Nevin Manimala

Zhonghua Zhong Liu Za Zhi. 2022 Jul 23;44(7):767-775. doi: 10.3760/cma.j.cn112152-20200102-00002.

ABSTRACT

Objective: To investigate the value of predicting the degree of differentiation of pulmonary invasive adenocarcinoma (IAC) based on CT image radiomics model and the expression difference of immunohistochemical factors between different degrees of differentiation of lesions. Methods: The clinicopathological data of patients with pulmonary IAC confirmed by surgical pathology in the Affiliated Huai’an First People’s Hospital to Nanjing Medical University from December 2017 to September 2018 were collected. High-throughput feature acquisition was performed for all outlined regions of interest, and prediction models were constructed after dimensionality reduction by the minimum absolute shrinkage operator. Receiver operating characteristic curve was used to assess the predictive efficacy of clinical characteristic model, radiomics model and individualized prediction model combined with both to identify the degree of pulmonary IAC differentiation, and immunohistochemical expressions of Ki-67, NapsinA and TTF-1 were compared between groups with different degrees of IAC differentiation using rank sum test. Results: A total of 396 high-throughput features were extracted from all IAC lesions, and 10 features with high generalization ability and correlation with the degree of IAC differentiation were screened. The mean radiomics score of poorly differentiated IAC in the training group (1.206) was higher than that of patients with high and medium differentiation (0.969, P=0.001), and the mean radiomics score of poorly differentiated IAC in the test group (1.545) was higher than that of patients with high and medium differentiation (-0.815, P<0.001). The differences in gender (P<0.001), pleural stretch sign (P=0.005), and burr sign (P=0.033) were statistically significant between patients in the well and poorly differentiated IAC groups. Multifactorial logistic regression analysis showed that gender and pleural stretch sign were related to the degree of IAC differentiation (P<0.05). The clinical feature model consisted of age, gender, pleural stretch sign, burr sign, tumor vessel sign, and vacuolar sign, and the individualized prediction model consisted of gender, pleural stretch sign, and radiomic score, and was represented by a nomogram. The Akaike information standard values of the radiomics model, clinical feature model and individualized prediction model were 54.756, 82.214 and 53.282, respectively. The individualized prediction model was most effective in identifying the degree of differentiation of pulmonary IAC, and the area under the curves (AUC) of the individualized prediction model in the training group and the test group were 0.92 (95% CI: 0.86-0.99) and 0.88 (95% CI: 0.74-1.00, respectively). The AUCs of the radiomics group model for predicting the degree of differentiation of pulmonary IAC in the training group and the test group were 0.91 (95% CI: 0.83-0.98) and 0.87 (95% CI: 0.72-1.00), respectively. The AUCs of the clinical characteristics model for predicting the degree of differentiation of pulmonary IACs in the training and test groups were 0.75 (95% CI: 0.63-0.86) and 0.76 (95% CI: 0.59-0.94), respectively. The expression level of Ki-67 in poorly differentiated IAC was higher than that in well-differentiated IAC (P<0.001). The expression levels of NapsinA, TTF-1 in poorly differentiated IAC were higher than those in well-differentiated IAC (P<0.05). Conclusions: Individualized prediction model consisted of gender, pleural stretch sign and radiomics score can discriminate the differentiation degree of IAC with the best performance in comparison with clinical feature model and radiomics model. Ki-67, NapsinA and TTF-1 express differently in different degrees of differentiation of IAC.

PMID:35880343 | DOI:10.3760/cma.j.cn112152-20200102-00002

Zhonghua Zhong Liu Za Zhi. 2022 Jul 23;44(7):743-760. doi: 10.3760/cma.j.cn112152-20210824-00638.

ABSTRACT

Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn’t be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn’t be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.

PMID:35880341 | DOI:10.3760/cma.j.cn112152-20210824-00638

Cardiovasc Diabetol. 2022 Jul 25;21(1):139. doi: 10.1186/s12933-022-01574-w.

