bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of circLRWD1 weakens DDP resistance via reduction of SIRT5 expression through releasing miR-507 in non-small cell lung cancer
Authors: Deng Zhongbiao , Tu Qimin , Hu Guoliang , Xing Maohui
Published: August 2022

Cisplatin (DDP) is an antineoplastic agent for non-small cell lung cancer (NSCLC). Hsa_circ_0081664 (circLRWD1) is overexpressed in DDP-resistant NSCLC cells, but its function is unclear. Thus, this study is to investigate whether circLRWD1 participates in DDP resistance in NSCLC. Changes in circLRWD1 expression were determined by real-time quantitative PCR. Effects of circLRWD1 inhibition on DDP-resistant NSCLC cell viability, proliferation, migration, invasion, and apoptosis were analyzed. The sponge function of circLRWD1 was predicted by bioinformatics analysis and verified by dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. The function of circLRWD1 in DDP resistance was verified by xenograft models. CircLRWD1 was unconventionally overexpressed in DDP-resistant NSCLC samples and cells. Moreover, circLRWD1 silencing decreased IC50 value, restrained cell proliferation, reduced cell migration and invasion, and facilitated cell apoptosis in DDP-resistant NSCLC cells. Also, circLRWD1 knockdown elevated DDP-resistant NSCLC cell sensitivity to DDP in xenograft models. Furthermore, circLRWD1 regulated SIRT5 expression via adsorbing miR-507. SIRT5 overexpression weakened circLRWD1 silencing-mediated suppression of cell resistance to DDP in DDP-resistant NSCLC cells. In conclusion, circLRWD1 elevated SIRT5 expression via adsorbing miR-507, resulting in promoting NSCLC cell resistance to DDP, providing evidence to explain the significant role of circLRWD1 in DDP resistance in NSCLC.
Ado-trastuzumab emtansine in the treatment of lung adenocarcinoma with ERBB2 mutation: a case report and literature review
Authors: Wang Hao , He Yang , Zhao Weipeng , Tong Zhongsheng
Published: August 2022

The erb-b2 receptor tyrosine kinase 2 (ERBB2), also known as HER2, has long been recognized as an oncogenic driver in some breast and gastroesophageal cancers, and ERBB2-targeted therapies are standard for ERBB2-positive breast and gastric cancer. However, there are currently no standard therapies targeting the ERBB2 pathway in non-small cell lung cancer. Recently, somatic mutations in ERBB2 have been reported in 2–3% of patients with advanced lung adenocarcinoma, these mutations are trans-forming in lung cancer models and result in kinase activation, conferring some in-vitro sensitivity to trastuzumab. The ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate composed of trastuzumab joined via a stable linker to DM1. In this report, a 67-year-old male patient was diagnosed with advanced lung adenocarcinoma with multiple lymph node metastases, and multi-chemotherapy and immunotherapy were not effective. The results of genetic testing indicated a non-frameshift insertion mutation in exon 20 of the ERBB2 gene. The patients received T-DM1 at a dose of 3.6 mg/kg by intravenous infusion every 21 days until for 12 cycles. Partial response appeared in the tumor lesions after treatment for four cycles, and PET-computer tomography showed the tumor lesions were effectively controlled, and the efficacy evaluation was complete response after treatment for six cycles. Although the patient experienced second degree of thrombocytopenia during the treatment, the corresponding symptomatic treatment was taken, and the platelets could return to normal before the next cycle of T-DM1. Follow-up review showed the patient is in good health and the tumor has not recurred.
Defibrotide suppresses brain metastasis by activating the adenosine A2A receptors
Authors: Dong Ce , Zhu Lin , Yue Xiongfei , Sun Zheng , Wang Cong , Ye Zhanying , Pan Baogen
Published: August 2022

Brain metastasis is a devastating clinical condition globally as one of the most common central nervous system malignancies. The current study aimed to assess the effect of defibrotide, an Food and Drug Administration-approved drug, against brain metastasis and the underlying molecular mechanisms. Two tumor cell lines with high brain metastasis potential, PC-9 and 231-BR, were subjected to defibrotide treatment of increasing dosage. The metastasis capacity of the tumor cells was evaluated by cell invasion and migration assays. Western blotting was employed to determine the levels of tight junction proteins in the blood–brain barrier (BBB) including Occludin, Zo-1, and Claudin-5, as well as metastasis-related proteins including CXCR4, MMP-2, and MMP-9. The in-vitro observations were further verified in nude mice, by monitoring the growth of xenograft tumors, mouse survival and brain metastasis foci following defibrotide treatment. Defibrotide inhibited proliferation, migration, invasion, and promotes lactate dehydrogenase release of brain metastatic tumor cells, elevated the levels of BBB tight junction proteins and metastasis-related proteins. Such beneficial role of defibrotide was mediated by its inhibitory action on the SDF-1/CXCR4 signaling axis both in vitro and in vivo, as CXCR4 agonist SDF1α negated the anti-tumoral effect of defibrotide on mouse xenograft tumor growth, mouse survival and brain metastasis. Defibrotide inhibits brain metastasis through activating the adenosine A2A receptors, which in turn inhibits the SDF-1/CXCR4 signaling axis. Our study hereby proposes defibrotide as a new and promising candidate drug against brain metastasis of multiple organ origins.
Impressive response to dabrafenib and trametinib plus silybin in a heavily pretreated IDH wild-type glioblastoma patient with BRAFV600E-mutant and SOX2 amplification
Authors: Cerretti Giulia , Cecchin Diego , Denaro Luca , Caccese Mario , Padovan Marta , Zagonel Vittorina , Lombardi Giuseppe
Published: August 2022

