Nevin Manimala

Iran Biomed J. 2023 Sep 3. doi: 10.61186/ibj.3845. Online ahead of print.

ABSTRACT

BACKGROUND: Non-small cell lung cancer accounts for 85% of tumors of the lung and is a leading cause of cancer mortality worldwide. MiR-34a and miR-126 mainly act as tumor suppressors and are often downregulated in various cancers, including NSCLC.

METHODS: The current study included 63 paraffin-embedded NSCLC and paired adjacent normal tissues. After DNA extraction and bisulfite treatment, the methylation status of miR-34a and miR-126 were evaluated using the MSP method.

RESULTS: There was no statistically significant difference between tumor and normal tissues regarding the methylation status of miR-34a and miR-126 (p > 0.05). Moreover, we found no significant correlation between the methylation status of miR-34a and miR-126 with patients’ demographic parameters, including gender, age, and pathology subtype (p > 0.05).

CONCLUSION: Considering the low expression of mir-126 and mir-34 in NSCLC, more sensitive methods are recommended to be exploited for detecting the level of methylation or underlying mechanisms other than promoter hypermethylation in silencing these genes in NSCLC.

PMID:38445462 | DOI:10.61186/ibj.3845

Int J Surg. 2024 Mar 4. doi: 10.1097/JS9.0000000000001149. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Besides the increased risk of perioperative morbidity, graft failure, and mortality, the majority of PVT are diagnosed at liver transplantation (LT). Improving preoperative management and patient selection may lead to better short-term and long-term outcomes and reduce the risk of a futile LT. The authors aimed to identify predictors of adverse outcomes after LT in patients with nonmalignant portal vein thrombosis (PVT) and improve donor to recipient matching by analyzing the results of the Italian cohort of LT recipients.

METHODS: Adult patients who underwent LT in Italy between January 2000 and February 2020 diagnosed with PVT pre-LT or at time of LT were considered eligible for inclusion. Based on a survey encompassing all 26 surgeons participating in the study, a binary composite outcome was defined. Patients were classified as having the composite event if at least one of these conditions occurred: operative time more than 600 min, estimated blood loss greater than 5000 ml, more than 20 ICU days, 90 days mortality, 90 days retransplant.

RESULTS: Seven hundred fourteen patients were screened and 698 met the inclusion criteria. The analysis reports the results of 568 patients that fulfilled the criteria to enter the composite outcome analysis.Overall, 156 patients (27.5%) developed the composite outcome. PVT stage 3/4 at transplant and need for any surgical correction of PVT are independent predictors of the composite outcome occurrence. When stratified by PVT grade, overall survival at 1-year ranges from 89.0% with PVT grade 0/1 to 67.4% in patients with PVT grade 3/4 at LT (P<0.001). Nevertheless, patients with severe PVT can improve their survival when identified risk factors are not present.

CONCLUSIONS: Potential LT candidates affected by PVT have a benefit from LT that should be adequately balanced on liver function and type of inflow reconstruction needed to mitigate the incidence of adverse events. Nonetheless, the absence of specific risk factors may improve the outcomes even in patients with PVT grades 3-4.

PMID:38445440 | DOI:10.1097/JS9.0000000000001149

Br J Surg. 2024 Mar 2;111(3):znae049. doi: 10.1093/bjs/znae049.

ABSTRACT

BACKGROUND: Evidence for the routine use of robotic technology and its impact on short-term outcomes in colon cancer surgery is lacking. The aim of this study was to compare the surgically induced systemic stress response and clinical and patient-reported outcomes for patients undergoing robot-assisted or laparoscopic colon cancer surgery.

METHODS: In this double-blinded superiority RCT completed between August 2021 and March 2023, patients with stage 1-3 colon cancer were randomized in a 1 : 1 ratio to undergo either robot-assisted or laparoscopic colon cancer surgery. The primary outcome was changes in the systemic stress response, characterized by C-reactive protein expression in the first three postoperative days. Secondary outcomes were intraoperative and postoperative complications and patient-reported outcomes. The latter included quality of recovery-15 and pain intensity using a visual analogue scale.

RESULTS: In total, 128 patients were screened for potential inclusion in this study; 50 patients (25 in the robot-assisted group and 25 in the laparoscopic group) were included in the final follow-up and analysis. The postoperative C-reactive protein response was higher on the first postoperative day in the laparoscopic group (mean difference = 19.88 mg/l, 95% c.i. 3.89-35.86; P = 0.045). No statistically significant differences were noted for C-reactive protein expression on the second and third postoperative days.

CONCLUSION: Adopting robot-assisted surgery for stage 1-3 colon cancer is associated with a reduction in the surgical stress response.

REGISTRATION NUMBER: NCT04687384 (http://www.clinicaltrials.gov).

PMID:38445434 | DOI:10.1093/bjs/znae049

Nanoscale. 2024 Mar 6. doi: 10.1039/d3nr04907h. Online ahead of print.