ABSTRACT

BACKGROUND: Recent studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) can achieve significant improvement in blood pressure in people with diabetes. Furthermore, randomized controlled trials (RCTs) have established that SGLT2i have a cardioprotective effect in adults with heart failure (HF). Therefore, we performed this systematic review an meta-analysis to determine the effect of SGLT2i on blood pressure in patients with HF.

METHODS: We used the Medline, Cochrane Library, Embase, and PubMed databases to identify RCTs (published through to April 29, 2022) that evaluated the effect of SGLT2i on HF. The primary endpoint was defined as change in blood pressure. Secondary composite outcomes were heart rate, hematocrit, body weight, and glycated hemoglobin. The N-terminal pro-brain natriuretic peptide level, Kansas City Cardiomyopathy Questionnaire scores, and estimated glomerular filtration rate were also evaluated.

RESULTS: After a literature search and detailed evaluation, 16 RCTs were included in the quantitative analysis. Pooled analyses showed that SGLT2i were associated with a statistically significant reduction in systolic blood pressure of 1.68 mmHg (95% confidence interval [CI] – 2.7, – 0.66; P = 0.001; I² = 45%) but not diastolic blood pressure (mean difference [MD] -1.06 mmHg; 95% CI -3.20, 1.08; P = 0.33; I² = 43%) in comparison with controls. Furthermore, SGLT2i decreased body weight (MD – 1.36 kg, 95% CI – 1.68, – 1.03; P < 0.001; I² = 61%) and the glycated hemoglobin level (MD – 0.16%, 95% CI – 0.28, -0.04, P = 0.007; I² = 91%) but increased hematocrit (MD 1.63%, 95% CI 0.63, 2.62, P = 0.001; I² = 100%). There was no significant between-group difference in heart rate (MD – 0.35; 95% CI – 2.05, 1.35, P = 0.69; I² = 0).

CONCLUSIONS: SGLT2i decreased systolic blood pressure in patients with HF but had no effect on diastolic blood pressure. These inhibitors may have numerous potentially beneficial clinical effects in patients with HF.

PMID:35879763 | DOI:10.1186/s12933-022-01574-w

BMC Musculoskelet Disord. 2022 Jul 25;23(1):705. doi: 10.1186/s12891-022-05675-1.

ABSTRACT

OBJECTIVE: This study assessed whether an enhanced recovery after surgery (ERAS) protocol could be beneficial for children with distal humerus fractures.

METHODS: Children with distal humerus fractures (n = 85) were randomly assigned to the ERAS and control groups and subjected to different perioperative managements. This was followed by the evaluation of their intraoperative characteristics (operation time and bleeding), postoperative characteristics (food intake conditions, pain scores, and discharge time), and postoperative functions.

RESULTS: The operation time, intraoperative bleeding, and postoperative hematological indices did not differ significantly between the two groups. Preoperative thirst and hunger were considerably less and the initial food intake duration following surgery was markedly shorter in the ERAS group than in the control group, whereas no difference between the groups was observed in the incidences of postoperative nausea and vomiting. A markedly reduced highest postoperative pain score and reduced mean pain score and demand for additional analgesic interventions were observed in the ERAS group compared with those in the control group, although the differences were not statistically significant. No noticeable between-group differences were observed in the incidences of postoperative incision problems, aspirational pneumonia, and gastroesophageal reflux. The total length of hospital stay was not significantly different between the two groups. However, the length of postoperative hospital stay was remarkably shorter and the elbow joint function at 2 months after surgery was significantly improved in the ERAS group compared with those in the control group.

CONCLUSION: The ERAS protocol can ameliorate preoperative discomfort and postoperative pain, shorten the postoperative hospital stay, and accelerate postoperative functional recovery without increasing the risks of postoperative nausea, vomiting, and poor incision healing and is, therefore, worthy of clinical application.

