A next-generation BRAF inhibitor overcomes resistance to BRAF inhibition in patients with BRAF-mutant cancers using pharmacokinetics-informed dose escalation.

RAF inhibitors have transformed treatment for BRAF V600-mutant cancer patients, but clinical benefit is limited by adaptive induction of ERK signaling, genetic alterations that induce BRAF V600 dimerization, and poor brain penetration. Next-generation pan-RAF dimer inhibitors are limited by narrow therapeutic index. PF-07799933 (ARRY-440) is a brain-penetrant, selective, pan-mutant BRAF inhibitor. PF-07799933 inhibited signaling in vitro, disrupted endogenous mutant-BRAF:wild-type-CRAF dimers, and spared wild-type ERK signaling. PF-07799933 ± binimetinib inhibited growth of mouse xenograft tumors driven by mutant BRAF that functions as dimers and by BRAF V600E with acquired resistance to current RAF inhibitors. We treated patients with treatment-refractory BRAF-mutant solid tumors in a first-in-human clinical trial (NCT05355701) that utilized a novel, flexible, pharmacokinetics-informed dose escalation design that allowed rapid achievement of PF-07799933 efficacious concentrations. PF-07799933 ± binimetinib was well-tolerated and resulted in multiple confirmed responses, systemically and in the brain, in BRAF-mutant cancer patients refractory to approved RAF inhibitors.

In vitro profiling and molecular dynamics simulation studies of berberine loaded MCM-41 mesoporous silica nanoparticles to prevent neuronal apoptosis.

Neuronal loss in Alzheimer's disease has been reported to display features of apoptosis, pyroptosis (programmed necrosis), or necroptosis. This study thoroughly examines the production and characterization of MCM-41 based berberine (BBR)-loaded porous silica nanoparticles (MSNs) by a modified Stöber method, focusing on their possible role in inhibiting the apoptotic process. Particle size, polydispersity index, morphology, drug loading, zeta potential, entrapment efficiency, and drug release were examined. The formulation was analyzed using various spectroscopic techniques. The surface area was computed by the Brunauer-Emmett-Teller plot. Computational models were developed for molecular dynamics simulation studies. A small PDI value indicated an even distribution of particles at nanoscale sizes (80-100 nm). Results from XRD and SEAD experiments confirmed the amorphous nature of BBR in nanoparticles. Nanoparticles had high entrapment (75.21 ± 1.55%) and drug loading (28.16 ± 2.5%) efficiencies. A negative zeta potential value (-36.861.1 mV) indicates the presence of silanol groups on the surface of silica. AFM findings reveal bumps due to the surface drug that contributed to the improved roughness of the MSNs-BBR surface. Thermal gravimetric analysis confirmed the presence of BBR in MSNs. Drug release was controlled by simple diffusion or quasi-diffusion. Molecular dynamics simulations confirmed the existence of diffused drug molecules. Cellular studies using SH-SY-5Y cells revealed dose-dependent growth inhibition. Fragmented cell nuclei and nuclear apoptotic bodies in DAPI-stained cells exposed to nanoparticles showed an increase in apoptotic cells. Flow cytometry analysis demonstrated a lower red-to-green ratio in SH-SY-5Y cells treated with nanoparticles. This suggests improved mitochondrial health, cellular viability restoration, and prevention of the apoptotic process. This study provides essential data on the synthesis and potential of MSNs loaded with BBR, which may serve as a viable therapeutic intervention for conditions associated with apoptosis.

Burden of COVID-19 pandemic on tuberculosis hospitalisation patterns at a tertiary care hospital in Rajasthan, India: a retrospective analysis.