Isocitrate dehydrogenase wild-type glioblastoma is the most frequent primary brain tumor in adult patients and its prognosis is still dismal with a median survival of about 1 year. BRAF

V600E
mutation, an important target for personalized therapy, has been identified in about 3% of these patients, but few data are available from prospective studies on the role of anti-BRAF drugs in adult glioblastoma patients. Moreover, SOX2 gene amplification and overexpression can represent an important mechanism of resistance to BRAF inhibitors by STAT3 gene activation. We present the case of a heavily pretreated 42-year-old man with BRAF

V600E
mutant and SOX2 amplification glioblastoma having a radiologic and metabolic [analyzed by a brain 18F-fluoro-ethyl-tyrosine([18F]FET) PET/MRI] complete response to the combination therapy with dabrafenib plus trametinib and silybin, a potent STAT3 inhibitor. The patient is currently undergoing treatment after a total of 24 months of continuation therapy with a good safety profile. In conclusion, we showed a promising activity of the personalized treatment of BRAF and MEK inhibitors in patient with BRAF

V600E
mutant glioblastoma; silybin can play an important role in decreasing drug resistance during BRAF inhibitor therapy, especially in patients with SOX2 amplification.
Novel Neurocognitive Profile in a Minority of Boys with 47,XXY (Klinefelter Syndrome)
Authors: Samango-Sprouse Carole A. , Hamzik Mary P. , Khaksari Kosar , Brooks Michaela R. , Sadeghin Teresa , Gropman Andrea L.
Published: August 2022

Introduction:

47,XXY, also known as Klinefelter syndrome, is the most commonly occurring sex chromosomal variation (1:660). The neurocognitive profile of boys with 47,XXY, in addition to verbal abilities, language skills, and general intelligence, has been explored in this study.

Methods:

Fifty-five participants with 47,XXY were segregated into groups according to their performance on the Wechsler Intelligence Scale for Children (WISC): (1) those with a higher performance intelligence quotient (PIQ) in comparison with their verbal IQ (VIQ) and (2) those with a higher VIQ compared with their PIQ. Two-tailed independent t tests were completed to analyze group differences.

Results:

Our study results demonstrate novel findings that one-third of subjects have higher verbal capabilities than perceptual skills. Those participants who showed the typical presentation of 47,XXY with increased PIQ in comparison with their VIQ excelled on perceptual and visual spatial subtests on the WISC and on nonverbal IQ on the Leiter International Performance Scale-III. In addition, it was found that expressive and receptive vocabulary skills were commensurate in both groups, which has not been reported previously.

Discussion:

To the best of our knowledge, this is the first study to identify an alternative profile of 47,XXY with increased verbal capabilities in comparison with perceptual skills. In addition, previous research has found that boys with 47,XXY often show increased receptive vocabulary skills in comparison with their expressive vocabulary skills early in life. Therefore, our findings of commensurate expressive and receptive vocabulary skills suggest that age may be an impactful factor in vocabulary development. Further research is necessary to determine individualized treatment options for these patients, focusing on the specific cognitive profile they present.
Potent Periorbital Fractionated CO2 Laser Resurfacing
Authors: Watson Alison H. , Van Brummen Alexandra , Somogyi Marie B. , Homer Natalie , Nakra Tanuj
Published: August 2022

BACKGROUND

The aged face results from a culmination of skin changes, gravitational descent, and volume loss. Surgical interventions in the periorbital region are beneficial for addressing these 3 factors. Despite this, studies describing CO2 laser safety settings are lacking.

OBJECTIVE

There is no present consensus on ideal periorbital CO2 laser; therefore, this study evaluates the safety of periorbital laser resurfacing as an adjunct to lower blepharoplasty using robust settings.

MATERIALS AND METHODS

A retrospective review was performed of all patients who underwent bilateral lower blepharoplasty with adjunctive periorbital (upper and lower eyelid) fractionated CO2 laser resurfacing from 2013 to 2018 performed by a single oculoplastic surgeon.

RESULTS

Fifty-nine patients were included. Six patients experienced side effects including postinflammatory hyperpigmentation, (3/59, 5.1%), prolonged superficial excoriations (1/59, 1.7%), prolonged hyperemia (1/59, 1.7%), and lower eyelid retraction requiring lower eyelid recession (1/59, 1.7%). None of the patients developed postoperative infection. All patient expressed satisfaction at their final postoperative visit.

CONCLUSION

CO2 laser resurfacing, even with robust settings, is a safe and effective adjunct to lower blepharoplasty.
OREX-1038: a potential new treatment for pain with low abuse liability and limited adverse effects
Authors: Gerak Lisa R. , Maguire David R. , Cami-Kobeci Gerta , Olson Keith M. , Traynor John R. , Husbands Stephen M. , France Charles P. , Acevedo Lisette , Belli Barbara , Flynn Peter
Published: August 2022