PMID:35879748 | DOI:10.1186/s12891-022-05675-1

Alzheimers Res Ther. 2022 Jul 25;14(1):102. doi: 10.1186/s13195-022-01049-w.

ABSTRACT

BACKGROUND: Cognitive reserve and resilience are terms used to explain interindividual variability in maintenance of cognitive health in response to adverse factors, such as brain pathology in the context of aging or neurodegenerative disorders. There is substantial interest in identifying tractable substrates of resilience to potentially leverage this phenomenon into intervention strategies. One way of operationalizing cognitive resilience that has gained popularity is the residual method: regressing cognition on an adverse factor and using the residual as a measure of resilience. This method is attractive because it provides a statistical approach that is an intuitive match to the reserve/resilience conceptual framework. However, due to statistical properties of the regression equation, the residual approach has qualities that complicate its interpretation as an index of resilience and make it statistically inappropriate in certain circumstances.

METHODS AND RESULTS: We describe statistical properties of the regression equation to illustrate why the residual is highly correlated with the cognitive score from which it was derived. Using both simulations and real data, we model common applications of the approach by creating a residual score (global cognition residualized for hippocampal volume) in individuals along the AD spectrum. We demonstrate that in most real-life scenarios, the residual measure of cognitive resilience is highly correlated with cognition, and the degree of this correlation depends on the initial relationship between the adverse factor and cognition. Subsequently, any association between this resilience metric and an external variable may actually be driven by cognition, rather than by an operationalized measure of resilience. We then assess several strategies proposed as potential solutions to this problem, such as including both the residual and original cognitive measure in a model. However, we conclude these solutions may be insufficient, and we instead recommend against “pre-regression” strategies altogether in favor of using statistical moderation (e.g., interactions) to quantify resilience.

CONCLUSIONS: Caution should be taken in the use and interpretation of the residual-based method of cognitive resilience. Rather than identifying resilient individuals, we encourage building more complete models of cognition to better identify the specific adverse and protective factors that influence cognitive decline.

PMID:35879736 | DOI:10.1186/s13195-022-01049-w

Perioper Med (Lond). 2022 Jul 26;11(1):28. doi: 10.1186/s13741-022-00260-5.

ABSTRACT

BACKGROUND: Prehabilitation appears to be an effective strategy to reduce postoperative complications and enhance recovery after colorectal surgery. Although many patients prefer (unsupervised) home-based prehabilitation, adherence can be problematic. Combining home-based prehabilitation with tele-monitoring might demonstrate a higher adherence than unsupervised prehabilitation; however, evidence on its feasibility and effectiveness in patients with colorectal cancer scheduled for elective surgery who are at high risk for postoperative complications is lacking. The aim of this study was to assess the feasibility of a bimodal tele-prehabilitation program in patients with colorectal cancer at high risk for postoperative complications.

METHODS: High-risk patients (oxygen uptake at the ventilatory anaerobic threshold ≤11 mL/kg/min or oxygen uptake at peak exercise ≤ 18 mL/kg/min) with colorectal cancer were included in a home-based bimodal tele-prehabilitation program. The program consisted of a personalized tele-monitored moderate to high-intensity interval training intervention and nutritional counseling. Feasibility was measured by participation rate, dropout rate, adherence to the physical exercise training session’s frequency, intensity, and time, and retention rate. Patient appreciation was measured by a patient appreciation questionnaire. Changes in preoperative physical fitness as secondary outcomes were quantified by time to exhaustion on a constant work rate (cycle) test, number of repetitions on the 30-s chair-stand test, and walking speed on the 4-m gait speed test.

RESULTS: The participation rate was 81%, there were no adverse events, and all participants managed to complete the tele-prehabilitation program (retention rate of 100%). Adherence with regard to the exercise program’s frequency, intensity, and time was respectively 91%, 84%, and 100%. All participants appreciated the tele-prehabilitation program. Time to exhaustion on the constant work rate test improved (not statistically significant) from a pre-prehabilitation median score of 317 seconds to a post-prehabilitation median score of 412 seconds (p = 0.24). Median number of repetitions on the 30-s chair-stand test improved from 12 to 16 (p = 0.01).

