bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful neoadjuvant treatment of EGFR exon 19 deletion combined with TP53 mutation in non-small cell lung cancer using aumolertinib after osimertinib-induced myocardial damage: a case report and literature review
Authors: Zhang Guijuan , Tang Xiaoyuan , Zhang Xingping , Qiu Xingting , Lai Qingwen , Li Jie
Published: February 2023

The development of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) represents a paradigm shift in the treatment of lung cancer with EGFR mutations. Aumolertinib has been shown to be a safe agent in the registry study. However, successful rechallenge with aumolertinib following osimertinib-induced myocardial damage has not been reported. In this article, a case of neoadjuvant therapy for lung adenocarcinoma is retrospectively analyzed, and the relevant literature is reviewed. The patient was diagnosed with stage IIIA lung adenocarcinoma, and genetic testing revealed EGFR exon 19 deletion mutation combined with Tumor Protein p53 (TP53) mutation. The mutation abundance is 33.5 and 14%, respectively. One month after osimertinib treatment, the patient developed myocardial damage, and abnormal indicators such as myocardial enzyme spectrum showed abnormalities and cardiac insufficiency, followed by pulmonary hypertension and pulmonary edema. Aumolertinib was subsequently used for treatment, following which the myocardial enzyme spectrum returned to normal, and the symptoms of bilateral interstitial edema disappeared. In addition to the disappearance of adverse reactions, the therapeutic effect was excellent; the lung lesions and mediastinal lymph nodes were significantly reduced, and the operation was successfully conducted. This is the first report of successful neoadjuvant treatment of EGFR exon 19 deletion combined with TP53 mutation in NSCLC using aumolertinib after osimertinib-induced myocardial damage. The results suggested that aumolertinib had fewer adverse reactions in patients with EGFR exon 19 deletion combined with TP53 mutation, and aumolertinib may be a potential neoadjuvant therapy for stage IIIA lung cancer.
DO DAILY ACTIVITIES AFFECT GAS TAMPONADE‒RETINA CONTACT AFTER PARS PLANA VITRECTOMY?
Authors: Rossi Tommaso , Badas Maria Grazia , Angius Federico , Querzoli Giorgio
Published: February 2023

Purpose:

To calculate the retinal surface alternatively in contact with gas and aqueous because of fluid sloshing during daily activities such as ocular saccade, turning the head, standing up, and being a passenger of a braking car.

Methods:

Fluid dynamics of aqueous and gas tamponade was reproduced using computational methods using the OpenFOAM open-source library. The double-fluid dynamics was simulated by the volume of fluid method and setting the contact angle at the aqueous–gas–retina interface.

Results:

Sloshing increased the retinal surface in contact with aqueous by 13% to 16% regardless of fill rate and standing up determined the largest area of wet retina, followed by car braking, head rotation, and ocular saccade (P < 0.001). All activities except the ocular saccade determined a significant increase in the surface of retina in contact with the aqueous (P < 0.005). Car braking induced the highest shear stress (6.06 Pa); standing up determined the highest specific impulse and saccade the lowest.

Conclusion:

Daily activities instantaneously reduce the amount of retina consistently in contact with gas tamponade and increase shear stress giving aqueous a potential access to the subretinal space regardless of patients' compliance.
The mediating effect of mindfulness on demoralization syndrome and quality of life of thyroid cancer patients: A correlational study
Authors: YuYu Li , Shan Zhao , JingJun Peng
Published: February 2023

Demoralization syndrome is prevalence among cancer patients in China. However, little research has examined how demoralization syndrome is associated with quality of life (QOL). The aims of this study were to investigate the relationship between mindfulness state, demoralization syndrome and QOL of thyroid cancer patients, and explore the mediating effect of mindfulness on demoralization syndrome and QOL. A correlational cross-sectional study was performed using an online questionnaire. The study was conducted from July to October 2022 among 310 thyroid cancer patients. General information questionnaire, the Demoralization Scale, Five Facet Mindfulness Questionnaire, short form health survey questionnaire were used for investigation. Calculations were performed using SPSS Statistics, version 25. Descriptive statistics, correlation, and process plug-in mediation effect analyses were used to analyze the data. A total of 310 valid questionnaires were finally recovered. The Five Facet Mindfulness Questionnaire score of 310 patients was (120.80 ± 16.57), Demoralization Scale score was (12.49 ± 4.73), short form health survey questionnaire score was (146.15 ± 28.46). Mindfulness played a partial mediating role between demoralization syndrome and QOL of thyroid cancer patients, and the mediating effect accounted for 68.57% of the total effect. Demoralization syndrome can influence QOL through mindfulness state. Measures are needed to increase the QOL of thyroid cancer patients by developing mindfulness programs to decrease their demoralization syndrome.
Daridorexant for the treatment of insomnia disorder: A systematic review and meta-analysis of randomized controlled trials
Authors: Jiang Feiyu , Li Hang , Chen Yanting , Lu Haifeng , Ni Jianqiang , Chen Gang
Published: February 2023

Background:

Daridorexant is a novel dual orexin receptor antagonist that has shown efficacy as a treatment for insomnia in multiple randomized clinical trials. However, the efficacy and safety of daridorexant for treatment of insomnia disorder has not been characterized comprehensively in the literature. Therefore, we performed a meta-analysis of available studies. We performed a meta-analysis to systematically evaluate the efficacy and safety of daridorexant for treatment of insomnia disorder.

