Nevin Manimala

NPJ Precis Oncol. 2021 Jul 23;5(1):71. doi: 10.1038/s41698-021-00209-9.

ABSTRACT

The FDA recently approved eight targeted therapies for acute myeloid leukemia (AML), including the BCL-2 inhibitor venetoclax. Maximizing efficacy of these treatments requires refining patient selection. To this end, we analyzed two recent AML studies profiling the gene expression and ex vivo drug response of primary patient samples. We find that ex vivo samples often exhibit a general sensitivity to (any) drug exposure, independent of drug target. We observe that this “general response across drugs” (GRD) is associated with FLT3-ITD mutations, clinical response to standard induction chemotherapy, and overall survival. Further, incorporating GRD into expression-based regression models trained on one of the studies improved their performance in predicting ex vivo response in the second study, thus signifying its relevance to precision oncology efforts. We find that venetoclax response is independent of GRD but instead show that it is linked to expression of monocyte-associated genes by developing and applying a multi-source Bayesian regression approach. The method shares information across studies to robustly identify biomarkers of drug response and is broadly applicable in integrative analyses.

PMID:34302041 | DOI:10.1038/s41698-021-00209-9

Sci Rep. 2021 Jul 23;11(1):15128. doi: 10.1038/s41598-021-94635-1.

ABSTRACT

This cross-sectional study investigated the characteristics of cervical HPV infection in Changsha area and explored the influence of Candida vaginitis on this infection. From 11 August 2017 to 11 September 2018, 12,628 outpatient participants ranged from 19 to 84 years old were enrolled and analyzed. HPV DNA was amplified and tested by HPV GenoArray Test Kit. The vaginal ecology was detected by microscopic and biochemistry examinations. The diagnosis of Candida vaginitis was based on microscopic examination (spores, and/or hypha) and biochemical testing (galactosidase) for vaginal discharge by experts. Statistical analyses were performed using SAS 9.4. Continuous and categorical variables were analyzed by t-tests and by Chi-square tests, respectively. HPV infection risk factors were analyzed using multivariate logistic regression. Of the total number of participants, 1753 were infected with HPV (13.88%). Females aged ≥ 40 to < 50 years constituted the largest population of HPV-infected females (31.26%). The top 5 HPV subtypes affecting this population of 1753 infected females were the following: HPV-52 (28.01%), HPV-58 (14.83%), CP8304 (11.47%), HPV-53 (10.84%), and HPV-39 (9.64%). Age (OR 1.01; 95% CI 1-1.01; P < 0.05) and alcohol consumption (OR 1.30; 95% CI 1.09-1.56; P < 0.01) were found to be risk factors for HPV infection. However, the presence of Candida in the vaginal flora was found to be a protective factor against HPV infection (OR 0.62; 95% CI 0.48-0.8; P < 0.001). Comparing with our previous study of 2016, we conclude that the subtype distribution of HPV infection is relatively constant in Changsha. Our data suggest a negative correlation between vaginal Candida and HPV, however, more radical HPV management is required in this area for perimenopausal women and those who regularly consume alcohol.

PMID:34302031 | DOI:10.1038/s41598-021-94635-1

Sci Rep. 2021 Jul 23;11(1):15114. doi: 10.1038/s41598-021-94473-1.

ABSTRACT

Preliminary data have produced conflicting results regarding whether initial vitamin C levels in patients with severe sepsis correlate with mortality outcomes. We hypothesized that low plasma ascorbic acid or thiamine levels in severe sepsis patients admitted from the Emergency Department (ED) to the Intensive Care Unit (ICU) would be associated with increased mortality and an increased incidence of shock. Retrospective analysis of a prospective database of severe sepsis patients admitted to the ICU at an urban, academic medical center. Ascorbic acid and thiamine levels were analyzed in relation to survivors vs. non-survivors and shock vs. non-shock patients. 235 patients were included; mean age, 59.4 years ± 16.8 years; male, 128 (54.5%); in-hospital mortality, 16.6% (39/235); mean APACHE3 score, 61.8 ± 22.8; mean ascorbic acid level (reference range 0.40-2.10 mg/dL), 0.23 mg/dL (95% CI 0.07-4.02); and the mean thiamine level (reference range 14.6-29.5 nmol/L), 6.0 nmol/L (95% CI 4.0-9.5). When survivors were compared to non-survivors, survivors were more likely to be male (57.7% [113/196] vs. 38.5% [15/39]) and have lower APACHE3 scores (58.2 ± 22.6 vs. 79.9 ± 16.0). For the total cohort of 235 patients, there was no statistically significant relationship between a patient’s initial ascorbic acid or thiamine level and either survival or development of shock. In this analysis of early plasma samples from patients with severe sepsis admitted from the ED to the ICU, we found that mean ascorbic acid and thiamine levels were lower than normal range but that there was no relationship between these levels and outcomes, including 28 day mortality and development of shock.

