Significant Effect In Patients Research Articles

Appraisal of Olezarsen for Treatment of Hypertriglyceridemia

Olezarsen is antisense antinucleotide under investigation that inhibits synthesis of apolipoprotein C3 (ApoC3) resulting in reduction of plasma triglycerides levels. In a phase 3 clinical trial of patients having familial chylomicronemia syndrome (FCS) with extreme hypertriglyceridemia at baseline (mean plasma triglycerides 2,630 mg/dl), olezarsen 80 mg administered subcutaneously every 4 weeks decreased triglycerides by 43.5 percentage points (95% CI, 69.1 to 17.9; P<0.001) after 6 months compared with placebo. By 53 weeks, 1 episode of acute pancreatitis occurred in olezarsen group versus 11 episodes in the placebo group, rate ratio (RR) 0.12 (95% CI, 0.02 TO 0.66). Two phase 2 trials evaluated olezarsen in patients with moderately elevated triglycerides (<500 mg/dl) and high cardiovascular (CV) risk recorded similar magnitude of reduction of triglycerides. Olezarsen reduced levels of atherogenic lipoproteins such as ApoC3 by 73%, non-high-density lipoprotein cholesterol (non-HDL-C) by 17-23% and increased high-density lipoprotein cholesterol (HDL-C) levels by 30-40%. Meanwhile, olezarsen increased mean values of low-density lipoprotein (LDL-C) from 22.8 to 37.6 mg/dl in patients with FCS but had no significant effects in patients with high CV risk having higher baseline LDL-C levels. Discontinuation rates due to adverse effects of olezarsen were 9-12% versus 0% with placebo. The most common adverse effects of olezarsen were elevation of liver enzymes, mostly below 3 times the upper limit of normal, and injection-site reactions. Platelet count < 140,000/µl occurred in 18% in patients receiving olezarsen versus 3% with placebo (risk ratio 6.8; 95% CI, 0.91 to 51.3; P=0.03). No patient had severe thrombocytopenia with platelet number < 75,000/µl. Overall, olezarsen is a promising new therapy for hypertriglyceridemia and for prevention of hypertriglyceridemia-induced pancreatitis. Long-term randomized trials are urgently needed to examine the effects of olezarsen on CV events and mortality and establish its long-term safety.

Analysis of the Effect of Limb Rehabilitation Therapy Combined with Transcranial Magnetic Stimulation Therapy on Muscle Activity in Patients with Upper Limb Dysfunction After Cerebral Infarction

Objective: To analyze the effect of limb rehabilitation therapy combined with transcranial magnetic stimulation therapy on muscle activity in patients with upper limb dysfunction after cerebral infarction (CI). Methods: 320 patients with upper limb dysfunction after CI were selected, all of whom were treated in our hospital between June 2021 and June 2023. They were randomly grouped according to the lottery method into the control group (limb rehabilitation therapy, 160 cases) and the intervention group (transcranial magnetic stimulation therapy + limb rehabilitation therapy, 160 cases).The upper limb function scores, neuro-electrophysiological indicators, daily living ability scores, and quality of life scores of the two groups were compared. Results: Compared with the control group, upper limb function scores and daily living ability scores in the intervention group were higher after treatment, and the neuro-electrophysiological indicators of the intervention group were lower after treatment (P < 0.05). Conclusion: Transcranial magnetic stimulation therapy combined with limb rehabilitation therapy has significant effects in patients with upper limb dysfunction after CI and is worthy of promotion and application.

ZNF384 fusion transcript levels for measurable residual disease monitoring in adult B-cell acute lymphoblastic leukemia.

Zinc finger protein 384 (ZNF384) rearrangement defined a novel subtype of B-cell acute lymphoblastic leukemia (B-ALL). The prognostic significance of ZNF384 fusion transcript levels represented measurable residual disease remains to be explored. ZNF384 fusions were screened out in 57 adult B-ALL patients at diagnosis by real-time quantitative polymerase chain reaction and their transcript levels were serially monitored during treatment. The reduction of ZNF384 fusion transcript levels at the time of achieving complete remission had no significant impact on survival, whereas its ≥2.5-log reduction were significantly associated with higher relapse free survival (RFS) and overall survival (OS) rates after course 1 consolidation (p=0.022 and=0.0083) and course 2 consolidation (p=0.0025 and=0.0008). Compared with chemotherapy alone, allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improved RFS and OS of patients with <2.5-log reduction after course 1 consolidation (p<0.0001 and=0.0002) and course 2 consolidation (p=0.0003 and=0.019), whereas exerted no significant effects in patients with ≥2.5-log reduction (all p>0.05). ZNF384 fusion transcript levels after course 1 and course 2 consolidation strongly predict relapse and survival and may guide whether receiving allo-HSCT in adult B-ALL.