OBJECTIVE: This study aimed to investigate the burden of the COVID-19 pandemic on tuberculosis (TB) trends, patient demographics, disease types and hospitalisation duration within the Respiratory Medicine Department over three distinct phases: pre-COVID-19, COVID-19 and post-COVID-19. DESIGN: Retrospective analysis using electronic medical records of patients with TB admitted between June 2018 and June 2023 was done to explore the impact of COVID-19 on patients with TB. The study employed a meticulous segmentation into pre-COVID-19, COVID-19 and post-COVID-19 eras. SETTING: National Institute of Medical Science Hospital in Jaipur, Rajasthan, India. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome includes patients admitted to the Respiratory Medicine Department of the hospital and secondary outcome involves the duration of hospital stay. RESULTS: The study encompassed 1845 subjects across the three eras, revealing a reduction in TB incidence during the post-COVID-19 era compared with the pre-COVID-19 period (p<0.01). Substantial demographic shifts were observed, with 5.2% decline in TB incidence among males in the post-COVID-19 era (n=529) compared with the pre-COVID-19 era (n=606). Despite the decrease, overall TB incidence remained significantly higher in males (n=1460) than females (n=385), with consistently elevated rates in rural (65.8%) as compared with the urban areas (34.2%). Extended hospital stays were noted in the post-COVID-19 era compared with the pre-COVID-19 era (p<0.01). CONCLUSION: The study underscores the influence of the COVID-19 pandemic on the TB landscape and hospitalisation dynamics. Notably, patient burden of TB declined during the COVID-19 era, with a decline in the post-COVID-19 era compared with the pre-COVID-19 era. Prolonged hospitalisation in the post-COVID-19 period indicates the need for adaptive healthcare strategies and the formulation of public health policies in a post-pandemic context. These findings contribute to a comprehensive understanding of the evolving TB scenario, emphasising the necessity for tailored healthcare approaches in the aftermath of a global health crisis.

Cost-comparison of robotic versus laparoscopic colorectal resections: a mapped systematic review and meta-analysis of published studies.

Background: Robotic colorectal resections (RCR) have been gaining popularity recently due to several advantages in addition to oncological safety. The objective of this review is to evaluate the cost comparison of RCR versus laparoscopic colorectal resections (LCR). Methods: All types of comparative studies reporting the cost of RCR versus LCR were retrieved from the search of standard medical electronic databases and analysis was conducted by using the principles of meta-analysis on the statistical software RevMan version 5. Results: The search of medical databases yielded 13 studies (one randomised trial and 12 comparative studies) on 16,082 patients undergoing oncological and non-oncological colorectal resections. Eleven studies reported total cost whereas seven studies reported only operative cost. In the random effects model analysis, LCR was associated with the reduced total cost [standardised mean difference -62.34, 95% confidence interval (CI): -75.14 to -49.54, Z=9.55, P<0.001] as well as reduced operative cost (standardised mean difference -4.60, 95% CI: -5.90 to -3.31, Z=6.96, P<0.001) compared to RCR. However, there was significant heterogeneity [Tau2=346.74, Chi2=29,559.11, df =11 (P<0.001; I2=100%); Tau2=2.73, Chi2=832.21, df =6 (P<0.001; I2=99%)] among included studies. Conclusions: The LCR seems to be more economical as compared to the RCR in terms of operative cost as well as total cost (operative plus in-patient stay). However, due to statistically significant heterogeneity among included studies and paucity of the randomised trials, these findings should be taken cautiously.

Prevalence of breast cancer in rural population of Jaipur: a survey-based observational study.

Breast cancer, a global health concern predominantly affecting women, recorded 2.3 million new cases and 685,000 deaths in 2020. Alarmingly, projections suggest that by 2040, there could be over 3 million new cases and 1 million deaths. To assess breast cancer prevalence in 24 rural villages within a 60 km radius of NIMS Hospital, Tala Mod, Jaipur, Rajasthan, North India 303,121. A study involving 2023 participants conducted initial screenings, and positive cases underwent further tests, including ultrasound, mammography, and biopsy. SPSSv28 analysed collected data. Among 2023 subjects, 3 screened positive for breast lumps. Subsequent clinical examination and biopsy identified 1 normal case and 2 with breast cancer, resulting in a prevalence proportion of 0.0009 or 98 per 100,000. This study helps fill gap in breast cancer prevalence data for rural Rajasthan. The results highlight a concerning prevalence of breast cancer in the rural area near NIMS hospital, emphasizing the urgent need for increased awareness, early detection, and better healthcare access. Challenges like limited resources, awareness programs, and delayed diagnosis contribute to this high incidence. To address this, comprehensive approach is necessary, including improved screening programs and healthcare facilities in rural areas. Prioritizing rural healthcare and evidence-based strategies can reduce the burden of breast cancer and improve health outcomes.