Drugs targeting mu opioid receptors are the mainstay of clinical practice for treating moderate-to-severe pain. While they can offer excellent analgesia, their use can be limited by adverse effects, including constipation, respiratory depression, tolerance, and abuse liability. Multifunctional ligands acting at mu opioid and nociceptin/orphanin FQ peptide receptors might provide antinociception with substantially improved adverse-effect profiles. This study explored one of these ligands, OREX-1038 (BU10038), in several assays in rodents and nonhuman primates. Binding and functional studies confirmed OREX-1038 to be a low-efficacy agonist at mu opioid and nociceptin/orphanin FQ peptide receptors and an antagonist at delta and kappa opioid receptors with selectivity for opioid receptors over other proteins. OREX-1038 had long-acting antinociceptive effects in postsurgical and complete Freund’s adjuvant (CFA)-induced thermal hyperalgesia assays in rats and a warm water tail-withdrawal assay in monkeys. OREX-1038 was active for at least 24 h in each antinociception assay, and its effects in monkeys did not diminish over 22 days of daily administration. This activity was coupled with limited effects on physiological signs (arterial pressure, heart rate, and body temperature) and no evidence of withdrawal after administration of naltrexone or discontinuation of treatment in monkeys receiving OREX-1038 daily. Over a range of doses, OREX-1038 was only transiently self-administered, which diminished rapidly to nonsignificant levels; overall, both OREX-1038 and buprenorphine maintained less responding than remifentanil. These results support the concept of dual mu and nociceptin/orphanin FQ peptide receptor partial agonists having improved pharmacological profiles compared with opioids currently used to treat pain.
Stabilizing Cardiac Ryanodine Receptor With Dantrolene Treatment Prevents Binge Alcohol–Enhanced Atrial Fibrillation in Rats
Authors: Greco Lisa V. , Migirov Allan , Ojamaa Kaie , Li Ying , Huang Yuan , Kobayashi Satoru , Udo-Bellner Lars , Stout Randy , Cohen Todd J. , Zhang Youhua
Published: August 2022

Binge drinking is a risk factor for cardiac arrhythmias, known as the holiday heart syndrome. Atrial fibrillation (AF) is the most frequently diagnosed arrhythmia in this condition. Recent reports indicated that cardiac ryanodine receptor (RyR2) dysfunction and Ca2+ leak contribute to alcohol-enhanced AF. In this study, we investigated whether stabilizing RyR2 with dantrolene treatment can prevent alcohol-enhanced AF in rats. A binge drinking rat model was established with alcohol (2g/kg, IP) delivered once every other day for 4 times. The study consisted of following 3 groups: control group (n = 9), binge alcohol group (n = 10), and binge alcohol + dantrolene (A+D) group (dantrolene, 10 mg/kg, IP before each alcohol injection, n = 9). Echocardiography, left ventricular hemodynamics, in vivo atrial electrophysiology and AF inducibility test, RyR2 phosphorylation level, and blood norepinephrine level were studied 24 hours after the last injection. Ca2+ leak in isolated atrial myocytes from control and binge alcohol rats was examined. Binge alcohol significantly increased AF inducibility (1/9 in control vs. 8/9 in binge alcohol group, P < 0.05) and AF duration. Dantrolene treatment significantly reduced both AF inducibility (2/9 in dantrolene group, P < 0.05) and AF duration. Binge alcohol significantly increased Ca2+ leak in isolated atrial myocytes, which was reduced by dantrolene treatment. Blood norepinephrine,7 RyR2 phosphorylation level, cardiac echocardiography, and left ventricular hemodynamics were not significantly affected 24 hours after binge drinking. In conclusion, stabilizing RyR2 with dantrolene treatment significantly attenuated binge drinking–enhanced AF, suggesting that therapeutic strategies stabilizing RyR2 could be a preventive measure to blunt binge drinking–enhanced AF arrhythmogenesis.
Direct and indirect health effects of the nuclear power plant disasters: a review for health care professionals
Authors: Okano Ichiro , Rosenberg Ashley , Dworkin Myles , Murthy Vijayashree , Jayaraman Sudha , Takabe Kazuaki
Published: August 2022

Background:

Nuclear power plants are deeply integrated into our society. They possess substantial risk for major disasters. Two of the worst-categorized nuclear power plant disasters were Chernobyl and Fukushima, emitting large amounts of radioactive materials and required mass evacuations in neighboring areas.

Methods:

This is a rapid review of the literature. We searched PUBMED and Medline for original studies of all large nuclear power plant disaster information documented in literature.

Results:

Eighty-three publications were identified in the review. The results are summarized in categories based on direct health effects such as immediate health effects, indirect health effects related to evacuation, cancer, behavioral effects and environmental effects like proliferation of wildlife and other infectious diseases.

Conclusion:

Nuclear power plant disasters have a great impact on human health including increased rates of cancer, behavioral and psychosocial problems, and evacuation related problems. These disasters can lead to major environmental impact, specifically on wildlife, resulting in unanticipated health consequences for local populations. In this review, we describe these consequences of nuclear power plant disasters as they apply to local health care workers.
Trends in pelvic pain symptoms over 2 years of follow-up among adolescents and young adults with and without endometriosis
Authors: Sasamoto Naoko , Shafrir Amy L. , Wallace Britani M. , Vitonis Allison F. , Fraer Cameron J. , Sadler Gallagher Jenny , DePari Mary , Ghiasi Marzieh , Laufer Marc R. , Sieberg Christine B. , DiVasta Amy D. , Schrepf Andrew , As-Sanie Sawsan , Terry Kathryn L. , Missmer Stacey A.
Published: August 2022

