Category: Nevin Manimala

Int J Surg. 2023 May 29. doi: 10.1097/JS9.0000000000000496. Online ahead of print.

ABSTRACT

OBJECTIVE: Overall survival (OS) is the gold-standard outcome measure for phase 3 trials, but the need for long follow-up period can delay the translation of potentially effective treatment to clinical practice. The validity of Major Pathological Response (MPR) as a surrogate of survival for non small cell lung cancer (NSCLC) after neoadjuvant immunotherapy remains unclear.

METHODS: Eligibility was resectable stage I-III NSCLC and delivery of PD-1/PD-L1/CTLA-4 inhibitors prior to resection; other forms/modalities of neoadjuvant and/or adjuvant therapies were allowed. Statistics utilized the Mantel-Haenszel fixed-effect or random-effect model depending on the heterogeneity (I2).

RESULTS: Fifty-three trials (7 randomized, 29 prospective nonrandomized, 17 retrospective) were identified. The pooled rate of MPR was 53.8%. Compared to neoadjuvant chemotherapy, neoadjuvant chemo-immunotherapy achieved higher MPR (OR 6.19, 4.39-8.74, P<0.00001). MPR was associated with improved DFS/PFS/EFS (HR 0.28, 0.10-0.79, P=0.02) and OS (HR 0.80, 0.72-0.88, P＜0.0001). Patients with stage III (vs I/II) and PD-L1 ≥1% (vs <1%) more likely achieved MPR (OR 1.66,1.02-2.70, P=0.04; OR 2.21,1.28-3.82, P=0.004).

CONCLUSIONS: The findings of this meta-analysis suggest that neoadjuvant chemo-immunotherapy achieved higher MPR in NSCLC patients，and increased MPR might be associated with survival benefits treated with neoadjuvant immunotherapy. It appears that the MPR may serve as a surrogate endpoint of survival to evaluate neoadjuvant immunotherapy.

PMID:37247009 | DOI:10.1097/JS9.0000000000000496

Int J Surg. 2023 May 29. doi: 10.1097/JS9.0000000000000494. Online ahead of print.

ABSTRACT

BACKGROUND: The rural-urban disparities in postoperative complications and costs among patients undergoing knee arthroplasty (KA) have not been thoroughly explored. This study aimed to determine whether such differences exist in this patient population.

MATERIAL AND METHODS: The study was conducted using data from the national Hospital Quality Monitoring System of China. Hospitalized patients undergoing KA from 2013 to 2019 were enrolled. Patient and hospital characteristics were compared between rural and urban patients, and differences in postoperative complications, readmissions, and hospitalization costs were analyzed using propensity score matching.

RESULTS: Of the 146,877 KA cases analyzed, 71.4% (104,920) were urban patients and 28.6% (41,957) were rural patients. Rural patients tended to be younger (64.4±7.7 y vs. 68.0±8.0 y; P<0.001) and had fewer comorbidities. In the matched cohort of 36,482 participants per group, rural patients were found to be more likely to experience deep vein thrombosis (OR: 1.31, 95% CI: 1.17-1.46; P<0.001) and require RBC transfusion (OR: 1.38, 95% CI: 1.31-1.46; P<0.001). However, they had a lower incidence of readmission within 30 days (OR: 0.65, 95% CI: 0.59-0.72; P<0.001) and readmission within 90 days (OR: 0.61, 95% CI: 0.57-0.66; P<0.001) than their urban counterparts. In addition, rural patients incurred lower hospitalization costs than urban patients (57,396.2 Chinese Yuan [CNY] vs. 60,844.3 CNY; P<0.001).

CONCLUSION: Rural KA patients had different clinical characteristics compared with urban patients. While they had a higher likelihood of deep vein thrombosis and RBC transfusion following KA than urban patients, they had fewer readmissions and lower hospitalization costs. Targeted clinical management strategies are needed for rural patients.

PMID:37247007 | DOI:10.1097/JS9.0000000000000494

Graefes Arch Clin Exp Ophthalmol. 2023 May 29. doi: 10.1007/s00417-023-06119-9. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the outcomes of micropulse transscleral laser therapy (MP-TLT) in patients with uncontrolled glaucoma and prior glaucoma aqueous tube shunt.

METHODS: In this single‑center, retrospective, interventional case series, eyes that underwent MP-TLT and had prior glaucoma aqueous tube shunt surgeries were included. The Cyclo Glaucoma Laser System (IRIDEX Corporation, Mountain View, CA, USA) with the MicroPulse P3 probe (version 1) was used. Post‑operative data were collected at day 1, week 1, and months 1, 3, 6, 12, 18, 24, 30 and 36.

