Clinical characteristics of gastrointestinal immune-related adverse events of immune checkpoint inhibitors and their association with survival

BACKGROUND Despite the popularity of immune checkpoint inhibitors(ICIs)in the treatment of advanced cancer,patients often develop gastrointestinal(GI)and non-GI immune-related adverse events(irAEs).The clinical characteristics and survival outcomes of GI-irAEs have not been fully elucidated in previous reports.This necessitates the evaluation of the impact of GI-irAEs on patients receiving ICI treatment.AIM To evaluate the clinical characteristics of GI-irAEs and their impact on survival in patients treated with ICIs.METHODS In this single-center,retrospective,observational study,we reviewed the records of 661 patients who received ICIs for various cancers at Nagoya University Hospital from September 2014 to August 2020.We analyzed the clinical characteristics of patients who received ICI treatment.We also evaluated the correlation between GI-irAE development and prognosis in non-small cell lung cancer(LC)and malignant melanoma(MM).Kaplan-Meier analysis was used to compare the median overall survival(OS).Multivariate Cox proportional hazards models were used to identify prognostic factors.A P value<0.05 was considered statistically significant.RESULTS GI-irAEs occurred in 34 of 605 patients(5.6%)treated with an anti-programmed cell death-1/programmed death-ligand 1(anti-PD-1/PD-L1)antibody alone and in nine of 56 patients(16.1%)treated with an anti-cytotoxic T-lymphocyte antigen 4(CTLA-4)antibody alone or a combination of anti-PD-1 and anti-CTLA-4 antibodies.The cumulative incidence and median daily diarrhea frequency were significantly higher in patients receiving anti-CTLA-4 antibodies(P<0.05).In 130 patients with MM,OS was significantly prolonged in the group that continued ICI treatment despite the development of GI-irAEs compared to the group that did not experience GI-irAEs(P=0.035).In contrast,in 209 patients with non-small cell LC,there was no significant difference in OS between the groups.The multivariate analyses showed that a performance status of 2-3(hazard ratio:2.406;95%confidence interval:1.125–5.147;P=0.024)was an independent predictive factor for OS in patients with MM.CONCLUSION Patients receiving anti-CTLA-4 antibodies develop GI-irAEs more frequently and with higher severity than those receiving anti-PD-1/PD-L1 antibodies.Continuing ICI treatment in patients with MM with GI-irAEs have better OS.

Remimazolam benzenesulfonate anesthesia effectiveness in cardiac surgery patients under general anesthesia

BACKGROUND Sedation with propofol injections is associated with a risk of addiction,but remimazolam benzenesulfonate is a comparable anesthetic with a short elimination half-life and independence from cell P450 enzyme metabolism.Compared to remimazolam,remimazolam benzenesulfonate has a faster effect,is more quickly metabolized,produces inactive metabolites and has weak drug interactions.Thus,remimazolam benzenesulfonate has good effectiveness and safety for diagnostic and operational sedation.AIM To investigate the clinical value of remimazolam benzenesulfonate in cardiac surgery patients under general anesthesia.METHODS A total of 80 patients who underwent surgery in the Department of Cardiothoracic Surgery from August 2020 to April 2021 were included in the study.Using a random number table,patients were divided into two anesthesia induction groups of 40 patients each:remimazolam(0.3 mg/kg remimazolam benzenesulfonate)and propofol(1.5 mg/kg propofol).Hemodynamic parameters,inflammatory stress response indices,respiratory function indices,perioperative indices and adverse reactions in the two groups were monitored over time for comparison.RESULTS At pre-anesthesia induction,the remimazolam and propofol groups did not differ regarding heart rate,mean arterial pressure,cardiac index or volume per wave index.After endotracheal intubation and when the sternum was cut off,mean arterial pressure and volume per wave index were significantly higher in the remimazolam group than in the propofol group(P<0.05).After endotracheal intubation,the oxygenation index and the respiratory index did not differ between the groups.After endotracheal intubation and when the sternum was cut off,the oxygenation index values were significantly higher in the remimazolam group than in the propofol group(P<0.05).Serum interleukin-6 and tumor necrosis factor-αlevels 12 h after surgery were significantly higher than before surgery in both groups(P<0.05).The observation indices were re-examined 2 h after surgery,and the epinephrine,cortisol and blood glucose levels were significantly higher in the remimazolam group than in the propofol group(P<0.05).The recovery and extubation times were significantly lower in the remimazolam group than in the propofol group(P<0.05);there were significantly fewer adverse reactions in the remimazolam group(10.00%)than in the propofol group(30.00%;P<0.05).CONCLUSION Compared with propofol,remimazolam benzenesulfonate benefited cardiac surgery patients under general anesthesia by reducing hemodynamic fluctuations.Remimazolam benzenesulfonate influenced the surgical stress response and respiratory function,thereby reducing anesthesia-related adverse reactions.

