Nevin Manimala

Thorac Cancer. 2022 Sep 30. doi: 10.1111/1759-7714.14667. Online ahead of print.

ABSTRACT

BACKGROUND: Durvalumab consolidation is associated with improved survival following concurrent chemoradiotherapy (CCRT) in patients with stage III non-small cell lung cancer (NSCLC). Given the heterogeneity of stage III NSCLC patients, in this study we evaluated the efficacy and safety of durvalumab in the real-world setting.

METHOD: Unresectable stage III NSCLC patients were retrospectively studied: one cohort received CCRT, another had CCRT-durvalumab. Primary endpoints were progression-free survival (PFS) and overall survival (OS), secondary endpoints were relapse rate and safety. In CCRT-durvalumab cohort, association between blood markers with survival and pneumonitis risk were analyzed.

RESULTS: A total of 84 patients were enrolled: 45 received CCRT, and 39 received CCRT-durvalumab. Median PFS was 17.5 months for CCRT-durvalumab and 8.9 months for CCRT-alone (HR 0.47, p = 0.038). Median OS was not-reached for CCRT-durvalumab and 22.3 months for CCRT-alone (HR 0.35, p = 0.024). Both EGFR-positive and wild-type (WT) patients had numerically improved PFS with durvalumab consolidation compared to CCRT-alone, 17.5 versus 10.9 months and 11.8 versus 6.63 months, respectively (interaction p-value = 0.608). Grade 2+ pneumonitis was detected in 25% of patients in the durvalumab cohort. Most pneumonitis occurred at 3.5 weeks after durvalumab initiation. Baseline neutrophil-to-lymphocyte ratio (NLR) ≥ 3 and ≥5 were associated with shorter PFS with durvalumab. Week 6 platelet-lymphocyte-ratio ≥ 180 was associated with a lower risk of pneumonitis.

CONCLUSION: In this real-world study, durvalumab consolidation post CCRT was associated with a statistically significant improvement in PFS and OS. Effect of durvalumab on PFS was not modified by EGFR status. Active surveillance for pneumonitis is crucial. Baseline NLR may help to predict the benefit of treatment with durvalumab.

PMID:36177913 | DOI:10.1111/1759-7714.14667

Int J Oncol. 2022 Nov;61(5):141. doi: 10.3892/ijo.2022.5431. Epub 2022 Sep 30.

ABSTRACT

The present study aimed to investigate the potential molecular mechanisms by which galectin‑1 (Gal‑1) and glucose‑regulated protein 78 (GRP78) influence the development of malignant gastric cancer (GC). Immunohistochemistry and western blotting were used to map the expression and location of the Gal‑1 gene in the 80 paraffin‑embedded GC samples, 16 fresh samples and surrounding tissues. Gal‑1 was overexpressed and knocked down using lentiviral vectors in the human GC cell lines HGC‑27 and AGS. Through the use of the Cell Counting Kit‑8 assay, clone formation assay, wound healing assay, invasion assay and tumor xenograft, the possible biological roles of Gal‑1 were further evaluated. The downstream interacting proteins were predicted by the BioGRID database, and GRP78 was chosen for further investigation. Immunofluorescence labeling and Co‑IP were used to confirm the connection. The statistical tests utilized were the two‑tailed paired Student’s t‑test, χ² test, Kaplan‑Meier and Cox regression analysis, and Spearman’s rank correlation coefficients. In GC, Gal‑1 is extensively expressed and has the potential to interact with GRP78. Poor prognosis is linked to high levels of GRP78 and Gal‑1 expression in patients with GC. According to the functional study, Gal‑1 knockdown prevented cells from thriving and pushed Gal‑1 expression, which aided in the proliferation, migration and invasion of GC. Gal‑1 overexpression additionally aided the development of subcutaneous xenograft tumors. The mechanistic investigation proved that GRP78 and Gal‑1 interacted, accelerating the course of GC. Gal‑1 silencing had an inhibitory effect on the proliferation of HGC‑27 cells that was removed by ectopic GRP78 expression, whereas the stimulating effects of Gal‑1 overexpression in AGS cells were inhibited by GRP78 knockdown. In conclusion, Gal‑1 interacts with GRP78 to facilitate the advancement of GC. The Gal‑1/GRP78 axis is supported by the functional data of the present study as a possible GC treatment target.

