Nevin Manimala

J Small Anim Pract. 2024 Jul 12. doi: 10.1111/jsap.13763. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the complication rate, mortality rate and putative risk factors for cecal or colonic surgery in dogs.

MATERIALS AND METHODS: A multi-institutional retrospective study including dogs that had undergone surgery that involved the cecum or the colon. Medical records from three referral hospitals were reviewed for patient demographics and clinical data. The association between putative risk factors and survival to discharge or complications was assessed using univariable and multivariable analysis.

RESULTS: Seventy-nine dogs met the criteria to be included in this study. Fifty-five dogs had full thickness incision surgeries, while 24 dogs had partial thickness surgeries. The complication and mortality rates for full thickness and partial thickness cecal/colonic surgeries were not statistically different. The dehiscence rate of colonic anastomosis in this study was four of 47 (8.5%). On univariate analysis, performing full thickness procedures out of hours had an association with increased complications and mortality. On multivariable analysis, no factors were associated with survival to discharge or complications. There was no association of board-certified surgeon presence in surgery with complications or mortality.

CLINICAL SIGNIFICANCE: The performance of full thickness cecal/colonic surgery is not associated with a statistically significant increased risk for complications or mortality compared to partial thickness procedures, with a possible increased risk of complications and mortality in full thickness procedures out of hours.

PMID:39001633 | DOI:10.1111/jsap.13763

Aliment Pharmacol Ther. 2024 Jul 12. doi: 10.1111/apt.18149. Online ahead of print.

ABSTRACT

AIMS: We conducted a clinical trial to determine the efficacy of the combination of vitamin E and/or docosahexaenoic acid (DHA) versus placebo in reducing liver fat content after 6 months of intervention in adults with MASLD.

METHODS: Adults with MASLD were randomised to one of four treatment arms (vitamin E 1000 mg/daily + DHA 1.89 g/daily or combination arm, vitamin E 1000 mg alone, DHA 1.89 g alone or placebo) following a 2:1:1:2 randomisation. The primary objective was to determine the efficacy of DHA + vitamin E versus placebo in reducing hepatic fat fraction (%) relative to baseline after 6 months of intervention. Secondary objectives were to determine the effect of vitamin E or DHA alone versus placebo on reducing liver fat at 6 months.

RESULTS: Our cohort consisted of 203 subjects with a mean age of 51 years, 53% female, 91% White, 59% Hispanic ethnicity. The combination of vitamin E + DHA had no effect on the primary endpoint of reducing hepatic steatosis as determined by MRI-PDFF (p = 0.98). Neither vitamin E alone (p = 0.91) nor DHA alone (p = 0.14) significantly reduced hepatic steatosis compared to placebo. However, the trial was not powered adequately for this analysis. Compared with placebo, no statistically significant differences were detected in the 3-month or 6-month levels for ALT (U/L) or AST (U/L) in all three intervention groups.

CONCLUSIONS: The combination of DHA + vitamin E or either agent alone did not demonstrate efficacy on reducing liver fat or aminotransferases in the studied population.

PMID:39001559 | DOI:10.1111/apt.18149

J Biopharm Stat. 2024 Jul 12:1-10. doi: 10.1080/10543406.2024.2374850. Online ahead of print.

ABSTRACT

In this paper, we propose a new Bayesian adaptive design, score-goldilocks design, which has the same algorithmic idea as goldilocks design. The score-goldilocks design leads to a uniform formula for calculating the probability of trial success for different endpoint trials by using the normal approximation. The simulation results show that the score-goldilocks design is not only very similar to the goldilocks design in terms of operating characteristics such as type 1 error, power, average sample size, probability of stop for futility, and probability of early stop for success, but also greatly saves the calculation time and improves the operation efficiency.

PMID:39001557 | DOI:10.1080/10543406.2024.2374850

Cancers (Basel). 2024 Jul 8;16(13):2492. doi: 10.3390/cancers16132492.

ABSTRACT

BACKGROUND: This study aimed to estimate the relative efficacy of neoadjuvant nivolumab in combination with chemotherapy (neoNIVO + CT) compared to relevant treatments amongst resectable non-metastatic non-small-cell lung cancer (rNSCLC) patients.