Non-invasive brain-computer interfaces effectively improve motor function, sensory function, and activities of daily living in patients with spinal cord injury: a systematic review and meta-analysis

After spinal cord injury (SCI), severe motor, sensory, and autonomic dysfunction of the limbs below the injury level occurs, significantly reducing the patient’s ability to perform activities of daily living (ADL) and quality of life. Brain-computer interface (BCI), as a new rehabilitation intervention, can extract brain signals, bypass the diseased segments, and translate them into commands to control external devices to restore the sensory and motor functions of SCI. However, the current high-quality research evidence for BCI treatment of SCI is insufficient, so this review aims to evaluate the effectiveness and feasibility of non-invasive BCI training for improving motor, sensory, and ADL in patients with SCI. The BCI-related trial literature was retrieved from seven databases (PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, WanFang database, and China Scientific Journals Full Text Database). A total of seven studies (n = 102 patients with SCI) were included for meta-analysis using a fixed-effect model, with effect sizes reported as standardized mean differences. BCI training effectively improve motor function in patients with SCI, especially those in the subacute phase, but to no significant effect in patients with chronic phase. Moreover, the treatment effect of BCI is better when the number of interventions is less than 30 times and a single session lasting longer than 60 minutes is more effective. BCI intervention also showed a positive impact for sensory function and ADL on patients with SCI, and improved quality of life in SCI patients. As a rehabilitation method, BCI has been proven to be effective in improving the motor function of patients with SCI. This provides more choices in future rehabilitation protocols for SCI.

Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging-Tractography in Resective Brain Surgery: Lesion Coverage Strategies and Patient Outcomes.

Diffusion tensor imaging (DTI)-tractography and functional magnetic resonance imaging (fMRI) have dynamically entered the presurgical evaluation context of brain surgery during the past decades, providing novel perspectives in surgical planning and lesion access approaches. However, their application in the presurgical setting requires significant time and effort and increased costs, thereby raising questions regarding efficiency and best use. In this work, we set out to evaluate DTI-tractography and combined fMRI/DTI-tractography during intra-operative neuronavigation in resective brain surgery using lesion-related preoperative neurological deficit (PND) outcomes as metrics. We retrospectively reviewed medical records of 252 consecutive patients admitted for brain surgery. Standard anatomical neuroimaging protocols were performed in 127 patients, 69 patients had additional DTI-tractography, and 56 had combined DTI-tractography/fMRI. fMRI procedures involved language, motor, somatic sensory, sensorimotor and visual mapping. DTI-tractography involved fiber tracking of the motor, sensory, language and visual pathways. At 1 month postoperatively, DTI-tractography patients were more likely to present either improvement or preservation of PNDs (p = 0.004 and p = 0.007, respectively). At 6 months, combined DTI-tractography/fMRI patients were more likely to experience complete PND resolution (p < 0.001). Low-grade lesion patients (N = 102) with combined DTI-tractography/fMRI were more likely to experience complete resolution of PNDs at 1 and 6 months (p = 0.001 and p < 0.001, respectively). High-grade lesion patients (N = 140) with combined DTI-tractography/fMRI were more likely to have PNDs resolved at 6 months (p = 0.005). Patients with motor symptoms (N = 80) were more likely to experience complete remission of PNDs at 6 months with DTI-tractography or combined DTI-tractography/fMRI (p = 0.008 and p = 0.004, respectively), without significant difference between the two imaging protocols (p = 1). Patients with sensory symptoms (N = 44) were more likely to experience complete PND remission at 6 months with combined DTI-tractography/fMRI (p = 0.004). The intraoperative neuroimaging modality did not have a significant effect in patients with preoperative seizures (N = 47). Lack of PND worsening was observed at 6 month follow-up in patients with combined DTI-tractography/fMRI. Our results strongly support the combined use of DTI-tractography and fMRI in patients undergoing resective brain surgery for improving their postoperative clinical profile.

A postbiotic fermented oat gruel may have a beneficial effect on the colonic mucosal barrier in patients with irritable bowel syndrome.