PMID:36177897 | DOI:10.3892/ijo.2022.5431

Psychol Med. 2022 Sep 30:1-11. doi: 10.1017/S0033291722002999. Online ahead of print.

ABSTRACT

BACKGROUND: Posttraumatic Stress Disorder (PTSD) tends to co-occur with greater alcohol consumption as well as alcohol use disorder (AUD). However, it is unknown whether the same etiologic factors that underlie PTSD-alcohol-related problems comorbidity also contribute to PTSD- alcohol consumption.

METHODS: We used summary statistics from large-scale genome-wide association studies (GWAS) of European-ancestry (EA) and African-ancestry (AA) participants to estimate genetic correlations between PTSD and a range of alcohol consumption-related and alcohol-related problems phenotypes.

RESULTS: In EAs, there were positive genetic correlations between PTSD phenotypes and alcohol-related problems phenotypes (e.g. Alcohol Use Disorders Identification Test (AUDIT) problem score) (rGs: 0.132-0.533, all FDR adjusted p < 0.05). However, the genetic correlations between PTSD phenotypes and alcohol consumption -related phenotypes (e.g. drinks per week) were negatively associated or non-significant (rGs: -0.417 to -0.042, FDR adjusted p: <0.05-NS). For AAs, the direction of correlations was sometimes consistent and sometimes inconsistent with that in EAs, and the ranges were larger (rGs for alcohol-related problems: -0.275 to 0.266, FDR adjusted p: NS, alcohol consumption-related: 0.145-0.699, FDR adjusted p: NS).

CONCLUSIONS: These findings illustrate that the genetic associations between consumption and problem alcohol phenotypes and PTSD differ in both strength and direction. Thus, the genetic factors that may lead someone to develop PTSD and high levels of alcohol consumption are not the same as those that lead someone to develop PTSD and alcohol-related problems. Discussion around needing improved methods to better estimate heritabilities and genetic correlations in diverse and admixed ancestry samples is provided.

PMID:36177877 | DOI:10.1017/S0033291722002999

J Int Med Res. 2022 Sep;50(9):3000605221127520. doi: 10.1177/03000605221127520.

ABSTRACT

OBJECTIVE: Evidence indicates that people with a high body mass index (BMI) tend to develop more severe forms of coronavirus disease 2019 (COVID-19). In this study, we aimed to determine the association between the duration of COVID-19 symptoms and variables such as BMI, age, presence of comorbidities, and smoking in non-hospitalized patients.

METHODS: In this observational cross-sectional analytical study, we analyzed the data of patients with COVID-19 but without severe manifestations. We conducted descriptive statistics, non-parametric tests, and multivariate quasi-Poisson regression in the analysis. The quasi-Poisson regression model was configured with the duration of COVID-19 symptoms as the response variable, and BMI and the presence of comorbidities as the explanatory variables.

RESULTS: Among 302 non-hospitalized patients, we found a significant difference in COVID-19 symptom duration between the overweight group and the group with normal weight. Multivariate quasi-Poisson regression analysis showed that BMI and the presence of comorbidities were associated with the duration of COVID-19 symptoms. On the contrary, sex, age, and smoking status were not related to COVID-19 symptom duration.

CONCLUSIONS: BMI and comorbidities were associated with the duration of COVID-19 symptoms in non-hospitalized patients.

PMID:36177839 | DOI:10.1177/03000605221127520

J Int Med Res. 2022 Sep;50(9):3000605221126880. doi: 10.1177/03000605221126880.

ABSTRACT

OBJECTIVE: The clinical benefit of automatic temperature control devices remains unclear. We investigated the outcomes of out-of-hospital cardiac arrest (OHCA) survivors who had undergone either target temperature management (TTM) with a temperature feedback system (TFS) or maintenance of normothermia without a TFS during post-resuscitation care.

METHODS: This study was a retrospective analysis of a multicenter prospective cohort of OHCA survivors who had received postcardiac arrest care from August 2014 to December 2018. The overlap propensity score weighting method was applied for adjustment between groups.

RESULTS: A total of 405 OHCA survivors were included. TTM with a TFS and normothermia without a TFS were applied to 318 and 87 patients, respectively. Fever events were more common in patients with normothermia without a TFS. After propensity score matching, no statistically significant differences were observed in the 1-month good neurologic outcome (odds ratio 0.99, 95% confidence interval [CI] 0.56-1.25) or survival rate (odds ratio 1.25, 95% CI 0.88-1.78).