CONCLUSIONS: Tele-prehabilitation seems feasible in high-risk patients with colorectal cancer, but efforts should be made to further improve adherence to physical exercise training intensity. More research is needed to establish the (cost-)effectiveness of tele-prehabilitation regarding preoperative improvements in preoperative aerobic fitness and postoperative reduction of complications.

TRIAL REGISTRATION: ISRCTN, ISRCTN64482109 . Registered 09 November 2021 – Retrospectively registered.

PMID:35879732 | DOI:10.1186/s13741-022-00260-5

Genome Biol. 2022 Jul 25;23(1):162. doi: 10.1186/s13059-022-02729-4.

ABSTRACT

Two-dimensional high-throughput data have become increasingly common in functional genomics studies, which raises new challenges in data analysis. Here, we introduce a new statistic called Zeta, initially developed to identify global splicing regulators from a two-dimensional RNAi screen, a high-throughput screen coupled with high-throughput functional readouts, and ZetaSuite, a software package to facilitate general application of the Zeta statistics. We compare our approach with existing methods using multiple benchmarked datasets and then demonstrate the broad utility of ZetaSuite in processing public data from large-scale cancer dependency screens and single-cell transcriptomics studies to elucidate novel biological insights.

PMID:35879727 | DOI:10.1186/s13059-022-02729-4

Radiat Oncol. 2022 Jul 25;17(1):131. doi: 10.1186/s13014-022-02103-5.

ABSTRACT

BACKGROUND: Dose-escalation to above 80 Gy during external beam radiotherapy for localised prostate cancer leads to improved oncological outcomes but also substantially increased rectal toxicity. The aim of this study was to demonstrate the safety and efficacy of escalating the dose to 82 Gy following insertion of a peri-rectal hydrogel spacer (HS) prior to radiotherapy.

METHODS: This was a single arm, open-label, prospective study of men with localised prostate cancer who were prescribed a course of intensity modulated radiotherapy escalated to 82 Gy in 2 Gy fractions following insertion of the SpaceOAR™ HS (Boston Scientific, Marlborough, MA). Patients were prescribed a standard course of 78 Gy in 2 Gy fractions where rectal dose constraints could not be met for the 82 Gy plan. The co-primary endpoints were the rate of grade 3 gastrointestinal (GI) and genitourinary (GU) adverse events (CTCAE, v4), and patient-reported quality of life (QoL) (EORTC QLQ-C30 and PR25 modules), up to 37.5 months post-treatment.

RESULTS: Seventy patients received treatment on the study, with 64 (91.4%) receiving an 82 Gy treatment course. The median follow-up time post-treatment was 37.4 months. The rate of radiotherapy-related grade 3 GI and GU adverse events was 0% and 2.9%, respectively. There were 2 (2.9%) grade 3 adverse events related to insertion of the HS. Only small and transient declines in QoL were observed; there was no clinically or statistically significant decline in QoL beyond 13.5 months and up to 37.5 months post-treatment, compared to baseline. No late RTOG-defined grade ≥ 2 GI toxicity was observed, with no GI toxicity observed in any patient at 37.5 months post-treatment. Nine (12.9%) patients met criteria for biochemical failure within the follow-up period.

CONCLUSIONS: Dose-escalation to 82 Gy, facilitated by use of a hydrogel spacer, is safe and feasible, with minimal toxicity up to 37.5 months post-treatment when compared to rates of rectal toxicity in previous dose-escalation trials up to 80 Gy. Trials with longer follow-up of oncological and functional outcomes are required to robustly demonstrate a sustained widening of the therapeutic window. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12621000056897 , 22/01/2021. Retrospectively registered.