Impaired intestinal permeability and microbial dysbiosis are important pathophysiological mechanisms underlying irritable bowel syndrome (IBS). ReFerm®, also called Profermin®, is a postbiotic product of oat gruel fermented with Lactobacillus plantarum 299v. In this study, we investigated whether ReFerm® has a beneficial effect on the intestinal epithelial barrier function in patients with IBS. Thirty patients with moderate to severe IBS-diarrhoea (IBS-D) or IBS-mixed (IBS-M) were treated with enema containing ReFerm® or placebo. The patients underwent sigmoidoscopy with biopsies obtained from the distal colon at baseline and after 14 days of treatment with ReFerm® or placebo twice daily. The biopsies were mounted in Ussing chambers, and paracellular and transcellular permeabilities were measured for 120 min. In addition, the effects of ReFerm® or placebo on the epithelial barrier were investigated in vitro using Caco-2 cells. ReFerm® reduced paracellular permeability (p < 0.05) and increased transepithelial resistance (TER) over time (p < 0.01), whereas the placebo had no significant effect in patients. In ReFerm®-treated Caco-2 cells, paracellular and transcellular permeabilities were decreased compared to the control (p < 0.05) and placebo (p < 0.01). TER was increased in Caco-2 ReFerm®-treated cells, and normalised TER was increased in ReFerm®-treated Caco-2 cells compared to control (p < 0.05) and placebo-treated (p < 0.05) cells. ReFerm® significantly reduced paracellular permeability and improved TER in colonic biopsies collected from patients with IBS and in a Caco-2 cell model. Our results offer new insights into the potential benefits of ReFerm® in IBS management. Further studies are needed to identify the molecular mechanisms underlying the barrier-protective properties of ReFerm®. [https://clinicaltrials.gov/], identifier [NCT05475314].

Determination of the Efficacy of Daclatasvir Plus Sofosbuvir in Patients with Acute ‎Respiratory Coronavirus Syndrome (SARS-COV-2): A Randomized Clinical Trial

Background: To tackle the 2019 coronavirus infection (COVID-19) disease pandemic, effective antiviral therapy is critical. We assessed the efficacy of sofosbuvir and daclatasvir for treating patients with COVID-19.&#x0D; Methods: This was a randomized controlled trial in adults with moderate-to-severe COVID-19 disease admitted to Razi Teaching Hospital in Ahvaz, Khuzestan Province, Iran. Patients were randomly assigned to the sofosbuvir and daclatasvir group (n=35, intervention group) and control group (n=35, standard care). The primary endpoint of this study was the length of hospital stay, clinical improvement, mechanical ventilation, mortality, and side effect.&#x0D; Results: We found that the combination of Daclatasvir and Sofosbuvir (DCV+SOF) did not make a statistically significant difference in terms of mortality. There was no significant difference in the duration of hospitalization between the two groups. The two groups did not differ significantly in terms of the frequency of side effects. There were 2 cases of intubation and death in both groups.&#x0D; Conclusion: The medications used in this study, i.e, the combination of daclatasvir and sofosbuvir, failed to show a significant effect in patients, and despite promising laboratory studies, there were no improvements observed in vital signs and the indicators studied, including clinical signs. Hospitalization days, ventilator requirements and mortality did not make a significant difference. To confirm the results of this study, conducting researches with a larger sample size are needed.

Clinical Relevance of Myopenia and Myosteatosis in Colorectal Cancer.

Sarcopenia was initially described as a decrease in muscle mass associated with aging and subsequently also as a consequence of underlying disease, including advanced malignancy. Accumulating evidence shows that sarcopenia has clinically significant effects in patients with malignancy, including an increased risk of adverse events associated with medical treatment, postoperative complications, and a poor survival outcome. Colorectal cancer (CRC) is one of the most common cancers worldwide, and several lines of evidence suggest that preoperative sarcopenia negatively impacts various outcomes in patients with CRC. In this review, we summarize the current evidence in this field and the clinical relevance of sarcopenia in patients with CRC from three standpoints, namely, the adverse effects of medical treatment, postoperative infectious complications, and oncological outcomes.

Successful treatment of EGFR T790M-mutant non-small cell lung cancer with almonertinib after osimertinib-induced interstitial lung disease: a case report and literature review

Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have revolutionized the standard treatment for EGFR T790M-positive non-small cell lung cancer (NSCLC). Osimertinib is one of the third-generation EGFR-TKIs and is currently the most advanced in clinical development. Interstitial lung disease (ILD) is a potentially fatal side effect of osimertinib use. Successful rechallenge with the second-generation TKI afatinib following osimertinib-induced ILD has been reported. However, few reports have discussed the safety and efficacy of third-generation TKI rechallenge in this patient population. In this paper, a case of lung adenocarcinoma is retrospectively analyzed, and the relevant literature is reviewed. The patient was initially diagnosed with early lung cancer, for which surgical treatment was performed. The postoperative diagnosis indicated stage IB (pT2N0M0) right lung adenocarcinoma. Genetic testing (amplification-refractory mutation system) revealed EGFR exon 19 deletion. More than 2 years after surgery, multiple metastases occurred in both lungs, so gefitinib (250 mg per day) was administered. However, 6 months after the start of gefitinib treatment, the tumor progressed. Lung tumor biopsy was performed for genetic testing (NGS) and an EGFR T790M mutation was observed. Subsequently, second-line treatment with osimertinib (80 mg per day) was given for 3 months. The evaluated response suggested a partial response (PR) with the occurrence of grade 3 ILD. Pemetrexed plus bevacizumab chemotherapy was subsequently administered, resulting in stable disease. However, following a severe drug reaction after six courses, the patient’s chemotherapy was discontinued. Another third-generation TKI, almonertinib (110 mg per day), was rechallenged based on no ILD having been reported in a phase I/II study of this drug. After 4 months of almonertinib administration and 6 months without ILD recurrence, partial remission was attained. This is the first report of successful treatment with almonertinib after osimertinib-induced ILD. The results suggested that almonertinib had a significant effect in patients with EGFR T790M mutation, with fewer side effects and better survival benefits for patients with advanced lung cancer.

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression – a randomized controlled trial

BackgroundIntermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex (DMPFC) has shown promise in open-label trials of depression. MethodsIn this randomized, double-blind, sham controlled trial we evaluate iTBS over the DMPFC for anhedonia, avolition, and blunted affect in patients with schizophrenia or depression. Active iTBS was delivered over the DMPFC with 1200 pulses per session, twice daily over ten weekdays at target intensity with an angled figure-of eight coil. Sham condition comprised the magnetically shielded side of the coil and simultaneous transcutaneous electrical nerve stimulation. Primary outcome was change on the Clinical Assessment Interview for Negative Symptoms (CAINS). ResultsTwenty-eight patients were randomized to active iTBS and 28 to sham. Mean (standard deviation) change in CAINS score from baseline to the day after last treatment was -5.3 (8.1) in active iTBS and -2.1 (7.1) in sham. A linear model showed no significant effect of treatment, accounting for baseline scores p=.088. Sub analyses per diagnostic group showed a significant effect in patients with depression, p=.038, but not in the schizophrenia group, p=.850. However, overall depressive symptoms did not change significantly in patients with depression. There were three serious adverse events, all in the sham group. LimitationsPossibly too short treatment course and few patients with schizophrenia. ConclusionIn this first transdiagnostic randomized controlled trial of iTBS over DMPFC for anhedonia, avolition, and blunted affect it can be concluded that it was generally tolerable and safe but only more effective than sham in the subgroup of patients with depression.

Akraba Dışı Kordon Kanı Kaynaklı Kök Hücre Transplantasyonu Retrospektif Analizi

Objective: Cord blood stem cells are used for hematopoietic stem cell transplantation (HSCT) in the treatment of hematological malignant and non-malignant diseases, especially in pediatric patients. In this present study, we aimed to evaluate the retrospective analysis of HLA match and survival between donor and patients who underwent cord blood transplantation through the Istanbul University Faculty of Medicine Bone Marrow Bank. Materials and Methods: In order to research the related factors of umbilical cord blood transplantation in Turkey, 102 cases of umbilical cord blood transplantation performed between 2008 and 2014 were analyzed retrospectively. Cord blood unit search applications were performed through Istanbul University, Istanbul Medical Faculty, Bone Marrow Bank. Results: It was, on average, 45 days between the search request and transplantation (range: 11-113 days). Average age of the patients was 42.48±2.8 (1-192 months), male-to-female ratio was 64/38. The most frequent diseases resulting in transplantation were SCID (n=23), AML (n=13), osteopetrosis (n=10), ALL (n=10) and other diseases. There were 38 (37%) cord blood transplantations with matched HLA-A,-B,-DR; 54 (52%) mismatched for HLA-A or -B antigens; 9 (9%) mismatched for HLA-DR only and 1 (1%) mismatched for HLA-B and -DR antigens. The overall survival rate after HSCT with cord blood was 81.5% (n=31/39). The overall survival rate of the patients with HLA class-I antigens mismatch is 48.1% (26/54), the patients with HLA classII antigens mismatch was 22.2% (2/9) after the HSCT. Conclusion: In conclusion, we found a significant effect in patients undergoing cord blood transplantation with 6/6 HLA matching on overall survival.