CONCLUSION: No significant differences in the 1-month neurologic outcome were observed between patients receiving TTM with a TFS and those undergoing normothermia without a TFS.

PMID:36177833 | DOI:10.1177/03000605221126880

Rev Esp Enferm Dig. 2022 Sep 30. doi: 10.17235/reed.2022.8838/2022. Online ahead of print.

ABSTRACT

Objective To explore the relationship between the expression of DEAH-box RNA helicase 15 (DHX15) in colorectal cancer (CRC), its clinical pathological features and survival prognosis. Method DHX15 expression data with clinic pathological features from the Cancer Gene Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), were statistically analyzed for the association between DHX15 expression and overall survival of CRC. The expression of DHX15 was performed by immunohistochemical staining (IHC) using tumor and the adjacent normal tissues mounted in tissue microarrays. The significance of DHX15 expression in predicting the survival and prognosis of CRC were analyzed using Kaplan-Meier method, Univariate and Multivariate Cox regression analysis. Results Low expression of DHX15 mRNA and DHX15 protein in CRC were both negative factors for survival prognosis. Overall survival of patients with low-expression of DHX15 was significantly lower (χ2=8.452, p=0.004) by Kaplan-Meier evaluation. Low expression of DHX15 in CRC tissues was correlated with distal lymph node metastasis (χ²=7.120, p=0.008), TNM stage (χ²=3.935, p=0.047) and disease recurrence (χ²=9.524, p=0.002) of CRC patients. Low expression of DHX15, (HR=4.012, 95%CI: 1.462~11.013, p=0.007), late TNM stage (HR=0.067, 95%CI: 0.029~0.156, p<0.001) and recurrence (HR=0.008, 95%CI: 0.002~0.034, p<0.001) were risk factors related to the prognosis of CRC patients by Univariate Cox regression analysis. Conclusion Our findings reveal a key role for DHX15 in the progress of CRC metastasis and recurrence. DHX15 may be a potential biomarker for CRC targeted therapy.

PMID:36177832 | DOI:10.17235/reed.2022.8838/2022

Orthop Surg. 2022 Sep 30. doi: 10.1111/os.13524. Online ahead of print.

ABSTRACT

OBJECTIVE: Early prediction of stem version aids in optimization of combined version during total hip arthroplasty (THA). This study aimed to analyze the discrepancy between stem version and native femoral version measured by different methods, and to explore which method can better predict the stem version.

METHODS: We retrospectively reviewed 26 patients (39 hips) treated with robot-assisted THA in our hospital between September 2019 and December 2019. A straight, single-wedge, cementless stem (Accolade II) was used in all cases. Preoperative femoral version was measured at three levels on computerized tomography (CT) scan from the top to the middle level of femoral neck (Level 1 to Level 3). During THA, the version on cutting surface was measured prior to femoral broaching based on two reference lines: mid-cortical line and T line (trochanteric fossa to the middle of medial cortex). After femoral broaching, stem version was measured based on the femoral neck trial using Mako system (Stryker). In the statistical analysis, the difference and absolute discrepancy between stem version and femoral version measured with various methods were examined using paired t-test, and the relationship between stem version and various femoral versions were examined using correlation analysis.

RESULTS: Mean femoral neck version (Level 1) was 9.5° ± 2.6° (range, -16.8°-42.5°), while mean stem version measured by Mako system was 19.9° ± 2.0° (range, -8.0°-49.0°). Femoral version measured with each method showed a moderate correlation with stem version (p < 0.05). There was a significant difference between stem version and femoral version except at Level 3, with a mean difference of 0.8° ± 13.6° (p = 0.729). With regard to the intraoperative estimation, stem version significantly increased compared to the value based on mid-cortical line, with a mean difference of 8.4° ± 13.1° (p < 0.001). However, the mean value of stem version was a little smaller than that of femoral version measured by reference to T line, but without statistical significance (p = 0.156). No postoperative dislocations occurred during the study period. No revision was required for any component.

CONCLUSIONS: The middle level of femoral neck on CT scan and T line on cutting surface are better references to measure femoral version for predicting postoperative stem version. However, the relationship between stem version and predictive value was flexible. Therefore, further three-dimensional studies of postoperative CT are needed to validate the press-fit fixation and rotational freedom of the single-wedge stem.

PMID:36177805 | DOI:10.1111/os.13524

Dermatol Ther. 2022 Sep 30:e15871. doi: 10.1111/dth.15871. Online ahead of print.