Observation of therapeutic effects of point application at Shenque(CV 8)plus moxa-salt hot compress for prevention of gastrointestinal adverse reactions after chemotherapy for non-Hodgkin Iymphoma

Objective:To observe the clinical efficacy of point application with De Huang(Rhizome Rhei Crude)powder at Shenque(CV 8)plus moxa-salt hot compress on the umbilicus for preventing gastrointestinal adverse reactions after chemotherapy for non-Hodgkin lymphoma(NHL).Methods:A total of 60 cases with NHL under chemotherapy were divided into two groups by hospitalization order,with 30 cases in each group.The control group was treated with routine nursing and the observation group was additionally given point application with Da Hueng(Rhizome Rhei Crude)powder plus moxa-salt hot compress on the umbilicus,to compare the effect in preventing gastrointestinal adverse reactions after chemotherapy between the two groups.Results:The occurrence rates of constipation,nausea,vomiting and poor appetite on the second day and fifth day after chemotherapy were obviously lower in the observation group than those in the control group,with statistically significant differences between the two groups(all P〈0.05).Conclusion;The point application with De Hueng(Rhizome Rhei Crude)powder at Shenque(CV 8)plus maxa-salt hot compress on the umbilicus can produce more significant efficacy in preventing the gastrointestinal adverse reactions after chemotherapy for NHL than routine nursing.Moreover,it is simple and easy to be used and popularized.

Oral pathology in inflammatory bowel disease

The incidence of inflammatory bowel diseases (IBD) - Crohn&#x02019;s disease (CD) and ulcerative colitis (UC) - has been increasing on a global scale, and progressively, more gastroenterologists will be included in the diagnosis and treatment of IBD. Although IBD primarily affects the intestinal tract, extraintestinal manifestations of the disease are often apparent, including in the oral cavity, especially in CD. Specific oral manifestations in patients with CD are as follows: indurate mucosal tags, cobblestoning and mucogingivitis, deep linear ulcerations and lip swelling with vertical fissures. The most common non-specific manifestations, such as aphthous stomatitis and angular cheilitis, occur in both diseases, while pyostomatitis vegetans is more pronounced in patients with UC. Non-specific lesions in the oral cavity can also be the result of malnutrition and drugs. Malnutrition, followed by anemia and mineral and vitamin deficiency, affects the oral cavity and teeth. Furthermore, all of the drug classes that are applied to the treatment of inflammatory bowel diseases can lead to alterations in the oral cavity due to the direct toxic effects of the drugs on oral tissues, as well as indirect immunosuppressive effects with a risk of developing opportunistic infections or bone marrow suppression. There is a higher occurrence of malignant diseases in patients with IBD, which is related to the disease itself and to the IBD-related therapy with a possible oral pathology. Treatment of oral lesions includes treatment of the alterations in the oral cavity according to the etiology together with treatment of the primary intestinal disease, which requires adequate knowledge and a strong cooperation between gastroenterologists and specialists in oral medicine.

