Bilateral acute depigmentation of the iris (BADI) and bilateral acute iris transillumination (BAIT): A case series from a center in Brazil

ABSTRACT Bilateral acute depigmentation of the iris and bilateral acute iris transillumination (BAIT) are similar clinical entities. The former causes acute-onset depigmentation of the iris stroma without transillumination, whereas the latter causes depigmentation of the iris pigment epithelium with transillumination. The etiopathogenesis of these conditions is not yet fully understood, but the proposed causes include the use of systemic antibiotics (especially moxifloxacin) and viral triggers. We present a case series of five female patients with a mean age of 41 (32-45) years, all of whom suffered acute onset of bilateral pain and redness of the eyes after moxifloxacin use (oral or topical). It is important for ophthalmologists to be aware of the two forms of iris depigmentation since this case series suggests that SARS-CoV-2 or its empirical treatment with moxifloxacin may trigger iris depigmentation. If this is the case, clinicians will likely see increased incidences of bilateral acute depigmentation of the iris and bilateral acute iris transillumination during and after the COVID-19 pandemic.

Cerebellar ataxia after a single day of metronidazole use: Case report

Cerebellar ataxic syndromes, although uncommon, have been reported previously in patients taking metronidazole. However, almost all cases describe instances where patients were taking prolonged or high doses of the drug. We report a 65-year-old man who consumed 400 mg of metronidazole 3 times over 1 day and presented with slurring of speech, imbalance while walking and diplopia. The symptoms developed the day after consumption of metronidazole. Examination showed slurring of speech, gaze-evoked nystagmus, and dysmetria in all limbs. MRI brain revealed symmetric hyperintense lesions in the dentate nucleus and pons on T2-weighted imaging and FLAIR, which have a well-established association with metronidazole-induced central nervous system (CNS) toxicity. On discontinuation of the drug, symptoms improved, and complete recovery was noted at follow-up 2 weeks later. This case indicates that CNS side effects of metronidazole may not necessarily occur only at high doses or after prolonged courses of metronidazole, but may occur as an idiosyncratic reaction to the drug. Reasons for variable susceptibility require further investigation.

Clinical research progress of palbociclib in treatment of breast cancer / 中国临床药理学与治疗学

Palbocicril, the first cyclin-dependent kinases 4 and 6 inhibitors, is a crucial milestone in the development history of antineoplastic drugs. It combined with aromatase inhibitor or fulvestrant as first-line, second-line or post-line therapy has good efficacy and safety for hormone receptor-positive, human epidermal growth factor receptor-2 negative locally advanced or metastatic breast cancer, which has a good application prospect. This article summarizes the clinical trials and safety studies related to palbociclib.

Detection of BCR-ABL Fusion Gene in Chronic Myeloid Leukemia by Novel Digital PCR / 中国实验血液学杂志

OBJECTIVE@#To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABLp190/210/230.@*METHODS@#A new dPCR system for detecting BCR-ABLp190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared.@*RESULTS@#Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal.@*CONCLUSIONS@#This new dPCR detection system can be applied to the detection of BCR-ABLp190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.

Advances in clinical and safety studies of phosphodiesterase 4 inhibitors / 药学学报

Phosphodiesterase 4 (PDE4) is an important member of the phosphodiesterase enzyme family that specifically catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP), activates the downstream phosphorylation cascade pathway by altering cAMP concentration, and is strongly associated with multiple diseases. Inhibition of PDE4 is clinically investigated as a therapeutic strategy in a broad range of disease areas, including respiratory system diseases, autoimmune disorders, central nervous system diseases, and dermatological conditions. However, the incidence of adverse reactions such as nausea and vomiting is relatively high in the marketed PDE4 inhibitors, which has stalled their clinical development. In this review, we provide an overview of the clinical progression and safety issues of the marketed PDE4 inhibitors. We also review the main causes underlying PDE4-mediated adverse effects by combining the structural analysis of the PDE4 protein, the mechanism of action of PDE4 inhibitors, and the related side effect mechanism research, aiming to provide a reference for the development of safe and effective PDE4 inhibitors.