We described trends in pelvic pain characteristics over 2 years of follow-up among adolescents and adults with and without endometriosis participating in the longitudinal observational cohort of the Women's Health Study: From Adolescence to Adulthood, using data reported at baseline and at years 1 and 2 of follow-up. Participants completed a questionnaire at baseline (between November 2012 and May 2019) and annually thereafter that included validated measures of severity, frequency, and life interference of dysmenorrhea, acyclic pelvic pain, and dyspareunia. Our study population included 620 participants with surgically confirmed endometriosis (rASRM stage I/II = 95%) and 671 community-based and hospital-based controls, with median age = 19 and 24 years, respectively. The proportion reporting hormone use varied across the 3 years ranging from 88% to 92% for cases and 56% to 58% for controls. At baseline, endometriosis cases were more likely to report severe, frequent, and life-interfering dysmenorrhea, acyclic pelvic pain, and dyspareunia compared with controls. Among cases, frequency and severity of dysmenorrhea and dyspareunia were relatively static across 2 years. However, acyclic pelvic pain improved. Severe acyclic pain decreased from 69% at baseline to 46% at year 2. Daily pain decreased from 28% to 14%, and life interference from 68% to 38%. Trends among controls remained fairly stable across 2 years. Among endometriosis cases who completed the questionnaire at all 3 time points, 18% reported persistent, severe acyclic pelvic pain at all 3 time points. Over time, different trends were observed by pelvic pain type among endometriosis cases and controls, supporting the importance of assessing multidimensional features of pelvic pain.
Technological innovation and clinical application of direct percutaneous computed tomography–guided enterostomy versus other enterostomy techniques
Authors: Sun Ming-Yao , Zheng Tian , Chen Jian , Zhan Zhou-Wei , Wang Zeng-Lin , Chen Wei , Yang Chang-Shun , Zheng Xiao-Ling
Published: August 2022

Background:

To investigate the technological innovation, safety, operational advantages, and clinical application value of direct percutaneous computed tomography (CT)–guided enterostomy.

Methods:

This retrospective study included patients who underwent direct percutaneous CT-guided enterostomy (n = 52), percutaneous endoscopic gastrojejunostomy (PEG-J, n = 39), or laparoscopic jejunostomy (n = 68) at Fujian Provincial Hospital between October 2019 and July 2021. The study indices included stoma surgery success rate, operation time, complication rate, and postoperative pain score. We concurrently analyzed the technological innovation of direct percutaneous CT-guided enterostomy and the changes in body mass index (BMI), serum albumin, pre-albumin, and C-reactive protein (CRP) levels and patient-generated subjective global assessment (PG-SGA) scores after patients received 2 months of nutritional support.

Results:

Direct percutaneous CT-guided enterostomy had a high success rate (100%) and low postoperative complication rate (5.77%). Compared to laparoscopic jejunostomy, direct percutaneous CT-guided enterostomy had a shorter operation time (36.92 ± 10.60) min, lower postoperative pain score (4.06 ± 2.02), lower anesthesia risk, and lower operative cost. The anesthetic risk for direct percutaneous CT-guided enterostomy is lower than that for PEG-J and has wider applications. After 2 months of postoperative nutritional support, patients had increased BMI, serum albumin level, and serum pre-albumin level and decreased PG-SGA scores and CRP level with statistically significant differences compared to the preoperative state (p < 0.05).

Conclusion:

Direct percutaneous CT-guided enterostomy is an important method of establishing an enteral nutrition therapy pathway, especially when endoscopic jejunostomy is not possible. It has a high safety profile and few complications, has unique advantages, and deserves further promotion of its application in clinical practice.
The effect of tranexamic acid on myocardial injury in cardiac surgical patients: a systematic review and meta-analysis
Authors: Wang Xiao , Li Ling , He Lixian , Yao Yuntai
Published: August 2022

Tranexamic acid (TXA) is one of the most commonly used antifibrinolytic agents for surgical patients. However, the effect of TXA on myocardial injury remains controversial. We systemically reviewed literature regarding the effectiveness of TXA on myocardial injury in patients who have undergone a cardiac surgery. We included all randomized controlled trials (RCTs) comparing TXA and control (saline) in cardiac surgical patients. Relevant studies were identified by a comprehensive electronic literature search from database inception to 15 August 2021. A standardized data extraction form was used to collect methodological and outcome variables from each eligible study. We conducted a meta-analysis to estimate the pooled effect size of TXA administration on myocardial injury. In total, eight RCTs were identified, with 292 patients in the TXA group, and 241 patients in saline or control group. The meta-analysis demonstrated that patients in the TXA group had lower levels of CK-MB and cTnI within 24 h postoperatively (CK-MB: P = 0.005; cTnI: P = 0.01), compared with the saline group. No significant difference was found with respect to AST level (P = 0.71) between TXA and saline groups within 24 h postoperatively. TXA administration was found to be associated with less myocardial injury among patients who have undergone cardiac surgery. High-quality randomized controlled trials are warranted to further examine the cardioprotective effects of TXA.
Interleukin-10 levels and the risk of thromboembolism according to COMPASS-Cancer associated thrombosis score in breast cancer patients prior to undergoing doxorubicin-based chemotherapy
Authors: Pestana Rodrigo M.C. , Alves Michelle T. , de Oliveira Angélica N. , Oliveira Heloísa H.M. , Soares Cintia E. , Sabino Adriano de P. , Silva Luciana M. , Simões Ricardo , Gomes Karina B.
Published: August 2022

Venous thromboembolism (VTE) is an important cause of morbidity/mortality in cancer patients, and COMPASS-CAT score must be used to VTE-risk prediction. There is a relationship between cytokines and thrombus formation and/or resolution. This study aimed to investigate the VTE risk and cytokines level in breast cancer patients prior to chemotherapy with doxorubicin (DOXO). Eighty women with breast cancer and indication for DOXO treatment were selected. TNF, IL-1β, IL-6, and IL-10 were measured after the diagnosis and immediately before DOXO treatment. All 80 patients presented a high risk for VTE when evaluated by COMPASS-CAT model (score ≥7). A positive correlation was observed between IL-10 plasma levels and VTE risk score. Our data showed that higher IL-10 levels before chemotherapy are associated to increased risk of VTE in breast cancer patients. This finding suggests that IL-10 levels and the combination with COMPASS-CAT score could be good markers to predict increased risk of VTE in these patients.
Reversal of life-threatening bleeding with protamine sulfate in a patient with plasma cell leukemia
Authors: VanDommelen Kyle , Omer Zulfa , Hambley Bryan C. , Stefaniuk Catherine M.
Published: August 2022