Camrelizumab in advanced or metastatic solid tumor patients with microsatellite instability–high/mismatch repair-deficient: Results from an open-label exploratory study.

e15140 Background: PD-1 checkpoint inhibitor has been shown a significant effect in patients (pts) with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumor. Herein, we assessed the efficacy and safety of camrelizumab, a PD-1 checkpoint inhibitor, in advanced or metastatic solid tumor pts with MSI-H/dMMR. Methods: Pts with MSI-H/dMMR solid tumor who had received at least one line of prior systemic chemotherapy were recruited in this single-arm exploratory study. Pts received camrelizumab (200mg, ivd, D1/2W) until disease progression or intolerable toxicity. Response was assessed every 8 weeks. The primary endpoint was objective response rate (ORR) according to RECIST v1.1 criteria. This study was registered at Chinese Clinical Trial Registry, ChiCTR-OIC-17013249. Results: From November 2017 to February 27, 2019, 12 eligible pts were recruited, which covered 9 cancer types. The median age was 58 (range 27-72) years; male/female was 58.3/41.7%. 11 pts were confirmed as MSI-H status, and 1 patient as d-MMR status. All pts were included in efficacy and safety analysis. 2 pts achieved complete response (CR), 6 pts partial response (PR), 4 pts stable disease (SD), yielding the ORR of 66.7% (95% CI: 34.9-90.1), and the disease control rate of 100% (95% CI 73.5-100) at best. What’s more, cancer types of CR pts covered rectal cancer and bladder cancer (1 patient each); PR pts included colon cancer, liver cancer, endometrial cancer, ureteric cancer, intrahepatic cholangiocarcinoma, and small intestine cancer (1 patient each); SD pts contained 3 colon cancer pts and 1 retroperitoneal leiomyosarcoma patient. The overall incidence of adverse incidences (AEs) was 100%. The incidence of Grade ≥3 AEs was 58.3%, which mainly included anemia (16.7%), increased γ-transglutaminase (16.7%), increased alkaline phosphatase (16.7%), increased blood bilirubin (16.7%). As of Oct 30, 2019, 11 pts were still on study medication. Conclusions: Camrelizumab resulted in encouraging objective response and tolerable toxicity in MSI-H/dMMR advanced or metastatic solid tumor. The survival benefits will be further observed. Clinical trial information: ChiCTR-OIC-17013249 .

MP43-06 BAKING SODA EXERTS A SIGNIFICANT ALKALINIZING EFFECT IN PATIENTS WITH UROLITHIASIS WITHOUT INCREASING URINARY CALCIUM EXCRETION

You have accessJournal of UrologyStone Disease: Medical & Dietary Therapy (MP43)1 Apr 2020MP43-06 BAKING SODA EXERTS A SIGNIFICANT ALKALINIZING EFFECT IN PATIENTS WITH UROLITHIASIS WITHOUT INCREASING URINARY CALCIUM EXCRETION Kristina Penniston*, Scott Quarrier, Shuang Li, and R. Allan Jhagroo Kristina Penniston*Kristina Penniston* More articles by this author , Scott QuarrierScott Quarrier More articles by this author , Shuang LiShuang Li More articles by this author , and R. Allan JhagrooR. Allan Jhagroo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000898.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Baking soda (sodium bicarbonate, NaHCO3) has been used for decades as an alkalinizing agent. When taken orally, NaHCO3 increases urine pH and citrate. Despite rising prices of prescriptive urinary alkalinizing agents, urologists may be reluctant to recommend NaHCO3 due to fear of Na-induced hypercalciuria. To assess this potential adverse event, we reviewed our recent clinical experience with baking soda as alkali treatment. METHODS: A convenience sample of patients from our metabolic stone prevention clinic who used baking soda within the past year was assembled from an IRB-approved prospectively maintained database. In addition to taking 1/4 tsp baking soda BID (dissolved in water or other liquid), providing approximately 25 mEq alkali, most patients were counseled to increase intake of bicarbonate precursors from fruits and vegetables. Results from patients’ 24-h urine collections before and during treatment were retrospectively reviewed. The primary outcome was change in urinary calcium (UCa) excretion. Patients were excluded for urine creatinine variation >40% and/or no follow-up urine collection. In order to assess only patients compliant with treatment, those with no increases in either urine citrate or pH and/or 24-h urine Na:Cl ratio <0.9 while on treatment were excluded. RESULTS: Patients (n=21) were mostly male (71%) and were 60±10 y. Urine collections were 9.1±2.1 months apart. Overall, significant increases were observed in urinary citrate excretion (523 to 822 mg/d), pH (5.83 to 6.26), and 24-h urine Na:Cl ratio (1.03 to 1.17); p≤0.003 for all comparisons (paired t-tests). The increase in urinary Na excretion (40±102 mEq) was >3-fold higher than change in Cl excretion, confirming higher Na intake from NaHCO3 vs. dietary salt (NaCl). UCa excretion was not different before and during treatment (191 mg and 217 mg respectively; p=0.18, paired t-test). Before treatment, 4 patients had UCa>250 mg; 2 of these resolved on treatment. Of 5 patients with new-onset hypercalciuria, higher dietary NaCl intake, suggested by higher post-treatment Cl excretion (delta >200 mEq), was deemed to have explained the rise in UCa in a subset of these. CONCLUSIONS: Treatment with baking soda providing 25 mEq alkali daily in patients who achieved increases in urinary citrate excretion and/or urine pH was not associated with higher UCa. Moreover, treatment with baking soda did not exacerbate hypercalciuria in patients with high pre-treatment urine calcium. A prospective trial to confirm these results is currently underway. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e649-e649 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kristina Penniston* More articles by this author Scott Quarrier More articles by this author Shuang Li More articles by this author R. Allan Jhagroo More articles by this author Expand All Advertisement PDF downloadLoading ...