Methods:

MEDLINE, Embase, Cochrane Library, and Clinicaltrials.gov for randomized controlled trials were systematically searched up to February 2022. Relative risk and standard mean difference were used to evaluate clinical outcomes.

Results:

We pooled 2271 patients from 4 randomized clinical trials, and evaluated efficacy endpoints. We found that 50 mg of daridorexant was superior to placebo for 4 efficacy outcomes including wake time after sleep onset, latency to persistent sleep, subjective total sleep time, and Insomnia Daytime Symptoms and Impacts Questionnaire domain score (P < .05). In addition, there were no significant differences (P > .05) in adverse events between daridorexant and placebo.

Conclusions:

Different dosages of daridorexant were tested for treatment of insomnia; however, 5 and 10 mg are not available because of issues of suboptimal effectiveness. Daridorexant showed better efficacy and safety for treatment of insomnia disorder at doses of 25 and 50 mg.
Press needle for aspiration pneumonia prevention in older adults: Study protocol for a randomized double-blind placebo-controlled trial
Authors: Kaneko Soichiro , Kikuchi Akiko , Takayama Shin , Arita Ryutaro , Ohsawa Minoru , Kamiya Tetsuharu , Ishii Tadashi
Published: February 2023

Background:

Pneumonia is the fifth most common cause of death among the Japanese population, with 97% of the deaths occurring among older adults aged ≥65 years. The incidence ratio of aspiration pneumonia is high among the older adults. Therefore, its prophylaxis is important in geriatric medicine. In our previous studies, we reported that stimulation of acupoints at stomach meridian 36 and kidney meridian 3 of the lower limbs with a press needle improved the swallowing function of patients with dysphagia. Improvements in swallowing function may prevent aspiration pneumonia. This study aims to investigate the protective efficacy of press needle stimulation in the lower limbs for aspiration pneumonia.

Methods/design:

This is a multicenter, randomized, double-blind, placebo-controlled trial. A total of 140 patients with cerebrovascular disorder and a history of aspiration pneumonia will be recruited from 6 centers and randomly assigned to either the real or sham press needle group in a 1:1 ratio. The press needle will be replaced twice a week. The treatment will be administered bilaterally at acupoints stomach meridian 36 and kidney meridian 3. The primary outcome is the frequency of aspiration pneumonia onset. The secondary outcome is the improvement of the latent time of the swallowing reflex. The study period is of 12-month. The primary outcome will be evaluated throughout the study period, while the secondary outcomes will be assessed at baseline, 1st month, 6th month, and at the end of the investigation period.

Discussion:

This study will evaluate the effects of press needle on the prevention of aspiration pneumonia and the improvement of swallowing function in patients. The results of this study will help support the prophylaxis of aspiration pneumonia.
Pain management with epidural catheter and epidural analgesia after spinal dorsal instrumentation of lumbar spine
Authors: Hamed Motaz , Asoglu Harun , Lampmann Tim , Winkelmann Lena Marie , Salemdawod Abdallah , Müller Martin , Vatter Hartmut , Banat Mohammed , Eichhorn Lars
Published: February 2023

Spinal dorsal instrumentation (SDI) is an established treatment for degenerative spinal diseases. Adequate and immediate postoperative pain control is important for patient recovery and may be compromised by uncertainty about its efficacy and concern about early postoperative surgical complications or adverse events. The aim of the current study was to compare the use of epidural analgesia (EA) with systemic analgesia (SA) as regards pain reduction and early postoperative complications after SDI. Pain management with epidural or systemic analgesia in patients undergoing SDI by posterior approach between January 2019 and July 2020 was evaluated by clinical functional testing, measuring total opioid amounts used, and evaluating numerical rating scale values 24 and 96 hours postoperatively. The following were also monitored: demographic data, number of affected segments, length of hospital stay, inflammatory markers (leukocytes and serum C-reactive protein), early postoperative surgical complication rates, and adverse events. In total 79 patients were included (33 in the EA and 46 in the SA group). The SA group had significantly lower numerical rating scale values at days 1 to 4 after surgery (P ≤ .001) and lower cumulative opioid use than the EA group (P < .001). We found no difference in infection parameters, length of hospital stay or surgery-related complication rates. Our data demonstrate that epidural anesthesia was inferior to an opioid-based SA regime in reducing postoperative pain in patients undergoing spinal surgery. There is no benefit to the use of epidural catheters.
Effect of individualized comfortable nursing on prognosis of vacuum sealing drainage in patients with orthopedic trauma
Authors: Xie Huifang , Guo Zhaodi , Cao Qin , Ye Yuan , Chen Li , Luo Na
Published: February 2023