Plasma cell disorders, such as multiple myeloma, can cause numerous derangements of hemostasis. In this case report, we present a life-threatening coagulopathy in a patient with progressing multiple myeloma in which the antibody-producing heparin-like activity is a free light chain. The patient's bleeding was successfully treated using protamine sulfate, which then allowed treatment of her plasma cell leukemia. In the literature, other authors have reported similar patients who have responded to protamine sulphate either in vitro or in vivo, providing further evidence for the role of protamine sulfate in the reversal of coagulopathy and resolution of bleeding diathesis. Standard treatments of transfusion with fresh frozen plasma and cryoprecipitate are likely to be ineffective in life-threatening bleeding related to this mechanism (heparin-like effect), and it is essential that treating physicians are aware of this potential mechanism of bleeding in their patients.
Lupus anticoagulant activity and thrombosis post COVID-19 vaccination
Authors: Al-Ahmad Mona , Al Rasheed Mona , Altourah Lulwa , Rodriguez-Bouza Tito , Shalaby Neveen
Published: August 2022

Some reports have discussed the development of a new entity called vaccine-induced immune thrombotic thrombocytopenia after COVID-19 vaccination. In this case series, we are describing four patients who have developed lupus anticoagulant-associated venous thromboembolism after Pfizer mRNA COVID-19 vaccination. All were COVID-19 negative on admission. Three had developed thrombosis after the first dose and one after the second dose of vaccination. All of them had venous thrombosis. Three patients developed thrombosis 2 weeks after vaccination and the fourth patient had developed thrombosis after 3 weeks of vaccination. None of the patients had thrombocytopenia on or during admission as seen in the case of vaccine-induced immune thrombotic thrombocytopenia. All patients had positive lupus anticoagulant and negative anticardiolipin antibodies and antibeta2 glycoprotein I. All of them were stable on discharge and were treated with low molecular weight heparin followed by warfarin. We suggest the presence of a possible link between the development of antiphospholipid antibodies and COVID-19 vaccine that requires further assessment.
Congenital factor V deficiency in Taiwan: identification of a novel variant p.Tyr1813∗ and two variants specific to East Asians
Authors: Lin Hsuan-Yu , Lin Ching-Yeh , Kuo Su-Feng , Lin Jen-Shiou , Lin Po-Te , Huang Ying-Chih , Hsieh Han-Ni , Shen Ming-Ching
Published: August 2022

Congenital coagulation factor V deficiency (FVD) is a rare, autosomal recessive bleeding disorder. We characterized the clinical presentations, laboratory features, and genetic alterations of Taiwanese patients with FVD. From 1983 to 2010, five women, one man, and one boy diagnosed with FVD were enrolled in this study. The factor V coagulant activity was determined using a one-stage prothrombin time-based test. The factor V antigen level was measured in an ELISA. Sanger sequencing was performed for genetic analyses of F5, the gene responsible for the disease. One novel and de novo F5 genetic variant, p.Tyr1813∗, was identified. Based on the presence of a premature termination codon with a resultant truncated factor V-protein lacking an intact light chain fragment, the variant is pathogenic. In addition, we identified seven variants previously found to cause FVD. Among them, p.Gly420Cys and p.Asp96His were repeatedly detected in five and four patients, respectively. Both variants are found to be specific to the East Asian populations. Various FVD-associated bleeding manifestations were observed, predominantly mucocutaneous bleeding and hypermenorrhea. All patients exhibited very low factor V coagulant activity (<1–2.5 IU/dl, reference range: 60–133 IU/dl). The factor V antigen level was less than 2% in six patients (reference range: 75–157%). The novel F5 genetic variant p.Tyr1813∗ and two distinct, East Asians-specific, recurrent variants p.Gly420Cys and p.Asp96His were identified among seven index patients with FVD in Taiwan. Our clinical and laboratory findings support the reported features of FVD.
Early cardiac rehabilitation after heart transplantation in a patient with limb-girdle muscular dystrophy: A case report
Authors: Kim Youngmo , Park Min Kyung , Shin Myung-Jun , Shin Yong Beom , Lee Hye Won , Yun Ra Yu , Lee Byeong-Ju
Published: August 2022

Rationale:

Cardiac rehabilitation (CR) after heart transplantation (HT) decreases the mortality rate and increases exercise capacity of patients. Dilated cardiomyopathy develops in most patients with muscular dystrophy (MD), leading to advanced heart failure, necessitating the use of left ventricular assist devices or HT. As the clinical outcomes of left ventricular assist devices and HT in patients with myopathy differ from those in patients without myopathy, CR adapted to patients with MD should be considered.

Patient concerns:

A 39-year-old man with limb-girdle muscular dystrophy developed dilated cardiomyopathy and underwent HT.

Diagnosis:

The patient was diagnosed as having limb-girdle muscular dystrophy in 1997.

Intervention:

Early CR was performed based on the patient’s physical condition and ability.

Outcomes:

With chest physiology, aerobic, and resistance exercises, the patient was able to walk using a walker 28 days after HT. This is important because his lower-extremity strength and walking ability were, to some extent, maintained after surgery.