Successful treatment with fludarabine and cyclophosphamide in a VEXAS syndrome patient with associated myelodysplastic syndrome: a case report and systematic review.

Vacuoles, E1 syndrome, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a chronic inflammatory disorder that affects various organ systems. It is associated with hematologic malignancies and is generally refractory to therapies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for selected patients. We report a case wherein systemic and hematological manifestations completely resolved in a patient with VEXAS and associated myelodysplastic syndrome (MDS), following the administration of fludarabine and cyclophosphamide as part of the preparation for allo-HSCT. We conducted a systematic literature review and included 86 patients with VEXAS syndrome and associated MDS. Most cases presented with musculoskeletal involvement (71%) and anemia (72%) with lower-risk MDS. Most patients responded to corticosteroids (CS) but had a recurrence of symptoms with CS taper and were refractory to other immunosuppressive agents. Hypomethylating agents and Janus kinase inhibitors achieved a complete response in some cases. Further research is needed to develop more effective treatment strategies.

Ultrasonic-assisted extraction and UHPLC determination of ascorbic acid, polyphenols, and half-maximum effective concentration in Citrus medica and Ziziphus spina-christi fruits using multivariate experimental design.

This study aimed to determine the concentrations of ascorbic acid and polyphenols in fruits and peels of Citrus medica and Ziziphus spina-christi grown in Ethiopia. Conditions of ultrasound-assisted extraction (UAE) and ultra-high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD) were optimized, using a multivariate experimental design. The optimum conditions of UAE were 15 min extraction time at 35 ℃, with 75 % aqueous methanol as solvent, and a fruit powder-to-solvent ratio (m/v) of 1:15. Among the different drying conditions investigated, freeze-drying was found to be appropriate for analyzing ascorbic acid, polyphenols, and antioxidant potential. The overall ranges, across the fruits and peels, of ascorbic acid, total polyphenols, and antioxidant potentials (EC50) obtained were 8.7 ± 1.4-91.2 ± 2.6 mg/100 g, 253.0 ± 6.3-764.1 ± 25.8 mg GAE/100 g and 2.4 ± 0.1-26.1 ± 2.9 mg/mL, respectively. This indicates that the fruits and peels of the studied plants are advantageous as sources of ascorbic acid and polyphenols.

Racial/ethnic differences in 21-gene recurrence score and survival among patients with estrogen receptor-positive breast cancer.

BACKGROUND: Despite numerous studies on racial/ethnic disparities among patients with breast cancer, there is a paucity of literature evaluating racial/ethnic differences in 21-gene recurrence score (RS) and survival differences stratified by RS risk categories. We thus performed an observational cohort study to examine racial/ethnic disparities in the context of RS. METHODS: The National Cancer Database (NCDB) was queried for female patients diagnosed between 2006 and 2018 with estrogen receptor (ER)-positive, pT1-3N0-1aM0 breast cancer who received surgery followed by adjuvant endocrine therapy and had RS data available. Logistic multivariable analysis (MVA) was built to evaluate variables associated with RS ≥ 26. Cox MVA was used to evaluate OS. Subgroup analyses were performed to compare the magnitude of racial/ethnic differences stratified by RS. P values less than 0.017 were considered statistically significant based on Bonferroni correction. RESULTS: A total of 140,133 women were included for analysis. Of these, 115,651 (82.5%), 8,213 (5.9%), 10,814 (7.7%), and 5,455 (3.9%) were NHW, Hispanic, Black, and API women, respectively. Median (IQR) follow up was 66.2 months (48.0-89.8). Logistic MVA showed that, compared with NHW women, Black women were associated with higher RS (≥ 26 vs < 26: adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 1.12-1.26, p < 0.001), while HW (aOR 0.93, 95% CI 0.86-1.00, p = 0.04) and API women (aOR 1.03, 95% CI 0.95-1.13, p = 0.45) were not. Cox MVA showed that, compared with NHW women, Black women had worse OS (adjusted hazards ratio [aHR] 1.10, 95% CI 1.02-1.19, p = 0.012), while HW (aHR 0.85, 95% CI 0.77-0.94, p = 0.001) and API (aHR 0.66, 95% CI 0.56-0.77, p < 0.001) women had better OS. In subgroup analysis, similar findings were noted among those with RS < 26, while only API women were associated with improved OS among others with RS ≥ 26. CONCLUSION: To our knowledge, this is the largest study using nationwide oncology database to suggest that Black women were associated with higher RS, while HW and API women were not. It also suggested that Black women were associated with worse OS among those with RS < 26, while API women were associated with improved OS regardless of RS when compared to NHW women.