To explore the effect of individualized comfortable nursing on prognosis of vacuum sealing drainage (VSD) in patients with orthopedic trauma. 110 patients with orthopedic trauma VSD were randomly divided into the control group and the observation group, with 55 patients in each group receiving routine care and comfortable care. The wound healing time, visual analog scale, quality of life score, the level of inflammatory factors, the incidence of complications, and patient satisfaction were compared between the 2 groups. The average time of wound healing in the observation group was significantly lower than that in the control group (P < .01). The satisfaction rate in the observation group was significantly higher than that in the control group (P = .029). Meanwhile, the results showed that visual analog scale and quality of life scores in the observation group was significantly improved than that of the control group after receiving intervention (P < .05). After receiving intervention, the levels of TNF-α and IL-6 of patients in both groups were decreased, and the levels of TNF-α and IL-6 in the observation group were significantly decreased than those in the control group. Moreover, the incidence rate of adverse reaction in the observation group was significantly lower than that in the control group (P < .01). Comfortable nursing can reduce the wound healing time, the postoperative pain level, the incidence of complications, and improve patient satisfaction, which is of great significance for the prognosis of VSD in patients with orthopedic trauma.
Factors predictive of functional outcomes and quality of life in patients with fragility hip fracture: A retrospective cohort study
Authors: Kang Mun Jeong , Kim Bo Ryun , Lee Sang Yoon , Beom Jaewon , Choi Jun Hwan , Lim Jae-Young
Published: February 2023

To determine the predictors of functional outcomes and quality of life (QoL) of patients who were surgically treated for fragility hip fracture. This was a retrospective cohort study performed in the 3 tertiary rehabilitation facilities. A total of 165 patients who had undergone surgery for fragility hip fracture were followed up to 6 months postoperatively. The factors expected to be related to the functional outcomes and QoL at 6 months post-surgery were as follows: baseline demographics, fracture site, operation type, fall characteristics including fall location and fall direction, comorbidities, and initial functional status. The following were comorbidities: hypertension, diabetes mellitus, dementia, cerebrovascular accident, and osteoporosis. Functional outcome and QoL measures were represented using the Koval grade, functional ambulatory category (FAC), Berg balance scale, 4-m walking speed test, the Korean version of Mini-Mental State Examination, EuroQol 5-dimension (EQ-5D) questionnaire, the Korean version of Modified Barthel Index, and the Korean version of instrumental activities of daily living (K-IADL). For all tests, each patient was assessed immediately after transfer and at 6 months post-surgery. Multivariable regression analyses adjusting for factors mentioned above were as follows. Old age led to a significantly less favorable outcome on FAC and K-IADL at 6 months. Intertrochanteric fracture had a significantly positive impact on Koval at 6 months compared to femur neck and intertrochanteric fractures. Total hip replacement arthroplasty and bipolar hemiarthroplasty had a significantly positive impact on EQ-5D and FAC at 6 months respectively compared to other operation types. Fall characteristics didn’t reveal any significant impact on functional outcomes and QoL. Patients with hypertension and diabetes mellitus had a significantly negative outcome on EQ-5D and K-IADL respectively. Among initial assessments of function and QoL, initial 4-m walking speed test, Korean version of Mini-Mental State Examination, K-IADL, and Korean version of Modified Barthel Index were independent predictors of function and QoL at 6 months. This study confirmed that age, fracture site, operation type, comorbidities, and initial physical and cognitive function significantly influenced recovery of function and QoL at 6 months in patients with fragility hip fractures.
Prospective evaluation of radiographic manifestations of tuberculosis in relationship with CD4 count in patients with HIV/AIDS
Authors: Frey Vanessa , Phi Van Valerie Doan , Fehr Jan S , Ledergerber Bruno , Sekaggya-Wiltshire Christine , Castelnuovo Barbara , Kambugu Andrew , Bauer Max , Eberhard Nadja , Martini Katharina , Frauenfelder Thomas
Published: February 2023

A major risk factor to develop active tuberculosis (TB) is the infection with the human immunodeficiency virus (HIV). Chest radiography is the first-line imaging modality used to rule out TB. Coinfected individuals present often with atypical imaging patterns, due to the immunosuppression caused by the virus, making diagnosis difficult. In this prospective observational study 268 TB and HIV coinfected patients were included. During a follow-up period of 24 weeks, the predominant patterns on chest radiography were analyzed and compared to the cluster of differentiation 4 (CD4) count under antiretroviral and anti-TB therapy. Patients with low CD4 counts (<200 cells//µL) showed more often lymphadenopathy (62% vs 38%;P = .08) and a miliary pattern (64% vs 36%;P = .04) but less likely cavitation (32% vs 68%;P = .008) or consolidation (47% vs 63%;P = .002) compared to individuals with higher CD4 counts. Over the follow-up period, partial response to therapy was the most frequent radiological evolution (62%), mainly accompanied by an increase of CD4 cells (92%). Patients with a decrease in CD4 count mostly presented with a worsening in radiological findings (53%). Radiographic TB manifestation correlated with the immune status of patients coinfected with HIV. Low CD4 counts often showed atypical manifestation.
Gene mutations in the PI3K/Akt signaling pathway were related to immune thrombocytopenia pathogenesis
Authors: Ruan Jing-Shu , Sun Rui-Jie , Wang Jin-Ping , Sui Xiao-Hui , Qu Hui-Ting , Yuan Dai , Shan Ning-Ning
Published: February 2023

Background:

Immune thrombocytopenic (ITP) is an autoimmune bleeding disease with genetic susceptibility. Twenty newly diagnosed active primary ITP patients who had not been treated with glucocorticosteroids, immune globulin or immunosuppressants prior to sampling were enrolled in this study. Bone marrow blood mononuclear cells were used for whole exome sequencing to further elucidation the variant genes of ITP.