ABSTRACT

Titania nanoparticles with a diameter of 8 nm underwent an anisotropic modification using apolar 6-bromohexylphosphonic acid and cationic polar N,N,N-trimethyl-6-phosphonohexan-1-aminium bromide. The Janus modification was achieved through a straightforward one-step Pickering emulsion approach using toluene-water mixtures. The resulting Janus particles were compared with isotropically and statistically modified titania particles, where either a single coupling agent is attached to the surface or both coupling agents are assembled over the surface randomly, respectively. The covalent binding of the phosphonic acids to the titania surface was confirmed by FTIR and ³¹P solid-state CP-MAS NMR analyses. The grafting density was assessed using TGA, elemental analysis, and ICP-MS, revealing grafting densities of 0.1 mmol g^-1 to 0.5 mmol g^-1 for the cationic coupling agent and 1.2 mmol g^-1 to 1.5 mmol g^-1 for the apolar coupling agent, respectively. ζ-Potential titration measurements of both pristine and modified particles revealed isoelectric points at pH 4.5 to 9.3, depending on the type of modification. The ability of the particles to stabilize Pickering emulsions was tested under various conditions, with statistically and Janus-modified particles demonstrating a significant increase in stabilization compared to their isotropically modified counterparts. Furthermore, Janus particles were deposited onto glass substrates by a simple layer-by-layer approach. Through the self-assembly of these Janus particles, the glass substrate’s properties could be tailored from hydrophilic to hydrophobic to hydrophilic, depending on the dipping cycle.

PMID:38445431 | DOI:10.1039/d3nr04907h

Ren Fail. 2024 Dec;46(1):2325640. doi: 10.1080/0886022X.2024.2325640. Epub 2024 Mar 6.

ABSTRACT

BACKGROUND: The severity and course of sepsis-associated acute kidney injury (SA-AKI) are correlated with the mortality rate. Early detection of SA-AKI subphenotypes might facilitate the rapid provision of individualized care.

PATIENTS AND METHODS: In this post-hoc analysis of a multicenter prospective study, we combined conventional kidney function variables with serial measurements of urine (tissue inhibitor of metalloproteinase-2 [TIMP-2])* (insulin-like growth factor-binding protein [IGFBP7]) at 0, 6, 12, and 24 h) and then using an unsupervised hierarchical clustering of principal components (HCPC) approach to identify different phenotypes of SA-AKI. We then compared the subphenotypes with regard to a composite outcome of in-hospital death or the initiation of renal replacement therapy (RRT).

RESULTS: We included 184 patients presenting SA-AKI within 6 h of the initiation of catecholamines. Three distinct subphenotypes were identified: subphenotype A (99 patients) was characterized by a normal urine output (UO), a low SCr and a low [TIMP-2]*[IGFBP7] level; subphenotype B (74 patients) was characterized by existing chronic kidney disease (CKD), a higher SCr, a low UO, and an intermediate [TIMP-2]*[IGFBP7] level; and subphenotype C was characterized by very low UO, a very high [TIMP-2]*[IGFBP7] level, and an intermediate SCr level. With subphenotype A as the reference, the adjusted hazard ratio (aHR) [95%CI] for the composite outcome was 3.77 [1.92-7.42] (p < 0.001) for subphenotype B and 4.80 [1.67-13.82] (p = 0.004) for subphenotype C.

CONCLUSIONS: Combining conventional kidney function variables with urine measurements of [TIMP-2]*[IGFBP7] might help to identify distinct SA-AKI subphenotypes with different short-term courses and survival rates.

PMID:38445412 | DOI:10.1080/0886022X.2024.2325640

Tunis Med. 2023 Aug-Sep;101(8-9):709-714.

ABSTRACT

INTRODUCTION: The worldwide obesity epidemic continues unabated. Obesity and its associated health risks are considered as the major causes of morbidity and mortality. Currently, bariatric surgery is the most effective treatment for people with severe obesity resulting in sustainable weight loss and a reduced risk for co-morbidities. Sleeve gastrectomy is the most common bariatric procedure undertaken in Tunisia.

AIM: we aim to evaluate the vitamin status of the obese patients before and after sleeve gastrectomy.

METHODS: Thirty obese patients undergoing sleeve gastrectomy, were recruited from Obesity unit. In this study. A biological assessment was performed pre-operatively and controlled 6 months following the sleeve gastrectomy including: calcemia, parathyroid hormone (PTH), albuminemia and dosage of vitamin D, vitamin B9 and vitamin B12.

RESULTS: Six months post sleeve gastrectomy, vitamin deficiencies were more prevalent: the mean level of vitamin B9, vitamin B12 and vitamin D respectively, has decreased from 5.03±3.28 ng / ml to 2.71±1.52 ng / ml, from 348.06±158.92 pg/ml to 264.62±119.77 pg/ml and from 17.18±11.45 ng/ml to 11.69±8.22 ng/ml, with a statistically significant difference (p=0.008, p=0.01 and p=0.012). Sleeve gastrectomy has proven to be an effective weight loss treatment. However, nutritional deficiencies have worsened during postoperative period.