Lessons:

Since an increasing number of patients with MD are undergoing HT, specific CR programs for these patients should be discussed.
The association between the neutrophil to lymphocyte ratio and in-hospital mortality among sepsis patients: A prospective study
Authors: Chebl Ralph Bou , Assaf Mohamad , Kattouf Nadim , Haidar Saadeddine , Khamis Mohamed , Abdeldaem Karim , Makki Maha , Tamim Hani , Dagher Gilbert Abou
Published: August 2022

The Neutrophil to lymphocyte ratio (NLR) was shown to be associated with disease severity, poor prognosis and increased mortality in sepsis. However, the association between NLR and sepsis prognosis remains controversial.

Our study aims to prospectively examine the prognostic ability of NLR in predicting in-hospital mortality among sepsis patients and determine the optimal cutoff of NLR that can most accurately predict in-hospital mortality in sepsis patients. This study was a prospective cohort study that included adult sepsis patients that presented to the emergency department of a tertiary care center between September 2018 and February 2021.

Receiver operating characteristic curve was used to determine the optimal cutoff of the neutrophil to lymphocyte ratio that predicts in-hospital mortality. Patients were divided into 2 groups: above and below the optimal cutoff. Stepwise logistic regression was performed to assess the magnitude of the association between NLR and in-hospital mortality.

A total of 865 patients were included in the study. The optimal cutoff for the neutrophil to lymphocyte ratio that predicts in-hospital mortality was found to be 14.20 with a sensitivity of 44.8% and a specificity of 65.3% (with PPV = 0.27 and NPV = 0.80). The area under the curve for the ratio was 0.552 with a 95% confidence intervals = [0.504–0.599] with a P value = .03. Patients that have a NLR above the cutoff were less likely to survive with time compared to patients below the cutoff based on the Kaplan–Meier curves. In the stepwise logistic regression, the optimal neutrophil to lymphocyte ratio cutoff was not associated with in-hospital mortality (odds ratios = 1.451, 95% confidence intervals = [0.927–2.270], P = .103).

In conclusion the optimal cutoff of the NLR that predicts in-hospital mortality among sepsis patients was 14.20. There was no association between the NLR and in-hospital mortality in sepsis patients after adjusting for confounders. Further studies with a larger sample size should be done to determine the optimal NLR cutoff and its prognostic role in septic patients (in-hospital mortality and other clinically significant outcomes).
Correlation between medical student empathy and a Korean nationwide comprehensive clinical assessment score at a medical school in Korea
Authors: Jung Min Kyu , Yeo Sanghee , Lee Won Kee
Published: August 2022

Empathy is the ability to understand and communicate a patient’s situation, perspective, and feelings. When demonstrated by healthcare professionals, this can improve patient adherence, satisfaction, and treatment outcomes. Empathic students have stronger affective skills and can acquire, develop, reinforce, and display strong affective behaviors, abilities, and attitudes.

We measured student empathy using the Student Version of the Jefferson Scale of Empathy (JSE-S) and assessed 3-year sequential clinical comprehensive assessment scores conducted by the Korean Medical Education Assessment Corporation to determine the relationship between JSE-S and clinical comprehensive assessment scores.

The study population comprised of 80 males (74%) and 28 females (26%), among which 38 (35%) and 62 (57%) students wanted to become private physicians and attending faculty, respectively. Regarding future majors, 58 students (54%) considered medical fields, whereas 40 students (37%) considered surgical fields. No significant differences in Korean JSE-S were observed according to medical student gender, career aspirations, or future major fields.

The modified Korean version of the JSE-S has 18 items. Item-total score correlations and Cronbach α evaluated the internal consistency reliability of the scale. The reliability of the Korean JSE-S was 0.910 by Cronbach α coefficient.

Female students had better scores than males. Students who wanted to be an attending faculty had better scores than others who wanted to be private physicians; however, these findings were not statistically significant. Significantly higher scores were seen among students aspired to work in the medical field (65.6 ± 8.8) versus in the surgical field (60.4 ± 8.2) in their 5th year (P < .01).

We were unable to show the positive correlations between the empathy scale and comprehensive assessment results. Among female medical students, comprehensive assessment results were inversely correlated with empathy toward the patient, but this was not statistically significant.

The modified Korean JSE-S has acceptable reliability. Every student had a better comprehensive assessment after studying the medical curriculum between the 4th and 6th years. The current nationwide assessment tool does not measure student empathy.
Regional 18F-fluoromisonidazole PET images generated from multiple advanced MR images using neural networks in glioblastoma
Authors: Qin Jianhua , Tang Yu , Wang Bao
Published: August 2022

Generated 18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET) images for glioblastoma are highly sought after because 18F-FMISO can be radioactive, and the imaging procedure is not easy. This study aimed to explore the feasibility of using advanced magnetic resonance (MR) images to generate regional 18F-FMISO PET images and its predictive value for survival.

Twelve kinds of advanced MR images of 28 patients from The Cancer Imaging Archive were processed. Voxel-by-voxel correlation analysis between 18F-FMISO images and advanced MR images was performed to select the MR images for generating regional 18F-FMISO images. Neural network algorithms provided by the MATLAB toolbox were used to generate regional 18F-FMISO images. The mean square error (MSE) was used to evaluate the regression effect. The prognostic value of generated 18F-FMISO images was evaluated by the Mantel-Cox test.

A total of 299 831 voxels were extracted from the segmented regions of all patients. Eleven kinds of advanced MR images were selected to generate 18F-FMISO images. The best neural network algorithm was Bayesian regularization. The MSEs of the training, validation, and testing groups were 2.92E-2, 2.9E-2, and 2.92E-2, respectively. Both the maximum Tissue/Blood ratio (P = .017) and hypoxic volume (P = .023) of the generated images were predictive factors of overall survival, but only hypoxic volume (P = .029) was a predictive factor of progression-free survival.