Methods:

High-molecular-weight genomic DNA was extracted from freshly frozen bone marrow blood mononuclear cells from 20 active ITP patients. Next, the samples were subjected to molecular genetic analysis by whole-exome sequencing, and the results were confirmed by Sanger sequencing. The signaling pathways and cellular processes associated with the mutated genes were identified with gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses.

Results:

The results showed that there were 3998 missense mutations involving 2269 genes in more than 10 individuals. Unique genetic variants including phosphatase and tensin homolog, insulin receptor, and coagulation factor C homology were the most associated with the pathogenesis of ITP. Functional analysis revealed these mutation genes mainly affect Phosphatidylinositol 3 kinase/serine/threonine kinase B signaling pathways (signal transduction) and platelet activation (immune system).

Conclusion:

Our finding further demonstrates the functional connections between these variant genes and ITP. Although the substantial mechanism and the impact of genetic variation are required further investigation, the application of next generation sequencing in ITP in this paper is a valuable method to reveal the genetic susceptibility.
Wilson disease in pregnancy: A case series
Authors: Xiong Xiali , Wei Hong , Zhu Yunxia , Zhou Xin , Zhao Zhiqiang , Chen Qiang
Published: February 2023

Rationale:

Hepatolenticular degeneration, also known as Wilson disease (WD), is an autosomal recessive inherited disease characterized by copper metabolism, which has complex clinical manifestations, and mainly including liver and nervous system lesions. Pregnancy combined with WD is extremely harmful to mothers and children, with high miscarriage rates, and premature birth rates and perinatal mortality.

Patient concerns:

Here we introduced the basic information of 4 pregnant women with WD. The first pregnant woman had a 16-year history of WD, stopped taking penicillamine 1 year before pregnancy. The second woman had a 3-year history of WD and was taking penicillamine regularly, unintended pregnancy occurred 1 month after stopping the drug. The third woman had a history of WD for 5 years with penicillamine treatment. The 4th woman was found to have WD due to repeated missed miscarriage with abnormal liver function, after which penicillamine was regularly taken. Fortunately, she was pregnant again a year later.

Diagnoses:

The pregnant women in case 1 and case 2 were diagnosed with decompensated cirrhosis with coagulation dysfunction during pregnancy. The pregnant woman in case 3 was found to have liver cirrhosis by ultrasound, and the pregnant woman in case 4 did not have liver abnormalities during pregnancy.

Interventions:

The pregnant woman in case 1 began to take copper-removing drugs and take a low-copper diet after finding the aggravation of the disease in the early stage of pregnancy, and had good compliance during pregnancy. The pregnant woman in case 2 had poor compliance during pregnancy and did not receive any treatment. The pregnant woman in case 3 refused to use copper elimination drugs during pregnancy, but took a low copper diet. The pregnant woman in case 4 had good compliance during pregnancy, and she was treated with drugs and low copper diet during the whole pregnancy.

Outcomes:

Three of the four pregnant women got a healthy baby but premature, and only the pregnant woman in case 2 had spontaneous abortion at 25 weeks.

Lessons:

After comprehensive monitoring and multidisciplinary management of professional medical staff before and after pregnancy, WD pregnant women still have the opportunity to obtain a better pregnancy outcome and improve quality of life.
Breast cancer knowledge in Lebanese females with positive family history
Authors: El Maouchi Paul , Fakhreddine Omar , Shmoury Abdel Hadi , El Zoghbi Mohamad , Chamseddine Nathalie , Abou Zeidane Reine , Amhaz Ghid , Charafeddine Maya , Kazarian Houry , Assi Hazem I.
Published: February 2023

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer-related death worldwide. Positive family history increases the likelihood of developing this disease. As late-stage presentation and poor survival rates are associated with a lack of knowledge about breast cancer and its screening methods, this study aimed to evaluate the knowledge of Lebanese women with first-degree relatives who were diagnosed with breast cancer. In this cross-sectional study, 200 women with a positive family history accompanying their relatives to oncology clinics or the infusion center at the American University of Beirut Medical Center, completed an online survey after institutional review board approval was granted. Demographic information and answers to questions related to breast cancer risk factors, warning signs, and screening techniques were collected and analyzed using descriptive statistics and chi-square tests. Eighty-one percent of the study participants agreed that a history of breast cancer is associated with a higher disease risk. The smaller portions were aware of other potential risk factors, such as hormone replacement therapy, alcohol consumption, late menopause, early menarche, and overweight and sedentary lifestyles. Also, 93% to 96.5% of the participants recognized breast self-examination and mammography as useful tools for early detection. Furthermore, younger participants who reached university level and were employed had more insights into breast cancer. Breast cancer knowledge and early diagnosis are key elements in preventing late presentations and reducing the associated morbidity and mortality. Further educational and awareness campaigns should be conducted in Lebanon to improve women knowledge of breast cancer.
Lung ultrasound score-based assessment of postoperative atelectasis in obese patients according to inspired oxygen concentration: A prospective, randomized-controlled study
Authors: Min Won Kee , Jin Sejong , Choi Yoon Ji , Won Young Ju , Lee Kaehong , Lim Choon-Hak
Published: February 2023

Background:

According to a recent meta-analysis, in patients with a body mass index (BMI) ≥ 30, a high fraction of inhaled oxygen (FiO2) did not increase postoperative atelectasis. However, a high FiO2 generally increases the risk of postoperative atelectasis. Therefore, this study aimed to evaluate the effect of FiO2 on the development of atelectasis in obese patients using the modified lung ultrasound score (LUSS).