Survey data of COVID-19 vaccine side effects among Qassim University members

Background:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially reported as a culprit for many unexplained cases of pneumonia in Wuhan, China. Since then, COVID-19 vaccine is highly recommended as a protective measure of this pandemic. This study aimed to measure the safety profile of theCOVID-19 vaccine among Qassim University members.Methods:This is a cross-sectional observational study conducted among Qassim University members, Saudi Arabia. A pre-specified questionnaire was distributed among prospective members of the campus using an online survey. Participants who were vaccinated by either one or two doses were the subjects of this study. Consent was sought from the participants or next of kin and the data collection were lasted for over three months.Results:The 604 respondents were able to recruit (51.7% males versus 48.3% females). 55.6% of respondents were in the younger age group (age ?25 years). The most commonly received vaccine was Pfizer (67.3%) while the most common side effect was local pain at the site of injection (89.4%) and tiredness (76.7%). Females were significantly more being associated with having COVID-19 vaccine side effects, while complained about fever was significantly higher in the AstraZeneca vaccine (p<0.001).Conclusions:Our findings were consistent with literatures, our study finds local pain at the site of injection, tiredness, muscle pain, headache and fever as the most common side effects of the COVID-19 vaccine. The side effects of the COVID-19 vaccine had a greater impact on female respondents than their male counterparts.

Impact of reminder on medication adherence: a structural equation model, based on study in Sikkim, India

The problem of medication non-adherence has persisted over decades. The rate of adherence decreases with time and improvement in health condition. When patients cannot follow their prescribed medication regime, it leads to deterioration of their health condition and increases their financial costs. This research aims to find the effect of reminder on medication adherence behaviour of patients when "Acceptance of Side Effect", "Quality of Life" and "Medication Beliefs" act as mediators. The sample size of the research was 505. Sampling units comprised patients suffering from different diseases in Central Referral Hospital, Sikkim, India. By developing a Structural Equation Model, the effect of reminder on the mediators and adherence was analysed. The results show a significant positive association between reminder and the three mediators. Reminder has a significant positive effect on adherence (ß=0.637, e=0.055, p=0.001). The effect is higher in the presence of mediators (ß=0.7, e=0.037, p=0.001).

Advances in the application of preventive extended-field radiotherapy to advanced cervical cancer / 中华放射肿瘤学杂志

Cervical cancer is a common malignant tumor in gynecology, and its morbidity and mortality rates rank the fourth among female malignant tumors. Lymph node metastasis is the most important pattern of metastasis and a critical independent prognostic factor for cervical cancer. Considering the high missed diagnosis rate of para-aortic lymph node metastasis, and the high treatment failure rate caused by para-aortic lymph node metastasis after cervical cancer treatment, a small number of clinicians have applied preventive extended-field radiotherapy in the treatment of patients with Ⅲ B and Ⅲ c1 cervical cancer in recent years. This article reviews the prognosis and side effects of preventive extended-field radiotherapy in patients with stage Ⅲ B and Ⅲ c1 cervical cancer.

Ziprasidone-induced stuttering： a case report / 四川精神卫生

This paper reported a case of a 25-year-old male schizophrenic patient， who obtained remission from psychotic symptoms during the treatment of olanzapine and trihexylphenidyl， was given ziprasidone treatment additionally due to the occurrence of auditory hallucination， and developed stuttering 4 days later. The stuttering disappeared 2 days following the discontinuation of therapy， and reappeared after reinstitution of ziprasidone therapy， but disappeared again after discontinuation. The dose of olanzapine was increased to 20 mg/d to ensure the stability of psychotic remission. At a follow-up visit 4 months later， the patient’s mental condition was stable and stuttering did not recur， indicating that the stuttering was induced by ziprasidone. This case suggests that the possibility of stuttering as an adverse reaction should be considered in the clinical application of ziprasidone.