Comparison of Orotracheal versus Nasotracheal Fiberoptic Intubation Using Hemodynamic Parameters in Patients with Anticipated Difficult Airway.

Background:Both nasal and oral routes can be used for fiberoptic intubation. Often it leads to hemodynamic disturbances, which may have a significant effect in patients with limited cardiopulmonary reserve as well as with cerebrovascular diseases.Aims:The aim of the study was to evaluate whether there is a clinically relevant difference between the circulatory responses to oral and nasal fiberoptic intubation.Settings and Design:This was a prospective, randomized, and comparative study.Materials and Methods:In this study, a total of 90 patients with the American Society of Anesthesiologist physical status I and II of either sex in the age group of 18–60 years and having anticipated difficult airway (DA) posted for elective surgery under general anesthesia were randomly allocated into two groups. Patients underwent fiberoptic intubation via either oral or nasal route under sevoflurane anesthesia with bispectral index guidance. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), time taken to intubation, and need of maneuver were measured.Statistical Analysis Used:All the analyses were carried out on SPSS 16.0 version (Inc., Chicago, USA). Mean and standard deviation were calculated. The test of analysis between two groups was done by unpaired t-test.Results:Demographic and DA characteristics were similar in both the groups. Significantly (P < 0.01) lesser alteration in HR, SBP, DBP, and MAP was seen in oral fiberoptic intubation when compared to nasal fiberoptic intubation in the early phase of postintubation. Time taken to intubation was also significantly (P < 0.01) lesser in the oral route compared to the nasal route.Conclusions:Oral fiberoptic intubation causes less hemodynamic alteration and takes less time in comparison to nasal fiberoptic intubation.

Predictive Nomogram for Hyperprogressive Disease During Anti-PD-1/PD-L1 Treatment in Patients With Advanced Non-Small Cell Lung Cancer

Background: Immune-checkpoint inhibitors treatment (ICIs) like anti-PD-1/PD-L1 checkpoint inhibitors has been considered as a standard treatment and produced significant effects in patients with non-small cell lung cancer (NSCLC). However, various studies have reported that anti-PD-1/PD-L1 treatment may lead to the rapid development of tumors called hyperprogressive disease (HPD). It is urgent to determine biomarkers and develop a nomogram for HPD prediction in patients with NSCLC before anti-PD-1/PD-L1 treatment. Methods: This retrospective cohort study included 176 cases (collected from January 1, 2016 to September 31, 2019) for establishing a model of HPD prediction, and 37 cases (collected from October 1, 2019 to April 31, 2020) for validation in the patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors in Sun Yat-sen University Cancer Center. HPD was defined as tumor growth rate (TGR, ≥ 2), or tumor growth kinetics (TGK, ≥ 2) or time to treatment failure (TTF, ≤ 2 months). Univariate and multivariate logistic regression were used to estimate the specified factors associated with HPD. Then the nomogram was developed and validated. Finding: The anti-PD-1/PD-L1 therapy resulted in 9.66% (17/176) incidences of the HPD phenomenon in advanced NSCLC. The overall survival (OS) and progression free survival (PFS) in patients with HPD were significantly shorter than those patients without HPD (OS: 8.82 months [95%CI, 4.91-12.74 months] vs. 15.74 months [95%CI, 13.95-17.53 months], P<0.01; PFS: 2.29 months [95%CI, 1.90-2.69 months] vs. 11.06 months [9.12-12.85 months], P<0.001), respectively. The HPD prediction nomogram included APTT (P<0.01), CD4+CD25+ cells (Treg cells) (P<0.01), the presence of liver metastasis (P<0.05), and more than two metastatic sites (P<0.05). Then patients could be divided into two groups by “HPD score” calculated by the nomogram: “HPD score” = 0.8225× presence of liver metastasis + 0.3954 × more than two metastatic sites + 0.2140 × APTT+0.0873 × Treg cells – 11.2476, with the cut-off point was -1.37 (patients with “HPD score” ≥ -1.37 have high risk of HPD, while patients with “HPD score” < -1.37 have low risk of HPD). The C-index was 0.845, while the area under the curve (AUC) was 0.830 (95% confidence interval [CI]: 0.719-0.950, sensitivity 75.00%, specificity 91.70%). The calibration plot of HPD probability showed an optimal agreement between the actual observation and prediction by nomogram. The good discrimination [AUC, 0.911, 95% CI (0.745-0.950), sensitivity 79.60%, specificity 87.50%] was still exited in the validation cohort. The decision curve analysis showed that the nomogram was more beneficial to patients than the reported biomarkers (including PD-L1, number of metastases, age ≥ 65). Interpretation: The nomogram was constructed with the presence of liver metastasis, more than two metastatic sites, long APTT and high level of Treg cells, which could be used to predict HPD risk. Thus NSCLC patients could receive reasonable management before anti-PD-1/PD-L1 therapy. Funding Statement: This study was funded by National Natural Science Foundation of China (No. 81473233); Science and Technology Program of Guangzhou (No. 201504010038, 201604020079, 201601010008). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Written informed consents were exempted because of retrospective analysis. The Institute Research Ethics Committee of the Sun Yat-Sen University Cancer Center, Guangzhou, China approved this study (IRB No. YB2020-006-01).