Use of Endpoints in Phase III Randomized Controlled Trials for Hematopoietic Stem Cell Transplantation Over the Last 15 Years: A Systematic Review.

This systematic review aimed to evaluate the proportion of primary and secondary endpoints in hematopoietic stem cell transplant (HSCT) phase III randomized clinical trials (RCTs) and analyze their trends in time and study sponsorship status. The Chi-square test and logistic regression analyses were performed using SPSS version 28. A total of 147 HSCT phase III RCTs from 2006 to 2021 reported 197 primary and 600 secondary endpoints. Overall survival (OS, 17 %), progression-free survival (PFS, 15 %), graft versus host disease (GVHD, 8 %), event-free survival (EFS, 8 %), and organ function (8 %) were the most common primary endpoints. GVHD (12.3 %, n = 74), safety/toxicity/adverse events (11.8 %, n = 71), OS (11.5 %, n = 69), PFS (9.3 %, n = 56), and relapse rate (RR; 7.5 %, n = 45) were the most common secondary endpoints during 2006-2021. After 2013, an increase was noted in the use of PFS as a primary endpoint (12 %-18 %, p = 0.196), while the use of OS as a primary endpoint declined (20 %-13 %, p = 0.170). An increase was observed in using the secondary endpoints RR (5 %-10 %, p = 0.047) and NRM (3 %-6 %, p = 0.047). EFS was used more (14 % vs. 4 %, p = 0.012) than ORR (11 % vs. 2 %, p = 0.003) as a primary endpoint in pharmaceutical-compared to non-pharmaceutical-sponsored studies. As secondary endpoints, the use of EFS (4 % vs. 1 %, p = 0.013) and ORR (4 % vs. 1 %, p = 0.028) was higher, whereas that of organ systems/functions (1.5 % vs. 5.5 %, p = 0.022) and GVHD (6.5 % vs. 15 %, p = 0.002) was lower in pharmaceutical-compared to non-pharmaceutical sponsored studies. GVHD-free relapse-free survival was reported as a primary endpoint in 2 % of studies, while only 5 % reported quality of life as a secondary endpoint. We described commonly used endpoints in HSCT phase III RCTs and patterns in their use over time by funding source and study intervention category.

Association of Insomnia and Obstructive Sleep Apnea with Worse Oral Mucositis and Quality of Life in Head and Neck Cancer Patients Undergoing Radiation Therapy.

BACKGROUND: Patients with head and neck cancer (HNC) undergoing radiation therapy (RT) often experience sleep disturbances that may contribute to oral mucositis (OM) and quality of life (QOL). METHODS: Patients with HNC treated with RT at a single institution were examined. Sleep questionnaires were given on the first day of RT to assess for insomnia and obstructive sleep apnea (OSA). Patient-reported QOL and oral mucositis were assessed during RT. Associations between insomnia and OSA with QOL were assessed using the Mann-Whitney U test. Linear mixed models assessed associations with OM. RESULTS: Among 87 patients, 34 patients (39%) had subthreshold or greater insomnia and 47 patients (54%) screened positive for OSA. Upon RT completion, patients with subthreshold or greater insomnia had worse physical function (p = 0.005), fatigue (p = 0.01), insomnia (p < 0.001), and sticky saliva (p = 0.002). Patients screening positive for OSA had worse physical function (p = 0.01), sticky saliva (p = 0.02), fatigue (p = 0.007), insomnia (p = 0.009), and pain (p = 0.005). Upon linear mixed model evaluation, subthreshold or greater insomnia (p = 0.01) and positive OSA screen (p = 0.002) were associated with worse OM. CONCLUSION: Insomnia and OSA are highly prevalent in patients with HNC undergoing RT. These sleep disturbances are associated with worse QOL and OM during treatment.