Multiple cutaneous telangiectasias after the use of trastuzumab: a case report

We aim to report a particular case of cutaneous telangiectasias on the arms after immunotherapy with trastuzumab plus paclitaxel to treat breast cancer. New oncology therapies reflect a major advance in cancer treatment. They greatly increase survival; however, they still cause certain adverse cutaneous events that should be taken into account for their proper management.

Safety of Rituximab combined with intensive chemotherapy in the treatment of childhood aggressive mature B-cell lymphoma/leukemia / 中华实用儿科临床杂志

Objective:To investigate the safety of Rituximab combined with intensive chemotherapy in the treatment of aggressive mature B-cell lymphoma/leukemia in children.Methods:The clinical data of 77 patients with primary pediatric aggressive mature B-cell lymphoma/leukemia who were treated according to the Chinese Children Cancer Group(CCCG)-mature B-cell lymphoma(BNHL)-2015 protocol at Shanghai Children′s Medical Center, School of Medicine, Shanghai Jiaotong University School from November 1, 2014 to July 31, 2018 were collected.A comparison was drawn on the adverse reactions and recovery of immune function indexes between patients in the Rituximab combined with intensive chemotherapy group (R4 group) and the chemotherapy alone group (R3 group).Results:Rituximab combined with AA was associated with a significantly lower platelet count [79.5%(35/44 cases) vs.54.5%(24/44 cases), χ2=6.223, P=0.011] and a higher incidence of infection [70.5%(31/44 cases) vs.36.4%(16/44 cases), χ2=10.275, P=0.001] compared with AA alone; Rituximab combined BB was associated with a higher incidence of mucositis and infection compared with BB alone [40.8%(20/49 cases) vs.29.3%(22/75 cases) and 85.7%(42/49 cases) vs. 72.0%(54/75 cases), respectively], but the differences were not statistically significant.A greater proportion of patients in the R4 group had a decrease in peripheral blood CD 19 positive cells (no statistically significant difference, P>0.05) and a greater proportion had a decrease in serum IgG ( P<0.05) compared to the R3 group, but there was no significant difference in treatment-related mortality between both groups.For patients in the R4 group, the average recovery time of IgG and IgM level was 13.1 months, and the longest recovery time was 31 months after the end of treatment. Conclusions:Rituximab combined with intensive chemotherapy is generally safe in the treatment of aggressive mature B-cell lymphoma/leukemia in children.However, it is often accompanied with prolonged immunoglo-bulin deficiency and the potential risk of secondary infection.Therefore, the strict control over the indications for its application is required, and the gamma globulin replacement therapy deserves to be investigated in the future.

A case report of colchicine-induced myopathy in a patient with chronic kidney disease / 北京大学学报(医学版)

Colchicine plays an important role in the treatment of gout and some other diseases. Besides gastrointestinal symptoms, myopathy has been reported as a rare side effect of colchicine in some patients. We report a case of myopathy in a patient with chronic kidney disease caused by high-dose colchicine, and then review literature on colchicine-induced myopathy, so as to provide some experience for the clinical diagnosis, treatment and medication safety. A 51-year-old male patient with 10 years of gout and 5 years of chronic kidney disease history and irregular treatment was admitted to the hospital with complaint of recurrent left wrist arthralgia and emerging lower extremities myalgia after intake of 40-50 mg colchicine in total within 20 days. Laboratory examinations showed significantly increased creatine kinase (CK) and then colchicine-induced myopathy was diagnosed preliminarily. After withdrawl of colchicine and implementation of hydration, alkalization and intramuscular injection of compound betamethasone, the symptoms of arthralgia and myalgia were relieved within 3 days and CK decreased to normal range gradually. According to literature reports, colchicine related myopathy was mostly characterized by proximal myasthenia and myalgia, accompanied by elevated CK level, which usually occurred days to weeks after initial administration of colchicine at the usual dosage in patients with renal impairment or a change in the underlying disease state in those receiving long-term therapy, and the features might remit within three to four weeks after the drug was discontinued. Electromyography of proximal muscles showed myopathy marked by abnormal spontaneous activity and muscle pathology waa marked by accumulation of lysosomes and autophagic vacuoles. Chronic kidney disease, liver cirrhosis, higher colchicine dose and concomitant cytochrome P450 3A4 (CYP3A4) inhibitors were associated with increased risk of myo-pathy. Based on the similar efficacy and lower adverse reaction rate compared with larger dosage, small dose of colchicine was recommended by many important current guidelines and recommendations in the treatment of gout. In consideration of potential risks, colchicine should be used with caution in patients with kidney or liver impairment, and in those taking CYP3A4 or P-glycoprotein inhibitors. For those patients, the drug dose should be adjusted and the latent adverse reactions should be monitored carefully.