Ruxolitinib cream for the treatment of patients with alopecia areata: A 2-part, double-blind, randomized, vehicle-controlled phase 2 study

Thereare currently no treatments for alopecia areata (AA) that are universally effective or approved by the US Food and Drug Administration. Oral ruxolitinib has shown efficacy in extensive AA. Ruxolitinib cream would potentially avoid systemic adverse effects. To assess the efficacy and safety of 1.5% ruxolitinib cream in patients with AA who had at least 25% hair loss by Severity of Alopecia Tool score. This was a 2-part study. Part A was an open-label, 24-week study of 1.5% ruxolitinib cream in patients with 25% to 99% hair loss followed by a 24-week extension period. Part B was a double-blind, vehicle-controlled, 24-week study of 1.5% ruxolitinib cream in patients with 25% to 100% hair loss, followed by a crossover to ruxolitinib cream in the vehicle group for 24weeks and additional treatment time for the ruxolitinib cream group. Although Part A results suggested potential efficacy of 1.5% ruxolitinib cream, there was no significant difference in hair regrowth based on 50% improvement in Severity of Alopecia Tool scores between patients receiving 1.5% ruxolitinib cream and vehicle in part B. There were no significant safety issues with 1.5% ruxolitinib cream. Single strength of ruxolitinib cream. The 1.5% ruxolitinib cream did not have a significant effect in patients with AA.

Effects of Pemetrexed and Docetaxel Combined with Cisplatin in the Treatment of Non-Small Cell Lung Cancer

AbstractPurpose: To compare the clinical effects of pemetrexed and docetaxel combined with cisplatin in the treatment of patients with non-small cell lung cancer. Methods: A total of 58 patients with non-small cell lung cancer who were enrolled between January 2017 and January 2018 were enlisted into a randomized digital table. Twenty-nine patients who have received treatment with combined pemetrexed and cisplatin were assigned to the pemetrexed group whereas for the other 29 patients which were treated with docetaxel and cisplatin combined, were assigned to the docetaxel group to verify the calculated clinical treatment efficiency of the patients with non-small cell lung cancer, SVCAM-1 and alCAM-1 concentrations and to evaluate the quality of life scores of the patients after half a year as well as the incidences of adverse reactions following the treatments provided. Results: The differences in SVCAM-1 and alCAM-1 concentrations, and incidence of adverse reactions in patients with non-small cell lung cancer in the docetaxel group as compared with patients in the pemetrexed group after the treatments were statistically significant (P&lt;0.05) where the calculations were performed with data sets gathered from and between the two groups. Additionally, SVCAM-1 and alCAM-1 concentrations in patients in both pemetrexed group and docetaxel group demonstrated significant differences in concentrations before and after the treatments were provided, P&lt;0.05. The comparative studies of the effects of the treatments on the quality of life scores and clinical treatment efficiency between the two groups after half a year, P&gt;0.05, demonstrated no analytical significance. Conclusion: Both pemetrexed combined with cisplatin and docetaxel in combination with cisplatin as forms of treatments demonstrated significant effects in patients with non-small cell lung cancer. However, based on our study, it was found that the combined treatment involving pemetrexed and cisplatin can further reduce adverse reactions and thus, is worthy of clinical application.Â

Fibrinogen is associated with EGFR mutation status and lymphatic metastasis in non-small cell lung cancer.