Oxcarbazepine for trigeminal neuralgia may induce lower extremity weakness: A case report

BACKGROUND Although few studies have reported hyponatremia due to carbamazepine or oxcarbazepine in patients with epilepsy,no study has investigated cases of carbamazepine-or oxcarbazepine-induced hyponatremia or unsteady gait in patients with neuropathic pain.Herein,we report a case of oxcarbazepineinduced lower leg weakness in a patient with trigeminal neuralgia and summarize the diagnosis,treatment,and changes of clinical symptoms.CASE SUMMARY A 78-year-old male with a history of lumbar spinal stenosis was admitted to the hospital after he experienced lancinating pain around his right cheek,eyes,and lip,and was diagnosed with trigeminal neuralgia at the right maxillary and mandibular branch.He was prescribed oxcarbazepine(600 mg/d),milnacipran(25 mg/d),and oxycodone/naloxone(20 mg/10 mg/d)for four years.Four years later,the patient experienced symptoms associated with spinal stenosis,including pain in the lower extremities and unsteady gait.His serum sodium level was 127 mmol/L.Assuming oxcarbazepine to be the cause of the hyponatremia,oxcarbazepine administration was put on hold and the patient was switched to topiramate.At subsequent visit,the patient’s serum sodium level had normalized to 143 mmol/L and his unsteady gait had improved.CONCLUSION Oxcarbazepine-induced hyponatremia may cause lower extremity weakness and unsteady gait,which should be differentiated from those caused by spinal stenosis.

Clinical decision support for drug related events: Moving towards better prevention

Clinical decision support(CDS) systems with automated alerts integrated into electronic medical records demonstrate efficacy for detecting medication errors(ME) and adverse drug events(ADEs). Critically ill patients are at increased risk for ME, ADEs and serious negative outcomes related to these events. Capitalizing on CDS to detect ME and prevent adverse drug related events has the potential to improve patient outcomes. The key to an effective medication safety surveillance system incorporating CDS is advancing the signals for alerts by using trajectory analyses to predict clinical events, instead of waiting for these events to occur. Additionally, incorporating cutting-edge biomarkers into alert knowledge in an effort to identify the need to adjust medication therapy portending harm will advance the current state of CDS. CDS can be taken a step further to identify drug related physiological events, which are less commonly included in surveillance systems. Predictive models for adverse events that combine patient factors with laboratory values and biomarkers are being established and these models can be the foundation for individualized CDS alerts to prevent impending ADEs.

Polyarthritis,Tenosynovitis and Dry Eyes after Treatment by Immune Check-Point Inhibitors

Introduction: Immune checkpoint inhibitors targeting programmed death protein-1 and cytotoxic-T-lymphocyte-antigen-4 have revolutionized the treatment of various cancers. Despite their effectiveness, these therapies can lead to immune related adverse events. Observation: We reported a case of a 43- year-old white woman who was referred to our department for a management of acute polyarthritis. She was followed for a relapsing metastatic melanoma (stage IIIb) by surgery and Pembrolizumab, an immune checkpoint inhibitor targeting programmed death protein-1. After receiving her 4th cycle of this therapy she developed arthritis of the knees and the ankles, tenosynovitis and dry eyes with keratitis. After exclusion of other causes of polyarthritis such as connective-tissue disease, the diagnosis of rheumatologic immunerelated adverse events was retained. She was treated by 20 mg of prednisone daily, Pembrolizumab was discontinued. The evolution was favorable. Conclusion: Rheumatologic manifestations secondary to immune checkpoint inhibitors have been less well described in the literature. Their management requires the collaboration of oncologists and rheumatologists to limit the diagnostic delay and for an appropriate therapeutic choice according to their severity.