RESULTS: A total of 84 eyes (84 patients) with mean age of 65.8 ± 15.2 years and with advanced glaucoma (baseline mean deviation -16.25 ± 6.80 dB and best-corrected visual acuity 0.82 ± 0.83 logMar) were included in the study. Baseline mean IOP was 19.95 ± 5.6 mm Hg with a mean number of medications 3.39 ± 1.02. There were statistically significant differences in IOP between baseline and all follow-up visits (p < 0.01 for all). The mean percentage of IOP reduction between baseline and different follow-up visits ranged from 23.4% to 35.5% (p < 0.01). There was a significant reduction of visual acuity (≥ 2-lines) at 1 year (30.3%) and 2 years (76.78%). There was a statistically significant reduction in the number of glaucoma medications between baseline and all follow-up visits after postoperative week 1 (p < 0.05 for all). No severe complications including persistent hypotony and related complications were observed. At the last follow-up visit, only 24 (28%) eyes out of 84 eyes remained in the study.

CONCLUSION: MP-TLT is an effective treatment for reducing IOP and decreasing the number of medications in patients with advanced glaucoma and prior glaucoma aqueous tube shunt.

PMID:37247002 | DOI:10.1007/s00417-023-06119-9

Abdom Radiol (NY). 2023 May 29. doi: 10.1007/s00261-023-03964-4. Online ahead of print.

ABSTRACT

PURPOSE: To assess inter-observer agreement and accuracy of LI-RADS v2018 for differentiating tumor in vein (TIV) from bland thrombus on gadoxetic acid-enhanced magnetic resonance imaging (Gx-MRI). Secondarily, to determine whether a multi-feature model improves accuracy compared to LI-RADS.

METHODS: We retrospectively identified consecutive patients at risk for hepatocellular carcinoma with venous occlusion(s) reported on Gx-MRI. Five radiologists independently classified each occlusion as TIV or bland thrombus using the LI-RADS TIV criterion (enhancing soft tissue in vein). They also evaluated imaging features suggestive of TIV or bland thrombus. Intra-class correlation coefficient (ICC) was calculated for individual features. A multi-feature model was developed based on consensus scores of features with > 5% consensus prevalence and > 0.40 ICC. Sensitivity and specificity of the LI-RADS criterion and of the cross-validated multi-feature model were compared.

RESULTS: Ninety-eight patients with 103 venous occlusions (58 TIV, 45 bland thrombus) were included. The LI-RADS criterion provided 0.63 ICC and, depending on the reader, 0.62-0.93 sensitivity and 0.87-1.00 specificity. Five other features had > 5% consensus prevalence and > 0.40 ICC, including three LI-RADS suggestive features and two non-LI-RADS features. The optimal multi-feature model incorporated the LI-RADS criterion and one LI-RADS suggestive feature (occluded or obscured vein contiguous with malignant parenchymal mass). After cross-validation, the multi-feature model did not improve sensitivity or specificity compared to the LI-RADS criterion (P = 0.23 and 0.25, respectively).

CONCLUSION: Using Gx-MRI, the LI-RADS criterion for TIV provides substantial inter-observer agreement, variable sensitivity, and high specificity for differentiating TIV from bland thrombus. A cross-validated multi-feature model did not improve diagnostic performance.

PMID:37246973 | DOI:10.1007/s00261-023-03964-4

Vet Ophthalmol. 2023 May 29. doi: 10.1111/vop.13108. Online ahead of print.

ABSTRACT

BACKGROUND: The ocular side effects of cancer chemotherapeutic drugs are relatively uncommon. Nonetheless, the ocular system has a potentially high sensitivity to toxic substances. This study proposed a framework to assess the effect of vincristine chemotherapy on intraocular pressure, tear protein, and oxidative stress in canines with transmissible venereal tumor (TVT).

METHODS: The study group comprised 10 dogs with TVT, whose diagnosis was based on cytology, and all dogs were treated with vincristine for 4 weeks. Each animal was given a complete ophthalmic examination, followed by a standard Schirmer tear test. Before and 20 min after administering vincristine, intraocular pressure (IOP) was measured in the eyes with a noncontact tonometer. At any of the times mentioned, tear samples were collected using the Schirmer test procedure and were subjected to protein analysis-oxidative stress index (OSI), total antioxidant capacity (TAC), total oxidant status (TOS), nitric oxide (NO), and malondialdehyde (MDA) were determined, and standard statistical analysis was applied.

RESULTS: No significant differences were found in protein in tears, but mean Pre and Postinjection IOP revealed a significant decrease in the eyes each week. Also, results indicated significant differences in oxidative stress markers: increased OSI, NO, and MDA, and reduced TAC.

CONCLUSION: The importance of an increase in oxidative stress levels in the tears of vincristine-treated patients should be taken seriously, as it appears to play a role in the pathogenesis of eye disease. Therefore, during the treatment weeks prior to prescribing vincristine, eye diseases should be evaluated and considered.