Multiple advanced MR images are feasible to generate qualified regional 18F-FMISO PET images using neural networks. The generated images also have predictive value in the prognostic evaluation of glioblastoma.
The prognosis of refractory hypotension and severe intraventricular hemorrhage in very low birth weight infants
Authors: Hwang-Bo Seok , Seo Yu-Mi , Oh Moon-Yeon , Im Soo-Ah , Youn Young-Ah
Published: August 2022

Background:

The increased survival rate among very low birth weight infants has resulted in a higher risk for developing neuro-complications such as intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and adverse neurodevelopmental outcomes.

Purpose:

We examined refractory hypotension experienced within a week of life in association with severe IVH (grades 3–4) among very low birth weight infants (VLBWIs).

Method:

Between Jan 2014 and Dec 2017, the clinical data of 191 VLBWIs were retrospectively chart reviewed. Of a total of 191 VLBWIs, 71.2% (136/191) had IVH, and 28.7% (55/191) had severe IVH.

Results:

The VLBWI with severe IVH group (grade 3–4) presented with a significantly lower gestational age along with higher use of postnatal hydrocortisone for refractory hypotension within a week of life. Resuscitation at delivery, pulmonary hemorrhage, neonatal seizure, and PVL were significantly more frequent in the severe IVH group (P < .05). Higher mortality occurred in the VLBWI with severe IVH group (P < .001). The multivariable logistic regression analysis consistently showed that refractory hypotension within a week of life and neonatal seizures were significantly associated with severe IVH. Those in the severe IVH and refractory hypotension groups had significantly lower composite cognitive, language, motor scores in Bayley Scales of Infant and Toddler Development III scores at corrected 18–24 months.

Conclusion:

Refractory hypotension within a week of life and seizures were consistently associated with severe IVH and developmental delay at corrected 18–24 months. VLBWI who experienced refractory hypotension within a week of life may indicate a more vulnerable clinical setting with a higher risk for developmental delay.
Intravenous plus intraventricular tigecycline-amikacin therapy for the treatment of carbapenem-resistant Klebsiella pneumoniae ventriculitis: A case report
Authors: Li Jiyao , Liu Yiguo , Wu Guangtao , Wang Hongyan , Xu Xiaoyan
Published: August 2022

Rationale:

Central nervous system infections (CNSIs) are one of the most serious complications after neurosurgery, especially carbapenem-resistant bacterial meningitis. Owing to the poor blood-brain barrier permeability of most antibiotics, the treatment of CNSIs by intraventricular (IVT) administration is becoming a hot topic in clinical research. Currently, the treatment of CNSIs caused by carbapenem-resistant Klebsiella pneumoniae is mainly based on intraventricular injection of an antibiotic combined with one or more other systemic intravenous (IV) antibiotics, whereas there are few case reports of intraventricular injection of 2 antibiotics.

Patient concerns:

A 57-year-old man with an open craniocerebral injury presented with dyspnea, high fever, and seizures associated with surgery.

Diagnosis:

Intracranial infection caused by carbapenem-resistant K. pneumoniae was diagnosed.

Interventions:

On the advice of a clinical pharmacist, the patient was given tigecycline (100 mg IV + 3 mg IVT q12h) combined with amikacin (0.8 g IV + 30 mg IVT qd) antiinfective therapy. Ultimately, the pathogens in the cerebrospinal fluid were eradicated after 7 days, and the CNSIs were completely cured after 14 days.

Outcomes:

The patient recovered and was discharged from the hospital without adverse reactions.

Lessons:

A series of in vitro and in vivo synergy tests of carbapenem-resistant K. pneumoniae showed that tigecycline combined with aminoglycosides had good synergistic effects and effectively suppressed bacterial resistance selection. Intravenous plus intraventricular tigecycline-amikacin seems to be a safe and effective treatment option for carbapenem-resistant K. pneumoniae CNSIs.
Cardioprotective effect of Chinese herbal medicine for anthracycline-induced cardiotoxicity in cancer patients: A meta-analysis of prospective studies
Authors: Hao Wei , Shi You-Yang , Qin Yue-Nong , Sun Chen-Ping , Chen Li-Ying , Wu Chun-Yu , Bao Yi-Jia , Liu Sheng
Published: August 2022

Background:

To assess the benefits and harmful effects of Chinese herbal medicine (CHM) formulations in preventing anthracyclines (ANT)-induced cardiotoxicity.

Method:

The Cochrane Library, Pubmed and EMBASE databases were electronically searched for relevant randomized controlled trials (RCTs) published till December 2021 in English or Chinese-language, in addition to manual searches through the reference lists of the selected papers, and the Chinese Conference Papers Database. Data was extracted by 2 investigators independently.

Result:

Seventeen RCTs reporting 11 different CHMs were included in this meta-analysis. The use of CHM reduced the occurrence of clinical heart failure (RR 0.48, 95% CI 0.39 to 0.60, P < .01) compared to the control group. Data on subclinical heart failure in terms of LVEF values showed that CHM reduced the occurrence of subclinical heart failure (RR 0.47, 95% CI 0.35 to 0.62, P < .01) as well.