Gilteritinib as Post-Transplant Maintenance for Acute Myeloid Leukemia With Internal Tandem Duplication Mutation of FLT3.

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with acute myeloid leukemia (AML) harboring an internal tandem duplication mutation of FLT3 (FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS: Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS: Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION: Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

Correlation between maternal and infant vitamin B12 levels in severe malnutrition in infants under 6 months.

BACKGROUND: Malnutrition poses a significant global health challenge, affecting various age groups, with infants under 6 months being particularly vulnerable. Vitamin B12, an essential micronutrient critical for neurological development, has been identified as a key player in the overall health of both mothers and infants. AIM: To find the correlation between serum vitamin B12 levels in infants, 1-6 months of age with severe malnutrition and maternal levels at tertiary care hospitals in western Rajasthan. METHODS: The cross-sectional study was conducted in the UNICEF Regional Center of Excellence-supported Nutrition Rehabilitation Center in Rajasthan, India, through simple random sampling. One hundred ten infants with their mothers were enrolled after consent and approval from the Institutional Ethics Committee. RESULTS: Severe malnutrition predominantly affected infants aged 1-2 months, with 77% born small for gestational age and 66.4% belonging to the multiple birth order group. Serum vitamin B12 levels showed a significant positive correlation between mothers and infants (p < 0.001), while exclusive breastfeeding correlated positively with age-appropriate milestones (p = 0.033). CONCLUSION: The findings emphasize the importance of targeted interventions addressing maternal and infant nutrition, with a focus on ensuring adequate vitamin B12 levels.

Predictors of cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation: Insights from a real-world experience.

BACKGROUND: We aimed to investigate factors associated with cytomegalovirus (CMV) viremia and CMV disease and its impact on post-transplant outcomes including overall survival (OS) following allogeneic hematopoietic stem cell transplantation (Allo-SCT). METHODS: We conducted a single-center retrospective study including 452 Allo-SCT recipients (matched unrelated donor, MUD 61%; haploidentical, haplo 39%) from 2016 to 2021. Data were analyzed using SPSS v28. Descriptive (chi-square and t-test), Kaplan-Meier and regression analyses were conducted. RESULTS: The median age was 57 years. Sixty-one percent were males and 84.3% were Caucasians. CMV serostatus was positive in 59.1% of recipients. The median follow-up was 24.4 months. CMV viremia and CMV disease were observed in 181 (40%) and 32 (7%) patients, respectively. Among CMV seropositive recipients, 65% developed CMV viremia and 11% were noted to have CMV disease compared to 4% and 1% in seronegative recipients, respectively (p < 0.001). Patients with CMV disease had significantly lower OS than those without CMV disease (median 14.1 months vs. not reached, p = 0.024); however, OS was not associated with CMV viremia (median not reached in both groups, p = 0.640). Letermovir prophylaxis was used in 66% (n = 176/267) of CMV seropositive recipients, but no impact was observed on the incidence of CMV viremia or CMV disease and OS. CONCLUSIONS: CMV disease leads to significantly inferior survival after an allogeneic hematopoietic cell transplantation. Recipient CMV seropositive status was associated with the risk of CMV viremia and CMV disease, and this was not abrogated with the use of Letermovir prophylaxis.

Folate-Mediated Targeting and Controlled Release: PLGA-Encapsulated Mesoporous Silica Nanoparticles Delivering Capecitabine to Pancreatic Tumor.