Prognosis analysis of T 1 stage nasopharyngeal cancer with different lymph node and metastasis stages in the era of precision radiotherapy / 中华放射肿瘤学杂志

Objective:To evaluate the survival prognosis for T 1 stage nasopharyngeal carcinoma patients complicated with different stages of cervical lymph node metastasis, aiming to provide reference for optimizing the treatment plan. Methods:Clinical data of 413 patients in non-keratinizing carcinoma and undifferentiated locally early nasopharyngeal carcinoma (T 1N 0-3M 0-1) undergoing radiotherapy alone or radiochemotherapy in Department of Radiation Oncology of our hospital from January 2014 to December 2019 were retrospectively analyzed. The survival analyses were performed with Kaplan-Meier method and statistically compared using the log-rank test. Results:Of all patients, 291 were male, and 122 were female (aged from 9 to 78 years old) with a median age of 51 years old. All patients were diagnosed with T 1N 0-3M 0-1 nasopharyngeal carcinoma. In the TNM stage grouping system, 48(11.6%) patients were classified as stage Ⅰ (T 1N 0M 0), 158(38.2%) cases of stage Ⅱ(T 1N 1M 0), 162(39.2%) cases of stage Ⅲ(T 1N 2M 0), and 45(10.9%) cases of stage Ⅳ A to Ⅳ B(T 1N 3M 0/T 1N xM 1). Eight patients (1.9%) with stage Ⅳ B had metastasis at presentation. The lymph node positivity rate of all patients reached up to 88.1%. Seven patients received three-dimensional conformal radiotherapy, 371 cases of intensity-modulated radiotherapy and 35 cases of volumetric-modulated arc therapy. The 5-year overall survival rate was (95.9±1.2)% and with 100% for T 1N 0M 0 patients, (99.2±0.8)% for T 1N 1M 0 patients, (95.1±2.2)% for T 1N 2M 0 patients and (87.9±6.6)% for T 1N 3M 0 patients, respectively. Primary distant metastasis and N 3 stage were significantly correlated with poor prognosis (both P<0.05). The most common long-term side effect of radiotherapy was xerostomia with an incidence rate of 18.6%(17.9% for grade 1 toxicity), followed by hearing damage and tooth discomfort. Only 2 patients developed Grade Ⅲ toxic reactions, manifested as complete hearing loss. Conclusions:Although T 1 nasopharyngeal carcinoma patients have a high propensity of cervical node metastasis, favorable clinical prognosis can be obtained after radiotherapy alone. Moreover, the long-term side effects under precision radiation exert no severe effect upon the quality of life of patients.

Advances in treatment of narcolepsy / 浙江大学学报·医学版

Narcolepsy is the most common cause of excessive daytime sleepiness (EDS) following obstructive sleep apnea. Its treatment aims to reduce EDS and cataplexy, improve nighttime sleep disturbance, sleep paralysis and sleep-related hallucinations. Pitolisant (a histamine H3 receptor antagonist) and solriamfetol (a norepinephrine reuptake inhibitor) have recently been approved effective for narcolepsy in the United States and the European Union. Pitolisant has proved to be effective for both EDS and cataplexy. Besides being effective on EDS, solriamfetol seems to have advantages in abuse potential and withdrawal syndrome. As potential treatments for EDS and cataplexy associated with narcolepsy, several new drugs are being developed and tested. These new drugs include new hydroxybutyrate preparations (controlled release sodium hydroxybutyrate FT218, low sodium hydroxybutyrate JZP-258), selective norepinephrine reuptake inhibitor (AXS-12), and modafinil combined with astroglial junction protein inhibitor (THN102). This paper reviews the recently approved drugs and potential treatments for narcolepsy.