Effect of mild moxibustion on cancer-related fatigue,serum ghrelin and adiponectin in patients undergoing chemotherapy after colorectal cancer surgery

Objective To observe the effect of mild moxibustion on cancer-related fatigue,serum ghrelin and adiponectin in patients undergoing chemotherapy after colorectal cancer surgery.Methods Seventy patients were divided into a control group and an observation group according to the random number table method,with 35 cases in each group.Patients in both groups were treated with conventional FOLFOX4 chemotherapy regimen.Patients in the control group also received routine treatments such as symptomatic treatment of complications,health education,nutritional support,and exercise intervention.Patients in the observation group received mild moxibustion on the basis of interventions used in the control group.The Piper fatigue scale-revision(PFS-R),Karnofsky performance status(KPS)and spleen and kidney yang deficiency syndrome were scored,and serum ghrelin and adiponectin levels were measured before and after treatment.Results After treatment,total score of PFS-R in the control group did not change significantly(P>0.05),while in the observation group it was significantly reduced(P<0.05)and lower than that in the control group(P<0.05);KPS scores in both groups were increased(both P<0.05),and it was significantly higher in the observation group than in the control group(P<0.05);total score of spleen and kidney yang deficiency syndrome in the control group did not change significantly(P>0.05),while it was significantly reduced in the observation group(P<0.05)and lower than that in the control group(P<0.05);serum ghrelin and adiponectin levels in the control group had no significant changes(both P>0.05),but the levels were significantly increased in the observation group(both P<0.05)and higher than those in the control group(both P<0.05).Conclusion Based on the routine treatments,mild moxibustion can relieve fatigue,improve quality of life,and improve the symptoms of spleen and kidney yang deficiency in patients undergoing chemotherapy after colorectal cancer surgery,which may be related to the regulation of serum ghrelin and adiponectin levels.

Effect of acupoint massage plus acupoint sticking therapy for the stress reaction during postoperative anesthesia recovery period in patients undergoing nasal endoscopic surgery

Objective:To observe the effect of acupoint massage plus acupoint sticking therapy for the stress reaction during postoperative anesthesia recovery period in patients undergoing nasal endoscopic surgery.Methods:A total of 120 patients undergoing nasal endoscopic surgery were included,and all patients were under trachea intubation and general anesthesia.The patients were randomized into an observation group and a control group,with 60 patients in each group.Patients in the control group received conventional anesthesia resuscitation,while patients in the observation group received acupoint massage plus acupoint sticking therapy on the basis of conventional anesthesia resuscitation.Changes in the heart rate (HR),systolic blood pressure (SBP) and diastolic blood pressure (DBP) were observed at three time points including the end of the surgery (TO),the removal of the tracheal tube (T1) and 10 min after the removal of the tracheal tube (T2).The awakening and tube removal time,choking cough and restlessness,and adverse reactions (dizziness,nausea and vomiting) in 24 h post-surgery period were compared.Results:At T1 and T2,the comparisons of HR,SBP and DBP between the two groups showed statistical significance (all P＜0.05).Intra-group comparisons showed that the HR,SBP and DBP of the control group at T1 and T2 were significant different from those at TO (all P＜0.05).There were significant differences in the awakening time and tube removal time between the two groups (both P＜0.05).The incidences of choking cough and restlessness were 8.3％ and 3.3％ respectively in the observation group,versus 53.3％ and 30.0％ in the control group,and the between-group comparisons showed statistical significance (both P＜0.05).The incidences of dizziness,nausea and vomiting in 24 h post-surgery period were 3.3％,5.0％ and 0.0％ respectively in the observation group,versus 43.3％,33.3％ and 25.0％ in the control group,and the between-group comparisons showed statistical significance (all P＜0.05).Conclusion:Acupoint massage plus acupoint sticking therapy can effectively regulate the stress reaction during postoperative anesthesia recovery period in patients undergoing nasal endoscopic surgery,and maintain a stable internal environment.

Effect of treatment with Fufang Huangqi decoction(复方黄杞汤剂) on dose reductions and discontinuation of pyridostigmine bromide tablets, prednisone, and tacrolimus in patients with type Ⅰ or Ⅱ myasthenia gravis