METHODS: Treatment comparisons were based on a network meta-analysis (NMA) using randomized clinical trial data identified via systematic literature review (SLR). The outcomes of interest were event-free survival (EFS) and pathological complete response (pCR). NeoNIVO + CT was compared to neoadjuvant chemotherapy (neoCT), neoadjuvant chemoradiotherapy (neoCRT), adjuvant chemotherapy (adjCT), and surgery alone (S). Due to the potential for effect modification by stage, all-stage and stage-specific networks were considered. Fixed-effect (FE) and random-effects Bayesian NMA models were run (EFS = hazard ratios [HR]; pCR = odds ratios [OR]; 95% credible intervals [CrI]).

RESULTS: Sixty-one RCTs were identified (base case = 9 RCTs [n = 1978 patients]). In the all-stages FE model, neoNIVO + CT had statistically significant EFS improvements relative to neoCT (HR = 0.68 [95% CrI: 0.49, 0.94]), S (0.59 [0.42, 0.82]), adjCT (0.66 [0.45, 0.96]), but not relative to neoCRT (HR = 0.77 [0.52, 1.16]). NeoNIVO + CT (5 RCTs) had statistically significant higher odds of pCR relative to neoCT (OR = 12.53 [5.60, 33.82]) and neoCRT (7.15 [2.31, 24.34]). Stage-specific model findings were consistent.

CONCLUSIONS: This NMA signals improved EFS and/or pCR of neoNIVO + CT relative to comparators among patients with rNSCLC.

PMID:39001554 | DOI:10.3390/cancers16132492

Cancers (Basel). 2024 Jul 8;16(13):2488. doi: 10.3390/cancers16132488.

ABSTRACT

The development of cancer involves the accumulation of somatic mutations in several essential biological pathways. Delineating the temporal order of pathway mutations during tumorigenesis is crucial for comprehending the biological mechanisms underlying cancer development and identifying potential targets for therapeutic intervention. Several computational and statistical methods have been introduced for estimating the order of somatic mutations based on mutation profile data from a cohort of patients. However, one major issue of current methods is that they do not take into account intra-tumor heterogeneity (ITH), which limits their ability to accurately discern the order of pathway mutations. To address this problem, we propose PATOPAI, a probabilistic approach to estimate the temporal order of mutations at the pathway level by incorporating ITH information as well as pathway and functional annotation information of mutations. PATOPAI uses a maximum likelihood approach to estimate the probability of pathway mutational events occurring in a specific sequence, wherein it focuses on the orders that are consistent with the phylogenetic structure of the tumors. Applications to whole exome sequencing data from The Cancer Genome Atlas (TCGA) illustrate our method’s ability to recover the temporal order of pathway mutations in several cancer types.

PMID:39001551 | DOI:10.3390/cancers16132488

Cancers (Basel). 2024 Jul 7;16(13):2477. doi: 10.3390/cancers16132477.

ABSTRACT

Minimally invasive surgery has provided several clinical advantages in locally advanced gastric cancer (LAGC) care, although a consensus on its application criteria remains unclear. Surgery remains a careful choice in elderly patients, who frequently present with frailty, comorbidities, and other disabling diseases. This study aims to assess the possible advantages of laparoscopic gastric resections in elderly patients presenting with LAGC. This retrospective study analyzed a single-center series of elderly patients (≥75 years) undergoing curative resections for LAGC between 2015 and 2020. A comparative analysis of open versus laparoscopic approaches was conducted, focusing on postoperative complications, length of hospital stay (LOS), and long-term survival. A total of 62 patients underwent gastrectomy through an open or a laparoscopic approach (31 pts each). The study population did not show statistically significant differences in demographics, operative risk, and neoadjuvant chemotherapy. The laparoscopic group reported significantly minimized overall complications (45.2 vs. 71%, p = 0.039) and pulmonary complications (0 vs. 9.7%, p = 0.038) as well as a shorter LOS (8 vs. 12 days, p = 0.007). Lymph node harvest was equal between the groups, although long-term overall survival presented significantly better after laparoscopic gastrectomy (p = 0.048), without a relevant difference in terms of disease-free and disease-specific survivals. Laparoscopic gastrectomy proves effective in elderly LAGC patients, offering substantial short- and long-term postoperative benefits.