ABSTRACT

INTRODUCTION: Tofacitinib is a pan-janus kinase inhibitor (JAK) which has been tested off-label in alopecia areata (AA) with promising results. However, evidence of tofacitinib in real-life setting is still poor. We evaluated long-term efficacy and safety of tofacitinib for refractory AA.

MATERIAL AND METHODS: This is a prospective, open-label, observational, single-center cohort study conducted between January 2018 and December 2020. Primary end point was the percent change in Severity of Alopecia Tool (SALT) at the basal visit and at the most recent follow-up visit. Three categories of treatment response were analysed.

RESULTS: Data on 47 participants of Arab-Asian heritage were analysed. A complete and partial regrowth was observed in 18 patients (41.86%) and 11 patients (25.58%), respectively. In 12 patients (27.9%), no response was obtained. Most of the non-responders belonged to the alopecia universalis group (66.67%). No statistical differences were observed in rates of regrowth between pediatric and adult individuals (p=0.52), nor between women and men. Significant differences in the average duration of tofacitinib treatment were obtained among the three categories of regrowth (p<.003), notably duration of AA did not impact the clinical regrowth (p=0.62).

CONCLUSION: To the best of our knowledge, this is the first prospective, observational, long-term study using tofacitinib in refractory AA. Rates of regrowth and side effects are analogous to previous works. Length of tofacinitib therapy should last for 12 months before considering any discontinuation or chang, since early cessation can lead to treatment failures or incomplete regrowth. Maintenance therapy after complete regrowth has demonstrated to be safe and effective to prevent recurrences of hair loss. This article is protected by copyright. All rights reserved.

PMID:36177791 | DOI:10.1111/dth.15871

Clin Anat. 2022 Sep 30. doi: 10.1002/ca.23955. Online ahead of print.

ABSTRACT

INTRODUCTION: Safe intubation of newborns remains a challenge. This investigates the upper airway anatomy of (pre-)term infants was investigated to improve airway management and the development of airway devices.

MATERIALS AND METHODS: Angles and diameters of both oral and nasal intubation pathways of twenty-two cadavers of premature and term stillborn infants were measured, relative to their gestational age (GA) and tested for statistical significance. The systematic influence of sex on the distribution of values was examined. Cast models of the oral and nasal intubation pathway were (produced using a silicone dental impression material) 3D-scanned.

RESULTS: No significant correlation with GA was seen in the angles studied. However, four distances around the hard and soft palate did show statistically significant positive correlations with GA. Regarding differences between the sexes, only the angle between the entrance of the trachea and the esophagus was greater for male cadavers.

CONCLUSION: The angles of the ventilation pathway of (pre-)term infants do not depend systematically on GA. Anatomically, laryngeal masks might therefore also be well-suited ventilators for preterm infants. Alterations in the size but not the shape of laryngeal masks for small preterm infants is recommended. The data obtained may thus be used as a basis for the development of airway devices and airway simulators for medical education and clinical training. This article is protected by copyright. All rights reserved.

PMID:36177789 | DOI:10.1002/ca.23955

Ital J Dermatol Venerol. 2022 Sep 30. doi: 10.23736/S2784-8671.22.07386-8. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with atopic dermatitis (AD) display a defective skin barrier, consequently they may experience inflammatory flares with different exposures, including masks. Actually, beside scattering case reports, no study focused on the possible AD flaring due to masks.

METHODS: In this multicenter prospective study AD patients with facial manifestation were followed with teledermatology and evaluated by two board-certified dermatologists at the baseline (T0) and after 1 month (T1) in which patients started to wear masks >6 hours per day. Demographics and clinical parameters, included and not limited to Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI), were carefully collected and analyzed.

RESULTS: We enrolled 57 AD patients (M/F 28/29, 33.91 ± 12.26 yoa) that wore surgical masks (38 (66.7%)), community masks (11 (19.3%) and N95 (8 (14.0%)). Both DLQI and EASI increase during the time period (p<0.0001). DLQI variation was not influenced by age, BMI, and gender, mask type used and AD therapy (p=0.99), whilst EASI variation was significantly influenced by BMI, gender, and therapy (p=0.004).

CONCLUSIONS: Mask wearing may prove detrimental to patients with atopic eczema and the same may not necessarily be the case for asthma patients.

PMID:36177781 | DOI:10.23736/S2784-8671.22.07386-8