Long-term treatment results of conventional and hypofractionation radiotherapy in postmastectomy cancer breast patients: A retrospective study from rural cancer center of Maharashtra, India.

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.

Global variations in eruption chronology of permanent teeth: A systematic review and meta-analysis.

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.

VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of CKD in Patients with Metabolic Acidosis.

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 .

Global variations in eruption chronology of primary teeth: A systematic review and meta-analysis.

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.

Yoganidra to Alleviate Anxiety: An Interventional Study.

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.

Modification and Functionalization of Polymers for Targeting to Bone Cancer and Bone Regeneration.

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.

Comparative evaluation of the efficacy of nicotine chewing gum and nicotine patches as nicotine replacement therapy using salivary cotinine levels as a biochemical validation measure.

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.

Implications of lifestyle medicine in medical practice.

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.

Serum 25-hydroxy vitamin-D levels in head and neck cancer chemoradiation therapy: Potential in cancer therapeutics.

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.

Outcomes of children with severe diabetic ketoacidosis managed outside of a pediatric intensive care unit.

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.

Design and population of the VALOR-CKD study: a multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of veverimer in slowing progression of chronic kidney disease in patients with metabolic acidosis.

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.

Factors Affecting the Decision to Initiate Dialysis: A National Survey of United States Nephrologists.

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.

Fibrocytes boost tumor-supportive phenotypic switches in the lung cancer niche via the endothelin system.

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.

Efficient Hybrid Blind Watermarking in DWT-DCT-SVD with Dual Biometric Features for Images.

In the modern era of virtual computers over the notional environment of computer networks, the protection of influential documents is a major concern. To bring out this motto, digital watermarking with biometric features plays a crucial part. It utilizes advanced technology of cuffing data into digital media, i.e., text, image, video, or audio files. The strategy of cuffing an image inside another image by applying biometric features namely signature and fingerprint using watermarking techniques is the key purpose of this study. To accomplish this, a combined watermarking strategy consisting of Discrete Wavelet Transform, Discrete Cosine Transform, and Singular Value Decomposition (DWT-DCT-SVD) is projected for authentication of image that is foolproof against attacks. Here, singular values of watermark1 (fingerprint) and watermark2 (signature) are obtained by applying DWT-DCT-SVD. Affixing both the singular values of watermarks, we acquire the transformed watermark. Later, the same is applied to cover image to extract the singular values. Then we add these values to the cover image and transformed watermark to obtain a final watermarked image containing both signature and fingerprint. To upgrade the reliability, sturdiness, and originality of the image, a fusion of watermarking techniques along with dual biometric features is exhibited. The experimental results conveyed that the proposed scheme achieved an average PSNR value of about 40 dB, an average SSIM value of 0.99, and an embedded watermark resilient to various attacks in the watermarked image.

Effects of veverimer on serum bicarbonate and physical function in women with chronic kidney disease and metabolic acidosis: a subgroup analysis from a randomised, controlled trial.

BACKGROUND: Globally, the prevalence of chronic kidney disease (CKD) is higher in women than in men; however, women have been historically under-represented in nephrology clinical trials. Metabolic acidosis increases risk of progressive loss of kidney function, causes bone demineralization and muscle protein catabolism, and may be more consequential in women given their lower bone and muscle mass. Veverimer, an investigational, non-absorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as treatment for metabolic acidosis. METHODS: This was a Phase 3, multicenter, randomised, blinded, placebo-controlled trial in 196 patients with CKD (eGFR: 20-40 mL/min/1.73 m2) and metabolic acidosis who were treated for up to 1 year with veverimer or placebo. We present the findings from a pre-specified subgroup analysis evaluating the effects of veverimer on metabolic acidosis and physical function among women (N = 77) enrolled in this trial. RESULTS: At week 52, women treated with veverimer had a greater increase in mean (± standard error) serum bicarbonate than the placebo group (5.4 [0.5] vs. 2.2 [0.6] mmol/L; P < 0.0001). Physical Function reported by patients on the Kidney Disease and Quality of Life - Physical Function Domain, a measure that includes items related to walking, stair climbing, carrying groceries and other activities improved significantly in women randomized to veverimer vs placebo (+ 13.2 vs. -5.2, respectively, P < 0.0031). Objectively measured performance time on the repeated chair stand test also improved significantly in the veverimer group vs. placebo (P = 0.0002). CONCLUSIONS: Veverimer was effective in treating metabolic acidosis in women with CKD, and significantly improved how they felt and functioned. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03390842 . Registered on January 4, 2018.

Marathi translation, linguistic validation, and cross-cultural adaptation of speech handicap index and voice handicap index in patients of head and neck squamous cell cancer.

Background: Patient reported treatment outcomes is a better way to measure the quality of life (QOL). This study was undertaken to translate the speech handicap index (SHI) and voice handicap index (VHI) in Marathi language and its linguistic validation and cross-cultural adaptation in patients of head and neck squamous cell cancer (HNSCC). Methods: SHI and VHI were translated into Marathi with prior permission from the respective authors of original English questionnaire (RAs). The translation procedure for each tool included two forward translations (English to Marathi), the formation of first intermediate Marathi translation (FIT), two back translations (Marathi to English) of FIT, and interim Marathi translation (IT) formation. The second intermediate Marathi translation (SIT) was prepared after face validation of IT by a subject expert. Pretesting of SIT was done in 20 patients of HNSCC to validate linguistic and cross-cultural adaptation. By incorporating the patient's suggestions, the final Marathi translation was prepared and sent to primary authors for approval. Results: The grammatically and conceptually acceptable and face validated SIT was prepared and administered to HNSCC patients. The patients of the oral cavity and larynx were in SHI and VHI group, respectively (ten patients in each group). The questionnaire was well understood reflecting its linguistic and cross-cultural adaptation. Some of the patients suggested changes in a few words which were then corrected, rechecked with back translation, and final Marathi translated questionnaire was prepared. It was approved by RAs. Conclusion: Marathi translation of SHI and VHI are well accepted and comprehensible. It can be used for future studies.