PMID:39001540 | DOI:10.3390/cancers16132477

Cancers (Basel). 2024 Jul 6;16(13):2471. doi: 10.3390/cancers16132471.

ABSTRACT

Colorectal cancer (CRC) represents a substantial burden on global healthcare, contributing to significant morbidity and mortality worldwide. Despite advances in screening methodologies, its incidence remains high, necessitating continued efforts in early detection and treatment. Neoplastic invasion and metastasis are primary determinants of CRC lethality, emphasizing the urgency of understanding underlying mechanisms to develop effective therapeutic strategies. This study aimed to explore the potential of serum biomarkers in predicting survival outcomes in CRC patients, with a focus on cathepsin B (CB), leukocytic elastase (LE), total sialic acid (TSA), lipid-associated sialic acid (LASA), antitrypsin activity (ATA), C-reactive protein (CRP), and cystatin C (CC). We recruited 185 CRC patients and 35 healthy controls, assessing demographic variables, tumor characteristics, and 7 serum biomarker levels, including (1) CB, (2) LE, (3) TSA, (4) LASA, (5) ATA, (6) CRP, and (7) CC. Statistical analyses included ANOVA with Tukey’s post hoc tests and MANOVA for continuous variables. Student’s t-test was used for dependent samples, while non-parametric tests like Mann-Whitney U and Wilcoxon signed-rank tests were applied for variables deviating from the normal distribution. Categorical variables were assessed using chi-square and Kruskal-Wallis tests. Spearman’s rank correlation coefficient was utilized to examine variable correlations. Survival analysis employed the Kaplan-Meier method with a log-rank test for comparing survival times between groups. Significant associations were observed between CB (p = 0.04), LE (p = 0.01), and TSA (p = 0.008) levels and survival outcomes in CRC patients. Dukes’ classification stages also showed a significant correlation with survival (p = 0.001). However, no significant associations were found for LASA, ATA, CRP, and CC. Multivariate analysis of LE, TSA, and ATA demonstrated a notable correlation with survival (p = 0.041), notwithstanding ATA’s lack of significance in univariate analysis (p = 0.13). CB, LE, and TSA emerged as promising diagnostic markers with prognostic value in CRC, potentially aiding in early diagnosis and treatment planning. Further research is needed to validate these findings and explore additional prognostic indicators.

PMID:39001534 | DOI:10.3390/cancers16132471

Cancers (Basel). 2024 Jul 4;16(13):2454. doi: 10.3390/cancers16132454.

ABSTRACT

The paper describes the statistical analysis of the response of gastric cancer cells and normal cells to broadband terahertz radiation up to 4 THz, both with and without the use of nanostructured contrast agents. The THz spectroscopy analysis was comparatively performed under the ATR procedure and transmission measurement procedure. The statistical analysis was conducted towards multiple pairwise comparisons, including a support medium (without cells) versus a support medium with nanoparticles, normal cells versus normal cells with nanoparticles, and, respectively, tumor cells versus tumor cells with nanoparticles. When generally comparing the ATR procedure and transmission measurement procedure for a broader frequency domain, the differentiation between normal and tumor cells in the presence of contrast agents is superior when using the ATR procedure. THz contrast enhancement by using contrast agents derived from MRI-related contrast agents leads to only limited benefits and only for narrow THz frequency ranges, a disadvantage for THz medical imaging.

PMID:39001516 | DOI:10.3390/cancers16132454

Cancers (Basel). 2024 Jul 2;16(13):2440. doi: 10.3390/cancers16132440.

ABSTRACT

OBJECTIVES: Glioblastomas (GBM) are the most common primary invasive neoplasms of the brain. Distinguishing between lesion recurrence and different types of treatment related changes in patients with GBM remains challenging using conventional MRI imaging techniques. Therefore, accurate and precise differentiation between true progression or pseudoresponse is crucial in deciding on the appropriate course of treatment. This retrospective study investigated the potential of apparent diffusion coefficient (ADC) map values derived from diffusion-weighted imaging (DWI) as a noninvasive method to increase diagnostic accuracy in treatment response.