Conclusion:

CHM is an effective and safe cardioprotective intervention that can potentially prevent ANT-induced cardiotoxicity. However, due to the insufficient quality of the included trials, our results should be interpreted with cautious.
COVID-19 and Guillain-Barré syndrome: A single-center prospective case series with a 1-year follow-up
Authors: Ahmad Lara , Businaro Pietro , Regalbuto Simone , Gastaldi Matteo , Zardini Elisabetta , Panzeri Marta , Vegezzi Elisa , Fiamingo Giuseppe , Colombo Elena , Ravaglia Sabrina
Published: August 2022

Single reports of Guillain-Barré syndrome (GBS) have been reported worldwide during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. While case reports are likely to be biased toward uncommon clinical presentations, systematic assessment of prospective series can highlight the true clinical features and spectrum. In this prospective, observational study, we included all consecutive patients who developed GBS. In patients with SARS-CoV-2 infection as antecedent, the time-gap between the infection and GBS onset had to be ≤30 days. The referral was a neurological University Research Hospital, in the Italian Region more severely involved by the pandemic, and hospitalizing both COVID+ and non-COVID neurological diseases. Clinical, laboratory, cerebrospinal fluid, and electromyographic features of GBS diagnosed between March 2020 and March 2021 were compared to a retrospective series of GBS diagnosed between February 2019 and February 2020 (control population). Nasopharyngeal swab was still positive at GBS onset in 50% of patients. Mild-to-moderate COVID-related pneumonia, as assessed by X-ray (6 patients) or X-ray plus computerized tomography (2 patients) co-occurred in 6 of 10 patients. GBS diagnosed during the pandemic period, including 10 COVID-GBS and 10 non–COVID-GBS, had higher disability on admission (P = .032) compared to the GBS diagnosed between February 2019 and 2020, possibly related to later hospital referral in the pandemic context. Compared to non–COVID-GBS (n = 10) prospectively diagnosed in the same period (March 2020–2021), post–COVID-GBS (n = 10) had a higher disability score on admission (P = .028), lower sum Medical Research Council score (P = .022) and lymphopenia (P = .025), while there were no differences in GBS subtype/variant, severity of peripheral involvement, prognosis and response to treatment. Cerebrospinal fluid search for SARS-CoV-2 RNA and antiganglioside antibodies were negative in all COVID+ patients. Temporal clustering of cases, coinciding with the waves of the pandemic, and concomitant reduction of the incidence of COVID-negative GBSs may indicate a role for SARS-CoV-2 infection in the development of GBS, although the association may simply be related to a bystander effect of systemic inflammation; lack of prevalence of specific GBS subtypes in post–COVID-GBS also support this view. GBS features and prognosis are not substantially different compared to non–COVID-GBS.
An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis
Authors: Huang Taobi , Xu Jinlan , Wang Maoying , Pu Ke , Li Longquan , Zhang Huiyun , Liang Yuan , Sun Weiming , Wang Yuping
Published: August 2022

Background:

Fecal microbiota transplantation (FMT) as a promising therapy for ulcerative colitis (UC) remains controversial. We conducted a systematic review and meta-analysis to assess the efficiency and safety of FMT as a treatment for UC.

Methods:

The target studies were identified by searching PubMed, EMBASE, the Cochrane Library, Web of Science, and ClinicalTrials and by manual supplementary retrieval. We conducted a general review and quantitative synthesis of included studies. We used the RevMan and Stata programs in the meta-analysis. The outcomes were total remission, clinical remission, steroid-free remission, and serious adverse events. We also performed subgroup analyses based on different populations.

Results:

A total of 34 articles were included in the general review. Only 16 articles, including 4 randomized controlled trials, 2 controlled clinical trials, and 10 cohort studies, were selected for the meta-analysis. We found that donor FMT might be more effective than placebo for attaining total remission (risk ratio [RR]: 2.77, 95% confidence interval [CI]: 1.54–4.98; P = .0007), clinical remission (RR: 0.33, 95% CI: 0.24–0.41; P < .05), and steroid-free remission (RR: 3.63, 95% CI: 1.57–8.42; P = .003), but found no statistically significant difference in the incidence of serious adverse events (RR: 0.88, 95% CI: 0.34–2.31, P = .8). The subgroup analyses revealed significant differences between the pooled clinical remission rates for different regions, degrees of severity of the disease, and patients with steroid- or nonsteroid-dependent UC.

Conclusions:

FMT can achieve clinical remission and clinical response in patients with UC.
Successful limb salvage in progressive proximal tibia osteosarcoma following denosumab chemotherapy: A case report
Authors: Chen Qian , Wu Junjie , Zheng Kai , Xu Ming , Hou Ziwei , Yu Xiuchun
Published: August 2022

Rationale:

Osteosarcoma (OS) is a primary malignant bone tumor that originates in the mesenchymal tissue. It is the most common type of pleomorphic tumor occurring in children and adolescents. Currently, there is no established systematic treatment for OS that progresses during standard preoperative chemotherapy.

Patient concerns and diagnoses:

We describe a 14-year-old male patient with a 4-month history of pain in the upper right leg. Based on the results of percutaneous biopsy, a diagnosis of OS was made. After admission, the patient was treated with first-line chemotherapy agents. After a single course of treatment, the tumor progressed locally and no limb salvage was feasible.

Interventions and outcomes:

Intervention with denosumab combined with chemotherapy led to a significant reduction in tumor volume and ossification of soft tissue, which successfully resulted in limb salvage rather than amputation. The patient showed no evidence of recurrent or distant metastasis at 6-month follow-up.

Lessons:

Treatment with receptor activator of nuclear factor-ĸB ligand inhibitor denosumab combined with standard chemotherapy is effective for advanced OS progressing after chemotherapy. We recommend denosumab therapy for successful limb salvage in patients with high-grade OS associated with osteolytic bone destruction and refractory to preoperative neoadjuvant chemotherapy.