Methods:

Patients were assigned to 4 groups: BMI ≥ 30: group A (n = 21) and group B (n = 20) and normal BMI: group C (n = 22) and group D (n = 21). Groups A and C were administered 100% O2 during preinduction and emergence and 50% O2 during anesthesia. Groups B and D received 40% O2 for anesthesia. The modified LUSS was assessed before and 20 min after arrival to the postanesthesia care unit (PACU).

Results:

The difference between the modified LUSS preinduction and PACU was significantly higher in group A with a BMI ≥ 30 (P = .006); however, there was an insignificant difference between groups C and D in the normal BMI group (P = .076).

Conclusion:

High FiO2 had a greater effect on the development of atelectasis in obese patients than did low FiO2; however, in normal-weight individuals, FiO2 did not have a significant effect on postoperative atelectasis.
Giant cell tumor of bone with H3F3B mutation: A case report
Authors: Wu Ruinuan , Wu Xikang , Weng Xin , Xiu Yingjie , Xu Gang , Liu Xiajing , Liu Xia
Published: February 2023

Rationale:

Giant cell tumor of bone is a locally aggressive and rarely metastasizing neoplasm that typically affects the ends of long bones or the axial skeleton of young to middle-aged adults. As many as 69% to 100% of giant cell tumors harbor H3F3A gene mutations, while H3F3B gene mutations have rarely been reported.

Patient concerns:

A 53-year-old male patient who underwent right distal femoral tumor resection.

Diagnoses:

Preoperative CT plain scan indicated giant cell tumor of bone with pathological fracture. Laboratory findings were as follows: serum calcium was 2.23 mmol/L (reference range: 2.1–2.55 mmol/L) and serum phosphorus was 1.35 mmol/L (reference range: 0.81–1.45 mmol/L).

Interventions:

The histological morphology showed the typical features of a conventional GCT. The immunoprecipitation analysis results were as follows: H3.3G34W(−), H3.3G34R(−), H3.3G34V(−), and H3K36M(−). Sanger sequencing showed that the H3F3A and H3F3B gene mutations were wild type. The high-throughput gene sequencing results revealed the H3F3B gene mutations H3.3p.Gly35Trp and H3.3p.Val36Leu.

Outcomes:

The patient was stable with no recurrence in 12 months follow-up.

Lessons:

Giant cell tumor of bone with H3F3B gene mutations is extremely rare. In the pathological diagnosis of bone tumors, we need to analyze clinical presentation, imaging features, histology, immunophenotype, and cytogenetic/molecular alterations, in order to get a correct diagnosis.
Cochlear implantation in a patient with congenital microtia, cochlear hypoplasia, venous anomalies of the temporal bone and laryngomalacia: Challenges and surgical considerations
Authors: Gao Xue , Zhao Juan , Li Guan-Hua , Wang Xi , Wang Wei , Liu Xing , Liu Min , Guo Meng-Meng , Wang Zhen-Dong , Lu Ya-Yan , Li Jia , Feng Yong , Yang Kun , Xu Jin-Cao , Dai Pu
Published: February 2023

Rationale and patient concerns:

Congenital hearing loss is often caused by an inner ear malformation, in such cases, the presence of other anomalies, such as microtia, and venous anomalies of the temporal bone and laryngomalacia makes it challenging to perform cochlear implantation surgery.

Diagnoses:

This study reports the case of a 28-month-old girl with congenital profound hearing loss, laryngomalacia, and malformed inner ear, who received cochlear implantation surgery. The bony structure, vessels and nerves were first assessed through magnetic resonance imaging and computed tomography before exploring the genetic basis of the condition using trio-based whole exome sequencing. Perioperative evaluation and management of the airway was then performed by experienced anesthesiologist, with the surgical challenges as well as problems encountered fully evaluated.

Interventions:

Cochlear implantation was eventually performed using a trans-mastoid approach under uneventful general anesthesia.

Outcomes:

Due to the small size of the cochlea, a short electrode FLEX24 was inserted through the cochleostomy.

Lessons:

Considering the high risk of facial nerve injury and limited access to the cochlea when patients present significant bony and venous anomalies, cochlear implantation in such patients require careful preoperative evaluation and thoughtful planning. In these cases, airway assessment, magnetic resonance venography, magnetic resonance arteriography, and magnetic resonance imaging and computed tomography can be useful to minimize the risks. Intraoperative facial nerve monitoring is also recommended to assist in the safe location of facial nerve.
Missed diagnosis of lissencephaly after prenatal diagnosis: A case report
Authors: Liu Mengna , Liu Xiao , Wu Jiebin , Sha Jing , Zhai Jingfang , Zhang Bei
Published: February 2023

Rationale:

Lissencephaly (LIS) is a rare and serious cortical malformation characterized by a smooth or nearly smooth brain surface. With the progress of molecular genetics, platelet-activating factor acetylhydrolase brain isoform Ib is the most frequent type during the fetal period. Here, we report an infant with LIS who was missed although undergoing prenatal diagnosis. We aim to share our experiences and lessons.