METHODS: A cohort of 21 glioblastoma patients (mean age: 59.2 ± 11.8, 12 Male, 9 Female) that underwent treatment with bevacizumab were selected. The ADC values were calculated from the DWI images obtained from a standardized brain protocol across 1.5-T and 3-T MRI scanners. Ratios were calculated for rADC values. Lesions were classified as bevacizumab-induced cytotoxicity based on characteristic imaging features (well-defined regions of restricted diffusion with persistent diffusion restriction over the course of weeks without tissue volume loss and absence of contrast enhancement). The rADC value was compared to these values in radiation necrosis and recurrent lesions, which were concluded in our prior study. The nonparametric Wilcoxon signed rank test with p < 0.05 was used for significance.

RESULTS: The mean ± SD age of the selected patients was 59.2 ± 11.8. ADC values and corresponding mean rADC values for bevacizumab-induced cytotoxicity were 248.1 ± 67.2 and 0.39 ± 0.10, respectively. These results were compared to the ADC values and corresponding mean rADC values of tumor progression and radiation necrosis. Significant differences between rADC values were observed in all three groups (p < 0.001). Bevacizumab-induced cytotoxicity had statistically significant lower ADC values compared to both tumor recurrence and radiation necrosis.

CONCLUSION: The study demonstrates the potential of ADC values as noninvasive imaging biomarkers for differentiating recurrent glioblastoma from radiation necrosis and bevacizumab-induced cytotoxicity.

PMID:39001500 | DOI:10.3390/cancers16132440

J Neurosurg. 2024 Jul 12:1-7. doi: 10.3171/2024.4.JNS24256. Online ahead of print.

ABSTRACT

OBJECTIVE: Previous studies of neurosurgical transfers indicate that substantial numbers of patients may not need to be transferred, suggesting an opportunity to provide more patient-centered care by treating patients in their communities, while probably saving thousands of dollars in transport and duplicative workup. This study of neurosurgical transfers, the largest to date, aimed to better characterize how often transfers were potentially avoidable and which patient factors might affect whether transfer is needed.

METHODS: This was a retrospective cohort study of neurosurgical transfers to an urban, tertiary-care, level I trauma center between October 1, 2017, and October 1, 2022. Prior to data analysis, the authors devised criteria to differentiate necessary neurosurgical transfers from potentially avoidable ones. A transfer was considered necessary if 1) the patient went to the operating room within 12 hours of arrival at the emergency department (ED); 2) a neurological MRI study was conducted in the ED; 3) the patient was admitted to the ICU from the ED; or 4) the patient was admitted to either neurology or a surgical service (including neurosurgery). Transfers not meeting any of the above criteria were deemed potentially avoidable. Patient and clinical characteristics, including diagnostic groupings from Clinical Classification Software categories, were collected retrospectively via electronic health record data abstraction and stratified by whether the transfer was necessary or potentially avoidable. Statistical differences were assessed with a chi-square test.

RESULTS: A total of 5113 neurosurgical transfers were included in the study, of which 1701 (33.3%) were classified as potentially avoidable. Four percent of all transferred patients went to the operating room within 12 hours of reaching the receiving ED, 23.4% were admitted to the ICU from the ED, 26.6% had a neurological MRI study performed in the ED, and 54.4% were admitted to a surgical service or to neurology. Potentially avoidable transfers had a higher proportion of traumatic brain injury, headache, and syncope (p < 0.0001), as well as of spondylopathies/spondyloarthropathies (p = 0.0402), whereas patients needing transfer had a higher proportion of acute hemorrhagic cerebrovascular disease and cerebral infarction (p < 0.0001).

CONCLUSIONS: This study demonstrates that a large number of neurosurgical transfers can probably be treated in their home hospitals and highlights that the vast majority of patients transferred for neurosurgical conditions do not receive emergency neurosurgery. Further research is needed to better guide transferring and receiving facilities in reducing the burden of excessive transfers.

PMID:38996404 | DOI:10.3171/2024.4.JNS24256