PMID:34302025 | DOI:10.1038/s41598-021-94473-1

Sci Rep. 2021 Jul 23;11(1):15099. doi: 10.1038/s41598-021-94293-3.

ABSTRACT

We investigated the unfolding property and rotational stability of a new toric intraocular lens (IOL); TECNIS toric II (toric-II, ZCW, Johnson & Johnson) that is an improved version of TECNIS toric IOL (toric-I, ZCV). Both IOLs are based on an identical platform, except for the frosted haptics with toric-II IOL. The study consisted of two parts; experimental study and clinical, retrospective, case series. Experimental study indicated that the overall time from IOL ejection to unfolding to 11 mm was significantly shorter with toricII than toric-I IOLs (p = 0.032), due to the earlier separation of the haptics from the optic with toric-II IOL. Clinical study included 131 eyes of 99 patients who had undergone phacoemulsification and toric IOL implantation. At 3 months postoperatively, toric-II IOL showed significantly better rotational stability than toric-I IOL, including smaller residual manifest astigmatism (p = 0.018), less amount of axis misalignment from the intended axis (p = 0.04), lower incidence of misalignment > 10º (p = 0.0044), and less degree of prediction errors (p = 0.043). Postoperative uncorrected distance visual acuity tended to be better in the toric-II than in the toric-I groups, with marginal statistical difference (p = 0.057). TECNIS toric II IOL with the frosted haptics showed significantly better rotational stability than its predecessor, probably due to quicker unfolding and greater friction with the capsular bag.

PMID:34302005 | DOI:10.1038/s41598-021-94293-3

Sci Rep. 2021 Jul 23;11(1):15096. doi: 10.1038/s41598-021-94013-x.

ABSTRACT

Within the theory of statistical ensemble, the so-called [Formula: see text] ensemble describes equilibrium systems that exchange energy, particles, and volume with the surrounding. General, model-independent features of volume and particle number statistics are derived. Non-analytic points of the partition function are discussed in connection with divergent fluctuations and ensemble equivalence. Quantum and classical ideal gases, and a model of Bose gas with mean-field interactions are discussed as examples of the above considerations.

PMID:34301996 | DOI:10.1038/s41598-021-94013-x

Neurourol Urodyn. 2021 Jul 23. doi: 10.1002/nau.24752. Online ahead of print.

ABSTRACT

AIMS: Although abdominal sacrocolpopexy (ASC) is considered the gold standard for surgical repair of vaginal vault prolapse, the open surgical approach has significant morbidity. We aim to compare anatomic and functional outcomes in women receiving either robotic-assisted sacral colpopexy (RSC) or ASC for post-hysterectomy prolapse.

METHODS: We present a retrospective chart review of all women who underwent ASC and RSC at our institution and had 12-month follow-up (FU). Pelvic organ prolapse quantification (POP-Q) staging was assessed both preoperatively and postoperatively. Perioperative and demographic details were collected from the medical records.

RESULTS: One hundred twenty four women underwent RSC (mean age 63, median FU 16 months). Those in the ASC group (n = 144) were statistically younger (mean age 60) and had longer FU (median 60 months). Both median day of successful voiding trial and discharge day significantly favored RSC. There were no Clavien Grade IV/V complications for either procedure and three RSC procedures were converted to ASC. Both approaches were associated with a significant improvement in POP-Q stage at FU, with few women requiring additional surgery. Overall, 76% of women in each group were dry from stress urinary incontinence. Improvement in storage and emptying indices, dyspareunia, and quality of life measures was observed after both approaches.

CONCLUSION: RSC demonstrates good support of significant vaginal vault prolapse at medium term FU, with shorter hospital stays and low complication rates. Close FU after RSC over a longer period will be needed to fully assess durability of both functional and anatomic outcomes.