OBJECTIVE: To investigate the clinical efficacy of Fufang Huangqi decoction(复方黄杞汤剂) in combination with pyridostigmine bromide tablets, prednisone, and tacrolimus in the treatment of type Ⅰ and Ⅱ myasthenia gravis(MG) through changes in the clinical symptom scores of 100 patients with type Ⅰ and Ⅱ MG. This study also aimed to examine dose reductions and discontinuation of these 3 Western medicines after administration of Fufang Huangqi decoction. METHODS: The clinical data on 100 patients with type I or II MG who were treated in the outpatient department of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, China, between June 2017 and June 2020 were collected. The patients were divided into 4 groups based on whether they had taken pyridostigmine bromide tablets, prednisone, and/or tacrolimus at the time of their hospital visit: the Fufang Huangqi decoction group(group A), the pyridostigmine bromide tablets + Fufang Huangqi decoction group(group B), the pyridostigmine bromide tablets + prednisone + Fufang Huangqi decoction group(group C), and the pyridostigmine bromide tablets + tacrolimus + Fufang Huangqi decoction group(group D). The average treatment time was(15.6 ± 11.5) months(range: 0.5-55 months). Changes in the clinical symptom scores of the 4 groups of patients after medication administration and dose reductions and discontinuation of the 3 Western medicines were analyzed. RESULTS: An overall effectiveness rate of 86.00% was achieved in the 100 patients after treatment for(15.6 ± 11.5) months(range 0.5-55 months). The effectiveness rates were 85.71% in group A, 88.24% in group B, 76.92% in group C, and 80.00% in group D. The dosage of pyridostigmine bromide was reduced for 69.12% of the patients in group B for the first time after(4.2 ± 4.1) months, and 45.59% of the patients in group B discontinued pyridostigmine bromide after(8.8 ± 6.1) months. The dosage of pyridostigmine bromide was reduced for 46.15% of the patients in group C for the first time after(5.3 ± 3.4) months, and 23.08% of the patients in group C discontinued pyridostigmine bromide after(19.8 ± 11.0) months;76.92% reduced hormone dosage after(2.8 ± 1.9) months, and 23.08% discontinued hormone treatment after(6.7 ± 2.9) months. The dosage of pyridostigmine bromide was reduced for 1 patient in group D after 1 month;this patient discontinued pyridostigmine bromide after 3 months and reduced tacrolimus dosage after 5 months. One patient in group D discontinued pyridostigmine bromide and tacrolimus on his own initiative at 0.5 months and took Fufang Huangqi decoction for 2 months without discontinuing Western medicine. CONCLUSION: Fufang Huangqi decoction is effective for the treatment of type Ⅰ and Ⅱ MG and improves the associated clinical symptoms. Moreover, this agent is conducive to dose reductions and discontinuation of basic Western medicines, thereby reducing the side effects experienced by patients.

Effect of acupoint sticking at Shenque （CV 8） for preventing spleen-stomach disharmony caused by venous analgesia pump

Objective： To observe the clinical effect of acupoint sticking of Chinese medicine at Shenque （CV 8） for preventing spleenstomach disharmony caused by venous analgesia pump. Methods： A total of 120 post-surgery patients using venous analgesia pump and also conforming to the inclusion criteria were randomized into 2 groups by the random number table. There were 58 patients in the control group who received conventional post-surgery nursing care, and there were 62 patients in the treatment group who received acupoint sticking at Shenque （CV 8） on the basis of conventional nursing care. After treatment, the incidences of postoperative nausea and vomiting, and abdominal bloating were measured. Results： The total incidence of nausea, vomiting and abdominal bloating in the treatment group was 11.3%, versus 39.7% in the control group, and the difference of the incidence between the two groups showed a statistical significance （P〈0.05）. In comparison of the severity of spleen-stomach dishormony which happened during 72 h after surgery, cases in the treatment group showed lower severity than those in the control group （P〈0.05）. Conclusion： Acupoint sticking at Shenque （CV 8） can effectively prevent spleen-stomach disharmony caused by venous analgesia pump, which will alleviate sufferings of the patients.