Comparison of GP and TP induction chemotherapy combined with concurrent radiochemotherapy for locally advanced nasopharyngeal carcinoma in the non-endemic of Northwest China: A prospective single center phase Ⅱ clinical study / 西安交通大学学报(医学版)

Objective: To explore the curative effect and adverse reactions of GP induction chemotherapy combined with chemoradiation contrast TP induction for local advanced nasopharyngeal carcinoma in the non-endemic of Northwest China, our center conducted the prospective, single-center, randomized controlled clinical research so as to clarify GP regimenvalue of induction chemotherapy in local advanced nasopharyngeal carcinoma treatment. Methods: We randomly assigned patients with newly diagnosed stage III-b patients to GP regimen of induction chemotherapy in combination with concurrent chemoradiotherapy and TP. Induction chemotherapy was given 2-3 cycles. Cisplatin regimen chemotherapy was given every 3 weeks and 1-3 cycles during radiotherapy. We compared the differences in tumor shrinkage and survival between the two groups and evaluated the toxicity and compliance of the two induction chemotherapy regimens. Results: A total of 72 patients were enrolled in this study, including 34 patients in GP group and 38 patients in TP group. The general clinical data of the two groups were balanced. Short-term efficacy evaluation showed no difference between the TP group and the GP group in terms of nasopharyngeal disease and ORR of cervical lymph nodes either after induction or concurrent chemoradiotherapy. The median follow-up time of the whole group was 74.8 months(0.8-108.9 months), and the 5-year DMFS of the GP group and the TP group was 83.9% and 76.5% (χ2=4.140, P=0.042), respectively. The difference was statistically significant. During the induction chemotherapy, the incidence of neutropenia, leukopenia and thrombocytopenia in the GP group was higher than that in the TP group (P<0.05). There was no difference between the two groups in other acute or late toxic or side effects. Results: In local advanced nasopharyngeal carcinoma in non-endemic regions of Northwest China, long-term efficacy of GP chemotherapy is better than that of TP chemotherapy. During the treatment, acute hematological toxicity of GP regimen group was heavier than that of TP group, but the compliance of subsequent chemoradiotherapy was not affected after symptomatic treatment. The late toxicity was equivalent to that of the two groups, and the treatment tolerance was acceptable.

Reversible blindness in a patient with closantel toxicity

To describe the optical coherence tomography (OCT) and electrophysiological changes in a case of closantel toxicity. A 25-year-old patient presented with sudden painless defective vision following intake of closantel. Visual acuity (VA) was counting fingers at 5 m in both eyes (BE). OCT revealed disruption of outer retinal layers and electroretinogram (ERG) and visual evoked potential (VEP) were subnormal in BE. The patient was treated with systemic corticosteroids, after which his VA improved to 6/9, OCT revealed preservation of central outer retinal layers, and ERG and VEP responses improved in BE. This is the first case report of successful treatment with systemic steroids for closantel-related reversible blindness.

Psychopharmacology in myasthenia gravis patients with focus on depression

Myasthenia gravis is an autoimmune disease with a potential to disrupt brain function and cause depression as a result of the disease itself or treatment side effect. Some biological and psychological mechanisms have been proposed for the correlations between myasthenia gravis and depression. Depression might present in patients myasthenia gravis, and it might complicate the course of the disease. Adequate treatment might not only improve the depression but might also impact the myasthenia gravis in general.