PMID:34298584 | DOI:10.1002/nau.24752

Vet Comp Orthop Traumatol. 2021 Jul 23. doi: 10.1055/s-0041-1731808. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to validate an imaging technique for evaluation of spinal surgery accuracy and to establish accuracy and safety of freehand technique in the thoracolumbar spine of large breed dogs.

STUDY DESIGN: After thoracolumbar spine computed tomography (CT), 26 drilling corridors were planned then drilled to receive 3.2 mm positive profile pins using a freehand technique. After pin removal, CT was repeated. All entry points, exit points and angles of the preoperative planned trajectories were compared with postoperative ones using an image registration and fusion technique by three observers. Corridor coordinates for entry and exit points were evaluated in three dimensions and angles were measured in one plane. Intraclass correlation coefficient (ICC) was used to establish the imaging technique reliability and descriptive statistics were used to report on the freehand technique accuracy. Safety was evaluated using a vertebral cortical breach grading scheme.

RESULTS: Intraclass correlation coefficient for the entry points, exit points and angle were 0.79, 0.96 and 0.92 respectively. Mean deviations for the entry points, exit points and angle were 3.1 mm, 6.3 mm and 7.6 degrees respectively. Maximum deviations were 6.3 mm, 11.0 mm and 16.4 degrees. Most deviations were lateral and caudal. All corridors were judged as safe.

CONCLUSION: The imaging technique reliability was good to excellent to study spinal surgery accuracy. Implant deviations should be anticipated when planning stabilization surgery in large breed dogs using the freehand-guided technique.

PMID:34298579 | DOI:10.1055/s-0041-1731808

J Neurosurg Pediatr. 2021 Jul 23:1-12. doi: 10.3171/2021.2.PEDS20810. Online ahead of print.

ABSTRACT

OBJECTIVE: The safety of stereo-electroencephalography (SEEG) has been investigated; however, most studies have not differentiated pediatric and adult populations, which have different anatomy and physiology. The purpose of this study was to assess SEEG safety in the pediatric setting, focusing on surgical complications and the identification of patient and surgical risk factors, if any. The authors also aimed to determine whether robot assistance in SEEG was associated with a change in practice, surgical parameters, and clinical outcomes.

METHODS: The authors retrospectively studied all SEEG cases performed in their department from December 2014 to March 2020. They analyzed both demographic and surgical variables and noted the types of surgery-related complications and their management. They also studied the clinical outcomes of a subset of the patients in relation to robot-assisted and non-robot-assisted SEEG.

RESULTS: Sixty-three children had undergone 64 SEEG procedures. Girls were on average 3 years younger than the boys (mean age 11.1 vs 14.1 years, p < 0.01). The overall complication rate was 6.3%, and the complication rate for patients with left-sided electrodes was higher than that for patients with right-sided electrodes (11.1% vs 3.3%), although the difference between the two groups was not statistically significant. The duration of recording was positively correlated to the number of implanted electrodes (r = 0.296, p < 0.05). Robot assistance was associated with a higher number of implanted electrodes (mean 12.6 vs 7.6 electrodes, p < 0.0001). Robot-assisted implantations were more accurate, with a mean error of 1.51 mm at the target compared to 2.98 mm in nonrobot implantations (p < 0.001). Clinical outcomes were assessed in the first 32 patients treated (16 in the nonrobot group and 16 in the robot group), 23 of whom proceeded to further resective surgery. The children who had undergone robot-assisted SEEG had better eventual seizure control following subsequent epilepsy surgery. Of the children who had undergone resective epilepsy surgery, 42% (5/12) in the nonrobot group and 82% (9/11) in the robot group obtained an Engel class IA outcome at 1 year (χ2 = 3.885, p = 0.049). Based on Kaplan-Meier survival analysis, the robot group had a higher seizure-free rate than the nonrobot group at 30 months postoperation (7/11 vs 2/12, p = 0.063). Two complications, whose causes were attributed to the implantation and head-bandaging steps, required surgical intervention. All complications were either transient or reversible.

CONCLUSIONS: This is the largest single-center, exclusively pediatric SEEG series that includes robot assistance so far. SEEG complications are uncommon and usually transient or treatable. Robot assistance enabled implantation of more electrodes and improved epilepsy surgery outcomes, as compared to those in the non-robot-assisted cases.