In the previous decade, tyrosine kinase inhibitors (TKIs) have demonstrated significant effects in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. However, sufficient tumor tissue for genetic testing cannot always be obtained in clinical settings. The present study evaluated whether fibrinogen may assist in predicting the EFGR mutation status in patients with NSCLC. Between January 2010 to December 2013, 303 patients with NSCLC underwent EGFR mutation testing. Plasma fibrinogen was acquired prior to treatment, and the associations between fibrinogen, EGFR mutation status and clinical features were assessed. A multivariate analysis and a receiver operator characteristic curve analysis were performed to identify the potential value of fibrinogen in predicting EGFR mutation status. The proportion of patients with hyperfibrinogenemia was significantly higher in N2 and N3 stages compared with N0 and N1 stages, 45.2 and 56.5 vs. 29.2 and 36.0%, respectively (P=0.001), and higher in the M1 stage compared with the M0 stage, 47.9 vs. 35.2%, respectively (P=0.025) (Stages according to the American Joint Committee of Cancer, 7th edition). Plasma fibrinogen levels were significantly lower in patients with EGFR mutations compared with the wild-type EGFR gene, 2.95 g/l (range, 0.84 −8.61 g/l) vs. 3.57 g/l (range, 1.38–7.44 g/l), respectively (P<0.001). In the multivariate analysis, logistic regression was utilized and the fibrinogen odds ratio (OR), 2.5, confidence intervals (CI) 1.53–4.51 (P<0.001) and smoking status OR 5.07, CI 3.01–8.53 (P<0.001), for which the area under the curve was 0.75, were revealed to be independent predictive factors. Hyperfibrinogenemia is associated with metastasis of the distant organs, but also metastasis of the lymphatic tissue. In addition, a multivariate model based on fibrinogen and smoking history may be used as a predictive marker of EGFR mutation status in patients with NSCLC.

Reply.

Potential conflict of interest: Nothing to report. Reply: Chen et al. propose a further loop to the IL‐6/STAT3–mIndy axis1 by recalling that interleukin‐6 (IL‐6) is an important player in chronic inflammation–related hepatocellular carcinoma (HCC). Moreover, excellent work in human hepatoma cell lines showed that RNAi‐mediated knockdown of the citrate transporter mINDY was associated with a decrease in cell proliferation, colony formation, and expression of cyclin B1. Metabolically, intracellular levels of citrate, the ATP/ADP ratio, phospholipid content, ATP citrate lyase expression, and mTOR activity decreased, whereas AMPK was activated,2 validating the effect of mIndy deletion in vivo.3 We do not know whether the findings in mice, human hepatoma cell lines, and human liver samples translate into chronic, physiologically significant effects in patients with HCC. Presumably, however, IL‐6 contributes to HCC development together with a complex molecular network, including phospholipids, citrate, AMPK, and mTOR. This part of the argument by Chen et al., therefore, is pertinent and plausible. It is thus reassuring that small molecule inhibitors of mINDY are available,4 because they may serve as interesting tools for the study of mIndy and citrate in hepatic tumorigenesis. Moreover, according to the data discussed above, inhibition of mINDY may hold the potential to be effective in the treatment of HCC; however, this notion needs to be studied further. Thus far, pharmacological inhibition of mINDY has been shown to be effective in improving glucose tolerance and reducing liver fat in diet‐induced obese mice,4 effects that also protect against HCC.

Thalidomide has a significant effect in patients with thalassemia intermedia

ABSTRACTObjective: To investigate the effect of thalidomide in patients with thalassemia intermedia.Methods: We observed the effect of thalidomide in seven patients with thalassemia intermedia requiring blood transfusion. Four of the patients were transfusion-independent, and three patients were transfusion-dependent.Results: For the four transfusion-independent patients, hemoglobin concentration increased significantly (≥2 g/dl) in three and moderately (1–2 g/dl) in one. After 3 months of treatment, hemoglobin concentration increased 3.2 ± 1.2 g/dl compared to pretreatment. Among the three transfusion-dependent patients, transfusion was terminated after one month of treatment in one patient and decreased >50% in the other two patients, accompanied by an increase in the average hemoglobin concentration.Conclusion: Thalidomide had a significant effect in patients with thalassemia intermedia. Further studies of a larger scale and more rigorous design are warranted.