The discovery of specifically tailored therapeutic delivery systems has sparked the interest of pharmaceutical researchers considering improved therapeutic effectiveness and fewer adverse effects. The current study concentrates on the design and characterization of PLGA (polylactic-co-glycolic acid) capped mesoporous silica nanoparticles (MSN)-based systems for drug delivery for pH-sensitive controlled drug release in order to achieve a targeted drug release inside the acidic tumor microenvironment. The physicochemical properties of the nanoformulations were analyzed using TEM, zeta potential, AFM, TGA, FTIR, and BET analyses in addition to DLS size. The final formed PLGA-FoA-MSN-CAP and pure MSN had sizes within the therapeutic ranges of 164.5 ± 1.8 and 110.7 ± 2.2, respectively. Morphological characterization (TEM and AFM) and elemental analysis (FTIR and XPS) confirmed the proper capping and tagging of PLGA and folic acid (FoA). The PLGA-coated FoA-MSN exhibited a pH-dependent controlled release of the CAP (capecitabine) drug, showing efficient release at pH 6.8. Furthermore, the in vitro MTT test on PANC1 and MIAPaCa-2 resulted in an IC50 value of 146.37 µg/ml and 105.90 µg/ml, respectively. Mitochondrial-mediated apoptosis was confirmed from the caspase-3 and annexin V/PI flow cytometry assay, which displayed a cell cycle arrest at the G1 phase. Overall, the results predicted that the designed nanoformulation is a potential therapeutic agent in treating pancreatic cancer.

Outcomes with allogeneic hematopoietic stem cell transplantation in TP53-mutated myelodysplastic syndrome: A systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated myelodysplastic syndromes (MDS). A literature search was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov. After screening 626 articles, eight studies were included. Data were extracted following the PRISMA guidelines and analyzed using the meta-package by Schwarzer et al. We analyzed 540 patients. The pooled median 3 (1-5) year overall survival was 21% (95% CI 0.08-0.37, I2=91%, n=540). The pooled relapse rate was 58.9% (95% CI 0.38-0.77, I2=93%, n=487) at a median of 1.75 (1-3) years. The pooled 4-year progression- free survival was 34.8% (95% CI 0.15-0.57, I2=72%, n=105). Outcomes of Allo-HSCT for TP53-mutated MDS patients remain poor, with 21% OS at three years; however, Allo-HSCT confers a survival advantage as compared to non-transplant palliative therapies. Our findings suggest the need to explore novel therapeutic agents in prospective clinical trials.

Kidney Failure Risk Equation in vascular access planning: a population-based study supporting value in decision making.

Background: The Kidney Failure Risk Equation (KFRE) can play a better role in vascular access (VA) planning in patients with chronic kidney disease (CKD) requiring hemodialysis (HD). We described the VA creation and utilization pattern under existing estimated glomerular filtration rate (eGFR)-based referral, and investigated the utility of KFRE score as an adjunct variable in VA planning. Methods: Patients with CKD aged ≥18 years with eGFR <20 mL/min/1.73 m2 who chose HD as dialysis modality from January 2010 to August 2020 were included from a population-based database in British Columbia, Canada. Modality selection date was the index date. Exposures were categorized as (i) current eGFR-based referral, (ii) eGFR-based referral plus KRFE 2-year risk score on index date (KFRE-2) >40% and (iii) eGFR-based referral plus KFRE-2 ≤40%. We estimated the proportion of patients who started HD on arteriovenous fistula/graft (AVF/G) within 2 years, indicating timely pre-emptive creation, and the proportion of patients in whom AVF/G was created but did not start HD within 2 years, indicating too-early creation. Results: Study included 2581 patients, median age 71 years, 60% male. Overall, 1562(61%) started HD and 276 (11%) experienced death before HD initiation within 2 years. Compared with current referral, the proportion of patients who started HD on AVF/G was significantly higher when KFRE-2 was considered in addition to current referral (49% vs 58%, P-value <.001). Adjunct KFRE-2 significantly reduced too-early creation (31% vs 18%, P-value <.001). Conclusions: KFRE in addition to existing eGFR-based referral for VA creation has the potential to improve VA resource utilization by ensuring more patients start HD on AVF/G and may minimize too-early/unnecessary creation. Prospective research is necessary to validate these findings.