Patient concerns:

A 2-month-old male infant presented recurrent convulsions. Karyotype and copy number variation sequencing were conducted to be normal at the 23-week gestation because of bipedal varus and ventricular septal defect (2.3 mm). After birth, he suffered from epilepsy confirmed by video electroencephalogram exam, meanwhile, computed tomography and magnetic resonance imaging revealed pachygyria. The infant was diagnosed with LIS carrying a de-novo mutation c.817 C > T (p.Arg273 Ter,138) in exon 8 of platelet-activating factor acetylhydrolase brain isoform Ib (NM_000430) detected by whole-exome sequencing.

Diagnoses:

Based on the clinical characteristics, imaging, and genetic test findings, the infant was diagnosed with LIS.

Interventions:

The patient was treated with topiramate and dose was adjusted according to the seizure frequency.

Outcomes:

The infant had recurrent seizures. The muscle tone of his extremities increased, and he could not look up or turn over actively at the age of 6 months.

Lessons:

Comprehensive evaluation of a multi-disciplinary team should be recommended for patients with epilepsy and cerebral hypoplasia. Individuals with LIS during the fetal period might be missed due to atypical features. In fetuses with structural abnormalities, if karyotype and copy number variation sequencing are both normal, whole-exome sequencing may be an effective complementary means to detect pathogenic variants.
TCF7L2, CASC8, and GREM1 polymorphism and colorectal cancer in south-eastern Romanian population
Authors: Mitroi Anca Florentina , Leopa Nicoleta , Dumitru Eugen , Dumitru Andrei , Tocia Cristina , Popescu Ioana , Mitroi Adrian , Popescu Răzvan Cătălin
Published: February 2023

Colorectal cancer (CRC) is a heterogeneous disease with an increasing trend and with multiple epigenetic alterations and different molecular features, a major cause of mortality and morbidity. The Wnt/β-Catenin pathway is involved in multiple aspects of cell dynamics, architecture of developing gastrointestinal tissues, and intestinal tissue homeostasis in adults, but its aberrant activity plays an important role in every aspect of colorectal carcinogenesis. The aim of our study was to investigate the association of the TCF7L2 rs7903146, CASC8 rs6983267, and Gremlin1 (GREM1) rs16969681 polymorphism in patients with CRC without other pathologies. A case-control study conducted on 31 patients diagnosed with CRC and 30 healthy controls age and sex-matched with the patients. Real time PCR was used to determine the genotypes of rs7903146, rs698267, rs1696981. We observed no association between rs6983267 and rs16969681 polymorphism and risk of CRC and low association between TCF7L2, rs7903146, polymorphism and risk of CRC. The recessive model of the TCF7L2 rs7903146 had an OR of 1.6 (95% CI 0.058–4.414, P < .05) which means that TT genotype increased the risk and possibility of development of CRC. Our study did not confirm a significant association between TCF7L2 rs7903146, CASC8 rs6983267, and GREM1 rs16969681 with CRC, but emphasizes the possibility of existence of a high risk of CRC development in patients with TT genotype of rs7903146.
Pneumatosis Intestinalis in Children With Intestinal Failure: The Result of Intestinal Stress From Enteral Feeding?
Authors: Reppucci Marina L. , Nolan Margo M. , Cooper Emily , Gallagher Lauren T. , Diaz-Miron Jose , Somme Stig , Soden Jason , Gumer Lindsey , Acker Shannon N.
Published: February 2023

Objective:

The incidence and significance of pneumatosis intestinalis (PI) in children with a diagnosis of intestinal failure is not well understood. The aim of this study was to identify clinical and anatomical factors associated with the imaging findings of PI in patients with intestinal failure.

Methods:

We performed a retrospective review of all children with a diagnosis of intestinal failure at Children’s Hospital Colorado between January 2019 and April 2022. Patients were stratified and compared based on the incidence of PI on abdominal imaging. Differences were compared using 2-sample Wilcoxon tests, chi-square, or Fisher exact tests.

Results:

There were 111 patients identified with a diagnosis of intestinal failure and 30.6% (34) developed at least 1 instance of PI. There were no differences in etiology of intestinal failure or anatomy between those who developed PI and those who did not. Patients who developed PI, were less likely to be on total parental nutrition (60.6% vs 98.6%, P < 0.001) and more likely to be receiving any form of enteral feeds (87.9% vs 66.2%, P = 0.035) or tube feeds (75.8% vs 44.2%, P = 0.0045). Of the children with PI, 30.3% (10) were undergoing an enteral feed advancement at time of PI development. Three patients with PI underwent laparotomy for PI treatment, 2 of which were negative laparotomies.

Conclusions:

The development of PI in children with intestinal failure is likely a benign finding. It is associated with enteral feeding and may be due to increased intestinal stress.
Demonstrating the Value of the Clinical Nurse Specialist
Authors: Fischer-Cartlidge Erica , Hoffman Megan
Published: February 2023

Purpose/Objectives

The purpose of this article is to provide a guide to identifying measurements of value and how to calculate different types of return on investment (ROI). Exemplars of clinical nurse specialist (CNS) work efforts with ROI will be presented.