PMID:35879722 | DOI:10.1186/s13014-022-02103-5

BMC Nurs. 2022 Jul 25;21(1):199. doi: 10.1186/s12912-022-00984-1.

ABSTRACT

BACKGROUND: Standard precautions are minimum healthcare-associated infection prevention practices applied in all healthcare settings. The aim of this study was to investigate adherence to standard precautions using a survey and surveillance. Factors affecting observed adherence to standard precautions were also determined.

METHODS: This cross-sectional observational study included 163 clinical nurses who were directly involved in patient care. Differences in adherence according to investigative methods are represented as a boxplot. Quantile regression was used to identify factors affecting observed adherence, including organizational factors (such as department, safety environment, and patient safety climate) and personal factors (such as knowledge and awareness). Stata SE version 14.2 was used for all statistical analyses.

RESULTS: The observed adherence to standard precautions was 76.8 out of 100, whereas the self-reported adherence was approximately 95. Hand hygiene adherence received the lowest score of less than 70. Factors influencing observed adherence were self-reported adherence (p = 0.043) in 25% and 50% quantiles, work experience (p = 0.002) in the 25% quantile, and working department (p = 0.030) in the 50% quantile. There were no significant factors in the 75% quantile.

CONCLUSION: Inadequate adherence to standard precautions might increase healthcare-associated infections. Thus, an organizational environment such as nurse staffing needs to be established so that clinical nurses with high competency can comply with standard precautions in clinical settings.

PMID:35879717 | DOI:10.1186/s12912-022-00984-1

BMC Musculoskelet Disord. 2022 Jul 25;23(1):708. doi: 10.1186/s12891-022-05663-5.

ABSTRACT

TRIAL DESIGN: The prospective randomized controlled trial.

BACKGROUND: This study compares outcomes in terms of early postoperative anterior wrist pain and time to return to work or activities of daily living of patients who underwent carpal tunnel syndrome (CTS) release with short incision and those who had minimally invasive surgery (MIS) with CTS kits.

METHODS: A total of 24 patients diagnosed with primary CTS confirmed with electrodiagnosis at an academic university hospital were randomly assigned into one of two groups of 12 patients each: a short incision group and an MIS with tool-kit group using computer-generated block randomization (block of four). Sequentially numbered, opaque, sealed envelopes were used in the allocation concealment process. In the short incision group, skin was incised longitudinally from Kaplan’s line to the area distal to transverse wrist crease (2.5-4.0 cm) while in the tool-kit group, an incision of less than 2.5 cm. was made using special MIS-CTS kits. Primary outcomes evaluated include visual analogue scale (VAS) measurement of pain intensity in the anterior carpal area both while at rest and while conducting daily activities at the 2nd week postoperatively as well as the time to return to activities of daily living and work. Improvement in the Michigan hand questionnaire (MHQ) score, a secondary outcome, was also measured at the 2nd week postoperatively. Patients, allocator and outcome assessor were blinded.

RESULTS: Demographic data, including preoperative electrodiagnostic severity and occupation, were similar in the two groups. There were no significant differences in terms of VAS of the early postoperative anterior carpal area at rest (p > 0.99), while conducting daily activities (p = 0.89) and time to return to activities of daily living (p = 0.46) and work (p = 0.24). The MHQ score improvement at the 2nd week postoperatively showed no significant difference between the groups (p = 0.95). The MIS wound length in the tool-kit group was significantly shorter than in the short incision group (1.95 vs 2.92 cm, p < 0.01).

CONCLUSIONS: There is no difference in early postoperative anterior wrist pain, time to return to work or to activities of daily living between the surgical techniques. Short incision is recommended for benefit in term of cost-effectiveness, while MIS with tool-kit could be preferred in patients who concerned in cosmetic appearance between the surgical techniques.

TRIAL REGISTRATION: www.

CLINICALTRIALS: in.th (TCTR20200530003). Registered 30 May 2020.

PMID:35879713 | DOI:10.1186/s12891-022-05663-5