Development and optimization of oleogel made with soy protein isolate and xanthan gum using emulsion template approach and its comparison with solid fats.

This study aims to develop oleogel as a potential substitute for solid fats in the diet. A novel combination of unmodified Soy Protein Isolate (SPI) and Xanthan Gum (XG) have been utilized to gelate sunflower oil, using an emulsion template approach. The experimental trials employing Response Surface Methodology are conducted to optimize various parameters that affect the oil binding capacity, textural and rheological properties of the oleogel. The concentration of soy protein varies in the range of 5-15 %, the ratio of soy protein to xanthan gum ranges from 1:2 to 1:4, and the ionic strength varies from 0.2 to 1 M. The goal is to formulate oleogel that closely resembles solid fats. Responses namely the oil binding capacity and gel strength value of oleogel were observed best fitted to a linear model whereas, the hardness of oleogel found following a quadratic model. The SPI-XG combination was found effective in entraping more than 95 % of the oil. The best formulation of SPI: XG, 1:4; SPI concentration, 15 % and ionic strength of 1.0 M with 95.5 % of oil retention and hardness and gel strength value comparable to commercial solid fats.

Laparoscopic versus robotic cholecystectomy: a systematic review with meta-analysis to differentiate between postoperative outcomes and cost-effectiveness.

Background: Robotic cholecystectomy (RC) has shown promising outcomes in multiple studies when compared with the gold standard laparoscopic cholecystectomy (LC). The objective of this study is to compare the postoperative surgical outcomes and cost in patients undergoing RC versus LC. Methods: Studies reporting postoperative outcomes and costs in patients undergoing RC versus LC were selected from medical electronic databases and analysis was conducted by the values of systematic review on the statistical software RevMan version 5. Results: Six trials on 1,013 affected individuals for post-operative outcomes and cost comparison were used. Random effect model analysis was used in the analysis. Duration of operation (mean difference: -10.23, 95% CI: -16.23 to -4.22, Z=3.34, P=0.0008) was shorter in the LC group with moderate heterogeneity. Bile leak (odds ratio: 3.34, 95% CI: 0.85 to 13.03, Z=1.73, P=0.08) and no heterogeneity was seen, Postoperative complications (odds ratio: 1.49, 95% CI: 0.50 to 4.46, Z=0.72, P=0.47) with moderate heterogeneity. Both were statistically similar. LC had reduced cost (standardised mean difference: -7.42, 95% CI: -13.10 to -1.74, Z=2.56, P=0.01) with significant heterogeneity. Conclusions: RC failed to prove any clinical advantage over LC for postoperative outcomes including longer duration of operation moreover LC was more cost effective. Due to the paucity of randomised control trial (RCT) and significant heterogeneity, a major multicentre RCT is required to strengthen and validate the findings.

Differences between Survival Rates and Patterns of Failure of Patients with Lung Adenocarcinoma and Squamous Cell Carcinoma Who Received Single-Fraction Stereotactic Body Radiotherapy.

We investigated the survival and patterns of failure in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) in early stage non-small cell lung cancer (NSCLC) treated with single-fraction stereotactic body radiation therapy (SF-SBRT) of 27-34 Gray. A single-institution retrospective review of patients with biopsy-proven early stage ADC or SCC undergoing definitive SF-SBRT between September 2008 and February 2023 was performed. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes included local failure (LF), nodal failure (NF), and distant failure (DF). Of 292 eligible patients 174 had adenocarcinoma and 118 had squamous cell carcinoma. There was no significant change in any outcome except distant failure. Patients with ADC were significantly more likely to experience distant failure than patients with SCC (p = 0.0081). In conclusion, while SF-SBRT produced similar LF, NF, DFS, and OS, the higher rate of distant failure in ADC patients suggests that ongoing trials of SBRT and systemic therapy combinations should report their outcomes by histology.