Description of the Project/Problem

The CNS is the oldest advanced practice role; however, the role can be vague, making it difficult to articulate the value of the CNS in the organization. Functioning in 3 spheres of impact, the CNS can easily impact practice; however, demonstrating the value of this work is not always on top of mind and is rarely taught in academic programs.

Outcome

This article describes the difference between revenue generation, cost savings, and cost avoidance, as well as various structural, process, and outcome measures that can be used to calculate ROI. Resources available for performing ROI calculations will be described and shared.

Conclusion

Distributing work across the 3 spheres creates various opportunities for the CNS to demonstrate value; however, the CNS must be able to articulate that value to the organization. Developing the skill set to consistently identify metrics can be challenging; however, it is critical to the ongoing success and future of the CNS role. Utilizing these metrics to demonstrate the value and then disseminating the outcomes of these contributions will continue to promote the value of the CNS in the future.
HIV-PASS (Pain and Sadness Support): Randomized Controlled Trial of a Behavioral Health Intervention for Interference Due to Pain in People Living With HIV, Chronic Pain, and Depression
Authors: Uebelacker Lisa A. , Pinkston Megan M. , Busch Andrew M. , Baker Jason V. , Anderson Bradley , Caviness Celeste M. , Herman Debra S. , Weisberg Risa B. , Abrantes Ana M. , Stein Michael D.
Published: February 2023

Objective

This study aimed to determine whether HIV-Pain and Sadness Support (HIV-PASS), a collaborative behavioral health intervention based on behavioral activation, is associated with decreased pain-related interference with daily activities, depression, and other outcomes in people living with HIV.

Methods

We conducted a three-site clinical trial (n = 187) in which we randomly assigned participants to receive either HIV-PASS or health education control condition. In both conditions, participants received seven intervention sessions, comprising an initial in-person joint meeting with the participant, their HIV primary care provider and a behavioral health specialist, and six, primarily telephone-based, meetings with the behavioral health specialist and participant. The intervention period lasted 3 months, and follow-up assessments were conducted for an additional 9 months.

Results

Compared with health education, HIV-PASS was associated with significantly lower pain-related interference with daily activities at the end of month 3 (our primary outcome; b = −1.31, 95% confidence interval = −2.28 to −0.34). We did not observe other differences between groups at 3 months in secondary outcomes that included worst or average pain in the past week, depression symptoms, anxiety, and perceived overall mental and physical health. There were no differences between groups on any outcomes at 12 months after enrollment.

Conclusions

A targeted intervention can have positive effects on pain interference. At the end of intervention, effects we found were in a clinically significant range. However, effects diminished once the intervention period ended.

Trial Registration

ClinicalTrials.gov NCT02766751.
Resistance-minimizing strategies for introducing a novel antibiotic for gonorrhea treatment: a mathematical modeling study
Authors: Reichert E , Yaesoubi R , Rönn MM , Gift TL , Salomon JA , Grad YH
Published: February 2023

Background

Gonorrhea is a highly prevalent sexually transmitted infection and an urgent public health concern due to increasing antibiotic resistance. Only ceftriaxone remains as the recommended treatment in the U.S. The prospect of approval of new anti-gonococcal antibiotics raises the question of how to deploy a new drug to maximize its clinically useful lifespan.

Methods

We used a compartmental model of gonorrhea transmission in the U.S. population of men who have sex with men to compare strategies for introducing a new antibiotic for gonorrhea treatment. The strategies tested included holding the new antibiotic in reserve until the current therapy reached a threshold prevalence of resistance; using either drug, considering immediate and gradual introduction of the new drug; and combination therapy. The primary outcome of interest was the time until 5% prevalence of resistance to both the novel drug and to the current first-line drug (ceftriaxone).

Findings

The reserve strategy was consistently inferior for mitigating antibiotic resistance under the parameter space explored. The reserve strategy was increasingly outperformed by the other strategies as the probability ofde novoresistance emergence decreased and as the fitness costs associated with resistance increased. Combination therapy tended to prolong the development of antibiotic resistance and minimize the number of annual gonococcal infections.

Interpretation

Our study argues for rapid introduction of new anti-gonococcal antibiotics, recognizing that the feasibility of each strategy must incorporate cost, safety, and other practical concerns. The analyses should be revisited once robust estimates of key parameters–likelihood of emergence of resistance and fitness costs of resistance for the new antibiotic–are available.

Funding

U.S. Centers for Disease Control and Prevention (CDC), National Institute of Allergy and Infectious Diseases
Large-scale empirical identification of candidate comparators for pharmacoepidemiological studies
Authors: Bohn Justin , Gilbert James P. , Knoll Christopher , Kern David M. , Ryan Patrick B.
Published: February 2023

Objectives

The new user cohort design has emerged as a best practice for the estimation of drug effects from observational data. However, despite its advantages, this design requires the selection and evaluation of comparators for appropriateness, a process which can be challenging. In this paper, we introduce an empirical approach to rank candidate comparators in terms of their similarity to a target drug in high-dimensional covariate space.

Methods

We generated new user cohorts for each RxNorm ingredient in five administrative claims databases, then extracted aggregated pre-treatment covariate data for each cohort across five clinically oriented domains. We formed all pairs of cohorts with ≥ 1,000 patients and computed a scalar similarity score, defined as the average of cosine similarities computed within each domain, for each pair. Ranked lists of candidate comparators were then generated for each cohort.