PMID:37246963 | DOI:10.1111/vop.13108

JBI Evid Synth. 2023 May 29. doi: 10.11124/JBIES-22-00349. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this systematic review is to investigate oncological and functional outcomes following primary transoral surgery compared with non-surgical management in patients with small-volume (T1-2, N0-2) oropharyngeal cancer.

INTRODUCTION: The incidence of oropharyngeal cancer is rising. Transoral surgery was introduced to provide a minimally invasive treatment option for patients with small-volume oropharyngeal cancer and to avoid the morbidity that results from open surgery and the potential acute and late toxicities of chemoradiotherapy.

INCLUSION CRITERIA: The review will include all studies on adult patients with small-volume oropharyngeal cancer managed by transoral surgery or non-surgical management with radiotherapy and/or chemotherapy. All patients must have undergone treatment with curative intent. Participants who underwent palliative treatment will be excluded.

METHODS: This review will follow the JBI methodology for systematic reviews of effectiveness. Eligible study designs will include randomized controlled trials, quasi-experimental studies, and prospective or retrospective cohort studies. Databases to be searched will include PubMed, Embase, CINAHL, Cochrane CENTRAL, and multiple trial registries from 1972. Titles and abstracts will be reviewed, and full-text articles will be retrieved if they meet the inclusion criteria. All eligible studies will be critically appraised by 2 independent reviewers using the appropriate JBI tools for experimental and observational designs. Where possible, outcome data from studies will be pooled with statistical meta-analysis to compare both oncological and functional outcomes between the two groups. All time to event to data will be converted to a common metric for oncological outcomes. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach will be followed to assess the certainty of findings.

SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 352509.

PMID:37246954 | DOI:10.11124/JBIES-22-00349

J Chem Theory Comput. 2023 May 29. doi: 10.1021/acs.jctc.3c00020. Online ahead of print.

ABSTRACT

We subject a series of five protein-ligand systems which contain important SARS-CoV-2 targets, 3-chymotrypsin-like protease (3CLPro), papain-like protease, and adenosine ribose phosphatase, to long time scale and adaptive sampling molecular dynamics simulations. By performing ensembles of ten or twelve 10 μs simulations for each system, we accurately and reproducibly determine ligand binding sites, both crystallographically resolved and otherwise, thereby discovering binding sites that can be exploited for drug discovery. We also report robust, ensemble-based observation of conformational changes that occur at the main binding site of 3CLPro due to the presence of another ligand at an allosteric binding site explaining the underlying cascade of events responsible for its inhibitory effect. Using our simulations, we have discovered a novel allosteric mechanism of inhibition for a ligand known to bind only at the substrate binding site. Due to the chaotic nature of molecular dynamics trajectories, regardless of their temporal duration individual trajectories do not allow for accurate or reproducible elucidation of macroscopic expectation values. Unprecedentedly at this time scale, we compare the statistical distribution of protein-ligand contact frequencies for these ten/twelve 10 μs trajectories and find that over 90% of trajectories have significantly different contact frequency distributions. Furthermore, using a direct binding free energy calculation protocol, we determine the ligand binding free energies for each of the identified sites using long time scale simulations. The free energies differ by 0.77 to 7.26 kcal/mol across individual trajectories depending on the binding site and the system. We show that, although this is the standard way such quantities are currently reported at long time scale, individual simulations do not yield reliable free energies. Ensembles of independent trajectories are necessary to overcome the aleatoric uncertainty in order to obtain statistically meaningful and reproducible results. Finally, we compare the application of different free energy methods to these systems and discuss their advantages and disadvantages. Our findings here are generally applicable to all molecular dynamics based applications and not confined to the free energy methods used in this study.

PMID:37246943 | DOI:10.1021/acs.jctc.3c00020

Mov Disord. 2023 May 29. doi: 10.1002/mds.29454. Online ahead of print.

ABSTRACT

BACKGROUND: Many children with tic disorders outgrow their tics, but little is known about the proportion of individuals who will continue to require specialist services in adulthood and which variables are associated with tic persistence.

OBJECTIVES: The aims were to estimate the proportion of individuals first diagnosed with tic disorders in childhood who continued to receive tic disorder diagnoses after age 18 years and to identify risk factors for persistence.

METHODS: In this Swedish nationwide cohort study including 3761 individuals diagnosed with tic disorders in childhood, we calculated the proportion of individuals whose diagnoses persisted into adulthood. Minimally adjusted logistic regression models examined the associations between sociodemographic, clinical, and family variables and tic disorder persistence. A multivariable model was then fitted, including only variables that were statistically significant in the minimally adjusted models.

