disease progression defined as the development of end-stage kidney disease, a sustained decline in eGFR of >40% from baseline or death due to kidney failure. Key secondary endpoints include effects on physical function. RESULTS: Between December 2018 and December 2021, 1480 participants were randomized. The mean age at baseline was 65.1 years and 42% of the patients were female. The mean baseline eGFR was 29.1 mL/min/1.73 m2 and mean serum bicarbonate was 17.5 mmol/L. The median urine albumin-to-creatinine ratio at screening was 201 mg/g and the median 5-year predicted risk of kidney failure was 32%. Diabetes and hypertension were present in 56% and 98% of participants, respectively. CONCLUSIONS: VALOR-CKD has recruited a large population of people with metabolic acidosis at high risk for CKD progression to determine the effects of veverimer on the risk of progressive loss of kidney function.

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OBJECTIVES: Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes. Our objective was to determine if children with severe DKA without alteration in mental status can be managed safely on a general children's medical unit. METHODS: Single center retrospective study of 191 patient encounters among 168 children admitted to the children's medical unit (CMU) at Primary Children's Hospital between 2007 and 2017 with severe DKA (pH <7.1 and/or bicarbonate <5 mmol/L). Chart review identified complications including death, transfer to the intensive care unit (ICU), incidence of cerebral edema, and hypoglycemia. We compared patients requiring ICU transfer with those who did not with respect to demographics, laboratory findings at presentation, therapeutic interventions, length of stay, and cost. RESULTS: Of 191 patient encounters, there were 0 deaths (0%, 95% CI 0-2.4%), 22 episodes of alteration of mental status concerning for developing cerebral edema (11.5%, 95% CI 7.7-16.9%), 19 ICU transfers (10%, 95% CI 6.4-15.1%), and 7 episodes of hypoglycemia (3.7%, 95% CI 1.6-7.5%). ICU transfer was associated lower initial pH (7.03 ± 0.06 vs. 7.07 ± 0.07, p<0.05), increased length of stay (3.0 ± 0.8 vs. 2.2 ± 0.9 days, p<0.05), and increased cost of hospitalization (mean ± SD $8,073 ± 2,042 vs. $5,217 ± 1,697, p<0.05). CONCLUSIONS: The majority of children with severe DKA without alteration in mental status can be managed safely on a medical unit. Implementing a pH cutoff may identify high-risk patients that require ICU level of care.

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INTRODUCTION: The percentage of patients initiating dialysis at an estimated glomerular filtration rate (eGFR) ≤9 mL/min/1.73 m2 decreased between 2000 and 2018 in the USA. Clinical practice guidelines recommend basing the decision to initiate dialysis primarily on uremic signs and symptoms rather than on a particular level of kidney function. However, what signs and symptoms currently practicing nephrologists consider "uremic," how they weigh eGFR and other factors in the decision to initiate dialysis have not been reported. METHODS: The study was an online survey of 255 US nephrologists, conducted between August and October 2021. RESULTS: Nearly half of respondents (49.8%) had an absolute lower eGFR (8.4 [95% CI: 7.6, 9.2] mL/min/1.73 m2) at which they would initiate dialysis in an asymptomatic patient. The top 5 symptoms that would trigger a recommendation to initiate dialysis were loss of appetite/nausea/vomiting (17%), low eGFR (10%), shortness of breath (10%), declining physical ability/function (9%), and generalized weakness (9%). Poor nutritional status and physical function decline were considered very important in the decision to initiate dialysis by 64% and 55% of respondents, respectively. Nephrologists surveyed significantly shortened the time to dialysis initiation in response to declining physical function in an otherwise asymptomatic (hypothetical) patient. CONCLUSIONS: Nearly half of nephrologists sometimes based their decision to initiate dialysis on eGFR alone. The eGFR threshold at which they did so was lower than has been examined in randomized controlled trials of dialysis initiation. Initiatives designed to safely delay dialysis through aggressive medical management could focus on modifiable factors that are the most important drivers of the decision to initiate dialysis.

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Fibrocytes are bone marrow-derived monocytic cells implicated in wound healing. Here, we identify their role in lung cancer progression/ metastasis. Selective manipulation of fibrocytes in mouse lung tumor models documents the central role of fibrocytes in boosting niche features and enhancing metastasis. Importantly, lung cancer patients show increased number of circulating fibrocytes and marked fibrocyte accumulation in the cancer niche. Using double and triple co-culture systems with human lung cancer cells, fibrocytes, macrophages and endothelial cells, we substantiate the central features of cancer-supporting niche: enhanced cancer cell proliferation and migration, macrophage activation, augmented endothelial cell sprouting and fibrocyte maturation. Upregulation of endothelin and its receptors are noted, and dual endothelin receptor blockade suppresses all cancer-supportive phenotypic alterations via acting on fibrocyte interaction with the cancer niche. We thus provide evidence for a crucial role of fibrocytes in lung cancer progression and metastasis, suggesting targets for treatment strategies.

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