Results

Across up to 1,350 cohorts forming 922,761 comparisons, drugs that were more similar in the ATC hierarchy had higher cohort similarity scores. The most similar candidate comparators for each of six example drugs corresponded to alternative treatments used in the target drug’s indication(s), and choosing the top-ranked comparator for randomly selected drugs tended to produce balance on a majority of covariates. This approach also ranked highly those comparators chosen in high quality published new user cohort design studies.

Conclusion

Empirical comparator recommendations may serve as a useful aid to investigators and could ultimately enable the automated generation of new user cohort design-derived evidence, a process that has previously been limited to self-controlled designs.

KEY POINTS

Empirical comparator recommendations based on similarity to a target cohort’s covariate profile can aid investigators in study design and align with subject matter knowledge and published literature.
BIOMARKERS OF AIRWAY INFLAMMATION AND ASTHMA SYMPTOM CONTROL IN CHILDREN
Authors: Alieva J.S. , Furman E.G. , Khuzina E.A. , Abdrakhmanova S.T. , Ponomareva M.S. , Sheludko V.S. , Sokolovsky V.L.
Published: February 2023

INTRODUCTION

Bronchial asthma (BA) is a heterogeneous pulmonary disease with various phenotypes based on detection of multiple biomarkers. However, most of the biomarkers are still experimental and present limitations for clinical practice.

OBJECTIVE

The purpose of this study was to investigate the relationship between the level of the available T2-inflammatory biomarkers in childhood with poor asthma control and features of asthma management.

MATERIAL AND METHODS

The study comprised 100 patients aged 5–17 years (median age 13 years) with an established bronchial asthma diagnosis. The level of asthma control of each patient was assessed by the Asthma Control Test (ACT and C-ACT) and the Composite Asthma Severity Index (CASI). T2-inflammatory biomarkers of the mucous membranes of the respiratory tract include total immunoglobulin E (IgE total) levels, peripheral blood eosinophil levels, fractional exhaled nitric oxide (FeNO) and a nasal smear eosinophil count. A measure of association was determined by standard statistical methods for data analysis.

RESULTS

Despite the prescribed basic therapy, the majority of children do not achieve adequate asthma symptom control. This research revealed that 43% of patients had at least one or more elevated markers of T2-inflammation. High levels of IgE total, increased levels of blood eosinophils (≥400 cells/µL), as well as high FeNO values (≥ 20 ppb) prevail in children with partially controlled and uncontrolled asthma. The most significant biomarker of poor asthma control in children is the total serum IgE concentration ≥ 100 IU/ml. In addition, a significant positive correlation was found between peripheral blood eosinophil levels and the ACT/C-ACT scores (r=0.287, p=0.0039).

CONCLUSION

Allergic asthma in children is typically associated with Th2-lymphocytes predominance and eosinophilic airway inflammation. T2-inflammatory biomarkers may be useful in assessing airway inflammation activity and asthma-control assessment in children.
Maternal diabetes and overweight as risk factors for congenital heart defects in offspring - A nationwide register study from Finland
Authors: Turunen R , Pulakka A , Metsälä J , Vahlberg T , Ojala T , Gissler M , Kajantie E , Helle E
Published: February 2023

Importance

Congenital heart defects (CHDs) affect 1–2% of newborns and are associated with significant mortality and morbidity. Understanding risk factors underlying CHDs is essential for prevention.

Objective

To determine the association between maternal diabetes and overweight/obesity and CHDs among offspring.

Design

Nationwide population-based register study.

Setting

Finland

Participants

All children born between 2006–2016 (N=620 751), and their mothers.

Exposures

Maternal pre-pregnancy body mass index (BMI) categorized as underweight (<18.5 kg/m2), normal (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30 kg/m2). Maternal diabetes classified as no diabetes, type 1 (T1DM), type 2/other (T2DM), and gestational diabetes (GDM).

Main Outcomes and Measures

Odds ratio (OR) of isolated CHD in the child. In addition, nine anatomical CHD subgroups were studied.

Results

Of the 620 751 children born in Finland during the study period, 10 254 (1.65%) had an isolated CHD. T1DM was associated with an increased risk of having a child with any CHD (OR 3.71 (95% CI 3.16–4.35)), whereas maternal overweight (OR 0.98 (95% CI 0.98–1.04)) and obesity (OR 1.00 (95% CI 0.93–1.07)) were not. When analyzing anatomical subgroups, T1DM was associated with an increased risk in six subgroups. Maternal overweight was associated with complex defects (OR 2.24 (95% CI 1.01–4.94)), left ventricular outflow tract obstruction (OR 1.26, (95% CI 1.07–1.49), maternal obesity with complex defects (OR 3.22 (95% CI 1.31–7.92)), and right ventricular outflow tract obstruction (OR 1.26, (95% CI 1.01–1.55)). At the population level, maternal diabetes was responsible for 3.0% and maternal overweight and obesity for 0.7% of offspring’s CHD.

Conclusions and Relevance

This study indicated a less profound association between maternal overweight and obesity and CHD in the offspring than previously reported. The different risk profiles of T1DM and overweight/obesity may suggest distinct underlying teratogenic mechanisms.