Observation of clinical efficacy of stereotactic body radiotherapy in 28 cases of large hepatocellular carcinoma / 中华放射肿瘤学杂志

Objective To observe the survival and side effects of stereotactic body radiotherapy (SBRT) in large hepatocellular carcinoma (HCC) patients.Methods Twenty-eight large HCC patients undergoing SBRT in 302 Military Hospital from November 1,2011 to January 31,2014 were observed.The prescribed dose was 39-61 Gy/3-9f.Among them,20 patients simultaneously received transcatheter arterial embolization.The overall survival (OS),progression-free survival (PFS) and local control (LC) rates were calculated by using Kaplan-Meier method.The influencing factors of OS were analyzed by Cox regression model The influencing factors of radiation-induced liver disease (RILD) were identified by using Logistic regression analysis.Results The 1-,2-,3-and 5-year OS rates were 75％,57％,54％ and 22％,respectively.The 1-,2-,3-and 5-year PFS rates were 59％,47％,36％ and 18％,respectively.The 1-,2-,3-and 5-year LC rates were 92％,86％,86％ and 86％,respectively.Four patients suffered from RILD and none died from RILD.Child-Pugh classification was the influencing factor of OS and RILD.Conclusion It is preliminarily believed that SBRT is an alternative and safe treatment for patients with large HCC.

Observation of clinical efficacy of stereotactic body radiotherapy in 28 cases of large hepatocellular carcinoma / 中华放射肿瘤学杂志

Objective@#To observe the survival and side effects of stereotactic body radiotherapy (SBRT) in large hepatocellular carcinoma (HCC) patients.@*Methods@#Twenty-eight large HCC patients undergoing SBRT in 302 Military Hospital from November 1, 2011 to January 31, 2014 were observed. The prescribed dose was 39-61 Gy/3-9f. Among them, 20 patients simultaneously received transcatheter arterial embolization. The overall survival (OS), progression-free survival (PFS) and local control (LC) rates were calculated by using Kaplan-Meier method. The influencing factors of OS were analyzed by Cox regression model. The influencing factors of radiation-induced liver disease (RILD) were identified by using Logistic regression analysis.@*Results@#The 1-, 2-, 3-and 5-year OS rates were 75%, 57%, 54% and 22%, respectively. The 1-, 2-, 3-and 5-year PFS rates were 59%, 47%, 36% and 18%, respectively. The 1-, 2-, 3-and 5-year LC rates were 92%, 86%, 86% and 86%, respectively. Four patients suffered from RILD and none died from RILD. Child-Pugh classification was the influencing factor of OS and RILD.@*Conclusion@#It is preliminarily believed that SBRT is an alternative and safe treatment for patients with large HCC.

Effect of omeprazole on plasma concentration and adverse reactions of capecitabine in patients with colon cancer / 中华肿瘤杂志

Objective@#To investigate the effect of omeprazole on plasma concentration, efficacy and adverse reactions of capecitabine in patients with colon cancer.@*Methods@#Seventy-two patients with colon cancer treated with capecitabine were analysed retrospective. The patients treated with capecitabine combined with omeprazole were identified as experimental group and the capecitabine treatment alone as control group.The differences of blood concentration and the side effects of capecitabine between these two groups were compared.@*Results@#The plasma concentration of 5-Fluorouracilum in experimental group was (126.25±50.59) μg/ml, without significant difference of (123.09±56.70) μg/ml in control group (P=0.121). The incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and hand-foot syndrome in experimental group were 13.8%, 0%, 0% and 19.4%, respectively. In control group, the incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and the hand-foot syndrome were 11.1%, 0%, 0% and 19.4%, respectively, without significant difference of experimental group (P>0.05). The incidence of acid reflux and heartburn in the control group was 72.2%, significantly higher than 44.4% of the experimental group (P<0.05). The objective response rate (ORR) and progression-free survival time (PFS) in these two groups were 30.6% and 33.3%, and 8.0 month and 8.5 month, respectively, without significant difference (P>0.05).@*Conclusion@#The intravenous omeprazole attenuates reflux and heartburn of colon cancer patients treated with capecitabine, without affecting its plasma concentration and side effects and has no impact on the PFS of these patients.