CONCLUSION: This study highlights the importance of early identification, appropriate treatment and prophylactic micronutrient supplementation.

PMID:38445407

Future Oncol. 2024 Mar 6. doi: 10.2217/fon-2023-0952. Online ahead of print.

ABSTRACT

Aims: This retrospective study aims to identify a possible predictive role of KRAS mutations in non-small-cell lung cancer in response to first-line pembrolizumab, either as monotherapy or combined with chemotherapy. Methods: Patients received pembrolizumab alone (n = 213) or associated with chemotherapy (n = 81). Results: A mutation in the KRAS gene was detected in 27% of patients. In patients on pembrolizumab alone, median progression-free survival in KRAS-mutated cases was longer than in wild-type cases (11.3 vs 4.4 months; p = 0.019), whereas median overall survival did not reach statistical significance (22.1 vs 12.5 months; p = 0.119). Patients receiving chemo-immunotherapy with KRAS-positive tumors had a similar progression-free survival (9.7 vs 7.3 months; p = 0.435); overall survival data were immature. Conclusion: This study suggests a correlation between KRAS status and response to pembrolizumab.

PMID:38445372 | DOI:10.2217/fon-2023-0952

Chin Med J (Engl). 2024 Mar 6. doi: 10.1097/CM9.0000000000002982. Online ahead of print.

ABSTRACT

BACKGROUND: Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys.

METHODS: This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models.

RESULTS: A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower (P = 0.008), while the cumulative progression rate was higher (P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys (P = 0.004) in the multivariable analysis.

CONCLUSION: The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

PMID:38445358 | DOI:10.1097/CM9.0000000000002982

Stat Methods Med Res. 2024 Mar 6:9622802241233768. doi: 10.1177/09622802241233768. Online ahead of print.

ABSTRACT

The performance of individual biomarkers in discriminating between two groups, typically the healthy and the diseased, may be limited. Thus, there is interest in developing statistical methodologies for biomarker combinations with the aim of improving upon the individual discriminatory performance. There is extensive literature referring to biomarker combinations under the two-class setting. However, the corresponding literature under a three-class setting is limited. In our study, we provide parametric and nonparametric methods that allow investigators to optimally combine biomarkers that seek to discriminate between three classes by minimizing the Euclidean distance from the receiver operating characteristic surface to the perfection corner. Using this Euclidean distance as the objective function allows for estimation of the optimal combination coefficients along with the optimal cutoff values for the combined score. An advantage of the proposed methods is that they can accommodate biomarker data from all three groups simultaneously, as opposed to a pairwise analysis such as the one implied by the three-class Youden index. We illustrate that the derived true classification rates exhibit narrower confidence intervals than those derived from the Youden-based approach under a parametric, flexible parametric, and nonparametric kernel-based framework. We evaluate our approaches through extensive simulations and apply them to real data sets that refer to liver cancer patients.

PMID:38445348 | DOI:10.1177/09622802241233768

Dan Med J. 2024 Feb 8;71(3):A08230526. doi: 10.61409/A08230526.

ABSTRACT

INTRODUCTION: Tendinopathy and tendon tears of the gluteus medius and/or minimus (GMM) insertion at the greater trochanter are increasingly recognised internationally as a cause of recalcitrant lateral hip pain (LHP). The purpose of this study was to report the first Danish results of open surgical repair of GMM tears in female patients.

METHODS: In this retrospective observational study, we included 67 women (68 hips) with a mean (95% confidence interval (CI)) age of 59 (56-61) years who underwent open GMM repair between September 2018 and June 2022. All cases had magnetic resonance imaging before surgery. Pre-, three- and 12-month post-operative testing included LHP (numerical rating scale 0-10), Copenhagen Hip and Groin Outcome Score (HAGOS), Oxford Hip Score (OHS), the EuroQol-Visual Analogue Scale (EQ-VAS) and the Global Rating of Change score (GROC). Responses on GROC were considered successful if patients scored “moderately better” to “very much better”. Function of the lower limbs was assessed by the 30-second Chair-Stand-Test (CST).

RESULTS: From pre-testing to 12-month follow-up, LHP at rest and during activity decreased significantly, all HAGOS subgroups improved by 27-35 points, the OHS improved from 22 to 35 points, the EQ-VAS improved from 52 to 72 points and the mean (95% CI) number of repetitions in the CST improved by 2.4 (1.4-3.3). Success on the GROC was reported by 79% of the patients.

CONCLUSION: Open surgical repair of GMM tendon tears in women produced statistically significant improvements in patient-reported outcomes at one-year follow-up.

FUNDING: None.

TRIAL REGISTRATION: Not relevant.

PMID:38445316 | DOI:10.61409/A08230526