Effects of veverimer on serum bicarbonate and physical function in diabetic patients with chronic kidney disease and metabolic acidosis: subgroup analysis from a randomized, controlled trial.

BACKGROUND: Metabolic acidosis is a complication of chronic kidney disease (CKD) that increases risk of CKD progression, and causes bone demineralization and muscle protein catabolism. Patients with diabetes are prone to metabolic acidosis and functional limitations that decrease quality of life. Veverimer, an investigational, non-absorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as treatment for metabolic acidosis. This post hoc subgroup analysis evaluated effects of veverimer on metabolic acidosis and physical function among patients with diabetes. METHODS: This was a Phase 3, multicenter, randomized, blinded, placebo-controlled trial in 196 patients with CKD (estimated glomerular filtration rate 20-40 mL/min/1.73 m2) and metabolic acidosis who were treated for up to 1 year with veverimer or placebo. RESULTS: At Week 52, veverimer-treated patients with diabetes (n = 70), had a significantly greater increase in mean serum bicarbonate than the placebo group (n = 57) (4.4 versus 2.9 mmol/L, P < 0.05). Patient-reported limitations of physical function on the Kidney Disease and Quality of Life-Physical Function Domain (e.g. walking several blocks and climbing a flight of stairs) improved significantly in the veverimer versus placebo group (+12.5 versus +0.3, respectively, P < 0.001) as did objective physical performance on the repeated chair stand test (P < 0.0001). CONCLUSIONS: Few interventions for patients with diabetes and CKD have successfully improved quality of life or physical functioning. Our study demonstrated that veverimer effectively treated metabolic acidosis in patients with diabetes and CKD, and significantly improved how these patients felt and functioned.

Clinical Utility of 24-h Ambulatory Blood Pressure Monitoring in Hospitalized Patients with Chronic Kidney Disease.

INTRODUCTION: Hypertension leads to rapid progression of kidney disease. Hypertension (HTN) is the second most common cause for CKD after diabetes. Ambulatory blood pressure monitoring (ABPM) helps in accurate and early diagnosis of HTN along with measurements of other variables, namely nondippers, reverse dippers, hyperbaric index (HBI), percentage time elevation (PTE), and early morning surge. METHODOLOGY: After obtaining the institution ethics committee approval total 192 cases, of 12-80 years age group, who were diagnosed with CKD were included in the study. ABPM was done for patients using Meditech ABPM-05 machine. RESULTS: Study showed male predominance. Maximum patients were in the age group of 41-60 years. Prevalence of Hypertension in patients with CKD was 88.02%. The systolic BP, diastolic BP, and mean arterial pressure (MAP) were significantly higher by clinic BP measurement than ABPM in all stages of patients with CKD especially in stage IV than stage V CKD. Systolic, diastolic, MAP, HBI and PTE at nighttime were significantly higher than daytime in all patients with CKD, especially in patients with resistant hypertension. Prevalence of whitecoat HTN (4.1%), whitecoat effect (16.1%), resistant hypertension (39.6%), masked HTN (1%), and masked uncontrolled HTN (10.4%) was noted. Systolic and diastolic HBI was lower in patients on hemodialysis as compared to those not on hemodialysis. Non-dippers were more than dippers. CONCLUSION: Apart from mean systolic and diastolic BP, ABPM gives the extent of end-organ damage and insights into the need for control of 24 h BP in patients of CKD.

Ziltivekimab for Treatment of Anemia of Inflammation in Patients on Hemodialysis: Results from a Phase 1/2 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Patients with CKD who are on hemodialysis are hyporesponsive to erythropoiesis-stimulating agents (ESAs) because of anemia of inflammation. Interleukin-6 (IL-6) induced hepcidin expression is a key mediator of such inflammation. METHODS: This phase 1/2, placebo-controlled trial assessed effects of ziltivekimab, a novel anti-IL-6 ligand antibody, in patients on hemodialysis with rs855791, a single nucleotide polymorphism of the TMPRSS6 gene that is hypothesized to heighten susceptibility to IL-6-mediated inflammatory effects. After a screening period documenting stable ESA and iron dosing, we randomized 61 patients with elevated IL-6 (≥4 pg/ml) to receive placebo or ziltivekimab (doses of 2, 6, or 20 mg), administered intravenously every 2 weeks for 12 weeks during hemodialysis. ESA dose adjustments were allowed after 4 weeks. We analyzed safety and effects on inflammation, iron metabolism, serum albumin, and anti-drug antibodies. RESULTS: No patient experienced dose-limiting toxicity. Four patients (two each in the 6- and 20-mg cohorts) died of a treatment-emergent adverse event. Compared with patients receiving placebo, those receiving ziltivekimab experienced significantly greater reductions of high-sensitivity C-reactive protein, serum amyloid A, and fibrinogen from baseline to end of treatment. Median ESA usage decreased by 15,000, 15,000, or 33,000 IU/wk per patient in the 2-, 6-, and 20-mg ziltivekimab cohorts, respectively, compared with no change in the placebo group. We also noted significant dose responses for decreased ESA resistance index and increased serum iron, total iron binding capacity, transferrin saturation, and serum albumin. CONCLUSIONS: Ziltivekimab significantly improved markers of inflammation, reduced ESA requirements, and increased serum albumin in patients on hemodialysis with inflammation and hyporesponsiveness to ESA therapy. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of COR-001, NCT02868229.