RESULTS: Seven hundred and fifty-four (20%) children with tic disorders received a diagnosis of a chronic tic disorder in adulthood. Psychiatric comorbidity in childhood (particularly attention-deficit hyperactivity disorder, obsessive-compulsive disorder, pervasive developmental disorders, and anxiety disorders) and psychiatric disorders in first-degree relatives (particularly tic and anxiety disorders) were the strongest risk factors for persistence. We did not observe statistically significant associations with socioeconomic variables, perinatal complications, comorbid autoimmune diseases, or family history of autoimmune diseases. All statistically significant variables combined explained approximately 10% of the variance in tic disorder persistence (P < 0.0001).

CONCLUSIONS: Childhood psychiatric comorbidities and family history of psychiatric disorders were the strongest risk factors associated with tic disorder persistence into adulthood. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PMID:37246931 | DOI:10.1002/mds.29454

Neurogastroenterol Motil. 2023 May 29:e14614. doi: 10.1111/nmo.14614. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: The aim of the study was to evaluate the effect of an electronic positional therapy wearable device on nocturnal gastroesophageal reflux measured by pH-impedance reflux monitoring.

METHODS: We performed a single-center, prospective, interventional study in 30 patients with nocturnal reflux symptoms and a nocturnal esophageal acid exposure time (AET) ≥1.5% measured off acid-suppressive medication by ambulatory pH-impedance reflux monitoring. Patients were treated with an electronic positional therapy wearable device for 2 weeks. The device vibrates in the right lateral decubitus position so it conditions patients to avoid that sleep position. After 2 weeks treatment, the pH-impedance study was repeated. Primary outcome was the change in nocturnal AET. Secondary outcomes include change in number of reflux episodes and reflux symptoms.

RESULTS: Complete data were available for 27 patients (13 females, mean age 49.8 years). The median nocturnal AET decreased from 6.0% (IQR, 2.3-15.3) to 3.1% (0.1-10.8) after 2 weeks of treatment (p = 0.079). The number of reflux episodes was significantly reduced after 2 weeks of treatment (baseline: 8.0 (3.0-12.3) vs. end: 3.0 (1.0-8.0); p = 0.041). Treatment led to a statistically significant decrease in time spent in right lateral decubitus position (baseline: mean 36.9% ± 15.2% vs. end: 2.7% ± 8.2%; p = <0.001) and an increase in the left lateral decubitus position (baseline 29.2% ± 14.8% vs. end: 63.3% ± 21.9%; p = <0.001). Symptom improvement was reported by 70.4% of the patients.

CONCLUSIONS: Sleep positional therapy using an electronic wearable device promotes sleeping in the left lateral decubitus position and improves reflux parameters measured by pH-impedance reflux monitoring.

PMID:37246930 | DOI:10.1111/nmo.14614

Womens Health (Lond). 2023 Jan-Dec;19:17455057231175810. doi: 10.1177/17455057231175810.

ABSTRACT

BACKGROUND: As the awareness towards gender-specific therapies continues to increase among all fields of medicine, so does the need for gender-sensitive evaluations of established surgical techniques. With a higher likelihood of anterior cruciate ligament injury in women, a critical assessment of the functional outcome of anterior cruciate ligament reconstruction regarding patient sex is indispensable. Almost all pre-existing literature on this subject is based on anterior cruciate ligament reconstructions carried out before 2008, when ‘all-inside’ techniques did not exist. This implicates the need to investigate this technique towards its differences in outcome between male and female patients.

OBJECTIVES: The purpose of this study was to determine whether there is a difference concerning the functional outcome of an ‘all-inside’ technique for anterior cruciate ligament reconstruction in female patients when compared to a cohort of male patients matched for body mass index and age.

DESIGN: Retrospective analysis.

METHODS: All female patients who underwent anterior cruciate ligament reconstruction using an all-inside technique between 2011 and 2012 were examined for inclusion. Functional outcome parameters investigated included the Lysholm Knee Score, International Knee Documentation Committee score, Visual Analogue Scale score and the Tegner Activity Scale. All parameters were documented before surgery and at 3-, 6-, 12- and >24 months follow-up. At 24-month follow-up, anterior-posterior knee laxity was tested using the KT-2000 arthrometer device. For comparison, an equivalent group of male patients who underwent the same procedure was matched.

RESULTS: 27 female patients were matched with 27 male patients. The average age was 29 years, and a mean follow-up of 90 months could be achieved with 27 of patients reaching a follow-up of > 10 years. The evaluated scores showed no significant difference between female and male patients. Women presented with poorer functional outcome at 3- as well as 6-month follow-ups compared to men, without reaching statistical significance. After 12 months, no further differences could be found.

CONCLUSION: This study proved that an all-inside technique for anterior cruciate ligament reconstruction is able to produce the same functional outcome in female as in male patients at long-term follow-up. The results on short-term outcome indicate the need for further research towards gender-specific differences after anterior cruciate ligament reconstruction, their potential causes and potential of improvement.

LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID:37246602 | DOI:10.1177/17455057231175810