Post-marketing safety surveillance and reevaluation of Motherwort injection：A clinical study of 10094 cases

OBJECTIVE:To investigate the safety profiles of Motherwort injection(MI).METHODS:A multi-center,prospective and drugderived hospital intensive monitoring method was conducted to assess the safety of MI in real world applications.This study was based on a very large population after the injection was approved and marketed in China.All patients using the injection in participating hospitals were monitored to determine the incidence,pattern,severity and outcome of associated adverse events.RESULTS:The post-marketing surveillance was performed in 10 094 female patients from April to December,2015.The incidence of adverse drug reactions(ADRs) was 0.79‰(8/10 094).Among the 8 patients,the reported adverse events mainly included systemic abnormalities,such as fever,chills and eyelid edema;skin and appendages disorders,such as pruritus and rash;gastrointestinal disorders,such as nausea,abdominal distension and pain;heart rate and rhythm disorders,such as palpitation and increased heart rate.All of these ADRs were mild in severity.CONCLUSION:In this study the ADRs incidence rate of MI is very low,which supports that it is generally safe for use in obstetric and gynecological diseases.However,the total number of 8 ADRs recorded over a relatively short time span seems limited,and the low number of reports could not represent an absolute guarantee of safety.

Therapeutic observation of grain-sized moxibustion for chemotherapy-induced myelosuppression for non-small cell lung cancer

Objective: To observe the clinical efficacy of grain-sized moxibustion in treating chemotherapy-induced myelosuppression for non-small cell lung cancer (NSCLC) and its effect on quality of life (QOL). Methods: Eighty NSCLC patients admitted to the Inpatient Department of Zhejiang Cancer Hospital between September 2016 and March 2018 were recruited and divided into an observation group and a control group by random number method, with 40 cases in each group. The two groups both received chemotherapy with paclitaxel plus cisplatin (TP regimen). The control group received oral administration of leucogen tablets starting from the first day of chemotherapy, 20 mg each time, three times a day, for consecutive 14 d;the observation group was additionally given grain-sized moxibustion, once a day, five days per week at a two-day interval, until the fourteenth day. The myelosuppression severity was observed and compared between the two groups prior to chemotherapy, at the 3rd, 7th and 14th days of chemotherapy;the QOL in the two groups was evaluated before chemotherapy, at the 14th and 21st days of chemotherapy. Results: Regarding myelosuppression, the peripheral blood indicators increased significantly at the 3rd day of chemotherapy in both groups (P<0.05 or P<0.01);at the 7th and 14th days of chemotherapy, the peripheral blood indicators presented a decreasing tendency in the two groups, but the level in the observation group was still significantly higher than that before chemotherapy (P<0.01);at the 3rd, 7th and 14th days of chemotherapy, the peripheral blood indicators in the observation group were higher than those in the control group (P<0.05 or P<0.01);the occurrence rate of myelosuppression in the observation group was significantly lower than that in the control group (P<0.01). The QOL score in the observation group was markedly higher than that in the control group at the 14th and 21st days of chemotherapy (both P<0.05). Conclusion: Grain-sized moxibustion can effectively improve myelosuppression after chemotherapy for NSCLC, reducing its occurrence and enhancing the patient's QOL.

Scalp acupuncture combined with body acupuncture for 32 cancer cases with intractable hiccups after radiochemotherapy

Objective： To observe the therapeutic effect of scalp acupuncture combined with body acupuncture in treating cancer patients with intractable hiccups after radiochemotherapy. Methods; Thirty-two cancer patients with intractable hiccups after radiochemotherapy who met the inclusion criteria were selected. The Line 2 Lateral to Forehead （MS 3） of scalp stimulation areas as well as body acupoints including Danzhong （CV 17）, Zhongwan （CV 12）, bilateral Cuanzhu （BL 2）, Neiguan （PC 6）, Zusanli （ST 36） and Taichong （LR 3） were punctured. The treatment was given once a day, 5 treatments constituted a course, and the efficacy was evaluated after 2 treatment courses. Results： After 10 treatments, 26 cases were cured, 4 cases were improved, and 2 cases were invalid, and the total effective rate was 93.8%. Conclusion： Scalp acupuncture combined with body acupuncture in treating intractable hiccups in cancer patients after radiochemotherapy has reliable therapeutic effect, and it is easy-to-operate and can effectively alleviate the suffering of patients with less adverse reaction.