PMID:34298516 | DOI:10.3171/2021.2.PEDS20810

J Neurosurg Spine. 2021 Jul 23:1-8. doi: 10.3171/2020.12.SPINE201741. Online ahead of print.

ABSTRACT

OBJECTIVE: Survival scoring systems for spine metastasis (SPM) were designed to help surgical practice. The authors sought to validate the prognostic accuracy of the main preoperative scoring systems for SPM.

METHODS: It was hypothesized that true patient survival in SPM was better than that predicted using prognosis scores. To investigate this hypothesis, the authors designed a French national retrospective study of a prospectively collected multicenter database involving 739 patients treated for SPM between 2014 and 2017.

RESULTS: In this series, the median survival time for all patients from an SPM diagnosis was 17.03 ± 1.5 months. Sensitivity and specificity were estimated using the area under the curve (AUC). The AUC of Tomita’s prognosis score was the lowest and poorest (0.4 ± 0.023, range 0.35-0.44), whereas the AUC of the Tokuhashi score was the highest (0.825). The Lei score presented an AUC of 0.686 ± 0.022 (range 0.64-0.7), and the Rades score showed a weaker AUC (0.583 ± 0.020, range 0.54-0.63). Differences among AUCs were all statistically significant (p < 0.001). The modified Bauer score and the Rades score had the highest rate of agreement in predicting survival, with a weighted Cohen’s kappa of 0.54 and 0.41, respectively, indicating a moderate agreement. The revised Tokuhashi and Lei scores had a fair rate of agreement (weighted Cohen’s kappa = 0.24 and 0.22, respectively). The van der Linden and Tomita scores demonstrated the worst performance, with only a “slight” rate of agreement (weighted Cohen’s kappa = 0.19 and 0.16, respectively) between what was predicted and the actual survival.

CONCLUSIONS: The use of prognostic scoring systems in the estimation of survival in patients with SPM has become obsolete and therefore underestimates survival. Surgical treatment decisions should no longer be based on survival estimations alone but must also take into account patient symptoms, spinal instability, and quality of life.

PMID:34298515 | DOI:10.3171/2020.12.SPINE201741

J Neurosurg Pediatr. 2021 Jul 23:1-11. doi: 10.3171/2021.2.PEDS2121. Online ahead of print.

ABSTRACT

OBJECTIVE: Endoscopic third ventriculostomy (ETV), with or without choroid plexus cauterization (±CPC), is a technique used for the treatment of pediatric hydrocephalus. Rigid or flexible neuroendoscopy can be used, but few studies directly compare the two techniques. Here, the authors sought to compare these methods in treating pediatric hydrocephalus.

METHODS: A systematic MEDLINE search was conducted using combinations of keywords: “flexible,” “rigid,” “endoscope/endoscopic,” “ETV,” and “hydrocephalus.” Inclusion criteria were as follows: English-language studies with patients 2 years of age and younger who had undergone ETV±CPC using rigid or flexible endoscopy for hydrocephalus. The primary outcome was ETV success (i.e., without the need for further CSF diversion procedures). Secondary outcomes included ETV-related and other complications. Statistical significance was determined via independent t-tests and Mood’s median tests.

RESULTS: Forty-eight articles met the study inclusion criteria: 37 involving rigid endoscopy, 10 involving flexible endoscopy, and 1 propensity scored-matched comparison. A cumulative 560 patients had undergone 578 rigid ETV±CPC, and 661 patients had undergone 672 flexible ETV±CPC. The flexible endoscopy cohort had a significantly lower average age at the time of the procedure (0.33 vs 0.53 years, p = 0.001) and a lower preoperatively predicted ETV success score (median 40, IQR 32.5-57.5 vs 62.5, IQR 50-70; p = 0.033). Average ETV success rates in the rigid versus flexible groups were 54.98% and 59.65% (p = 0.63), respectively. ETV-related complication rates did not differ significantly at 0.63% for flexible endoscopy and 3.46% for rigid endoscopy (p = 0.30). There was no significant difference in ETV success or complication rate in comparing ETV, ETV+CPC, and ETV with other concurrent procedures.

CONCLUSIONS: Despite the lower expected ETV success scores for patients treated with flexible endoscopy, the authors found similar ETV success and complication rates for ETV±CPC with flexible versus rigid endoscopy, as reported in the literature. Further direct comparison between the techniques is necessary.

PMID:34298514 | DOI:10.3171/2021.2.PEDS2121