Recurrent spontaneous pneumothorax secondary to lung cystic lesions in a case of convalescent COVID-19: a case report and literature review.

BACKGROUND: While spontaneous pneumothorax has been documented in COVID-19 patients, reports on recurrent spontaneous pneumothorax due to cystic lesions in convalescent COVID-19 patients are scarce. The progression of these lung cystic lesions remains inadequately explored. CASE PRESENTATION AND LITERATURE REVIEW: An 81-year-old male, a non-smoker with a history of rheumatoid arthritis, presented with fever, cough, and expectoration for 14 days. Initially diagnosed with moderate COVID-19, he deteriorated to severe COVID-19 despite adherence to local treatment guidelines. Successive identification of three cystic lesions termed "bulla" or "pneumatocele", and one cystic lesion with air-fluid level, referred to as "pneumo-hamatocele" (PHC), occurred in his lungs. Gradual improvement followed anti-inflammatory therapy and optimal supportive care. However, on day 42, sudden worsening dyspnea prompted a computed tomography (CT) scan, confirming a right spontaneous pneumothorax and subcutaneous emphysema, likely due to PHC rupture. Discharge followed chest tube implementation for pneumothorax resolution. On day 116, he returned to the hospital with mild exertional dyspnea. Chest CT revealed recurrent right pneumothorax from a remaining cyst in the right lung. Apart from our patient, literature retrieval identified 22 COVID-19 patients with spontaneous pneumothorax due to cystic lesions, with a male predominance (95.6%; 22/23). Diagnosis of pneumothorax and lung cystic lesions occurred around day 29.5 (range: 18-35) and day 26.4 (± 9.8) since symptom onset, respectively. Except for one patient whose pneumothorax occurred on day seven of illness, all patients eventually recovered. CONCLUSIONS: Recurrent spontaneous pneumothorax secondary to lung cystic lesions may manifest in convalescent COVID-19 patients, particularly males with COVID-19 pneumonia. Chest CT around 2 to 3 weeks post-symptom onset may be prudent to detect cystic lesion development and anticipate spontaneous pneumothorax.

Clinical characteristics, treatment, and management of pembrolizumab induced hemophagocytic lymphohistiocytosis.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal adverse reaction to pembrolizumab. The clinical characteristics of pembrolizumab induced HLH are unknown. Exploring the clinical features of pembrolizumab induced HLH is crucial for the treatment and prevention of immune checkpoint inhibitor-induced HLH. METHODS: The literature related to pembrolizumab induced HLH was collected for retrospective analysis by searching the Chinese and English databases from inception until August 31, 2023. RESULTS: A total of 24 patients were included, including 17 men (70.8%) with a median age of 61 years (41,80). The time between the last infusion and the start of HLH ranged from 2 to 46 days, with a median time of 14 days. Fever (100%) was the most common symptom, accompanied by splenomegaly (14 cases, 58.3%) and hepatomegaly (6 cases, 25.0%). Laboratory examination revealed revealed anemia (18 cases, 75.0%), leukopenia (12 cases, 50.0%), thrombocytopenia (20 cases, 83.3%), hypertriglyceridemia (11 cases, 45.8%), hypofibrinogenemia (11 cases, 45.8%). decreased natural killer cell function (7 cases, 29.2%), and elevated soluble CD25(15 cases, 62.5%). All patients developed hyperferriinemia, with a median of 30,808 ng/mL (range 1303 ~ 100,000). Bone marrow biopsy showed hemophagocytosis (15 cases, 62.5%). After discontinuation of pembrolizumab and treatment with steroids, etoposide, intravenous immunoglobulin, cytokine blocking, and immunosuppression, 17 patients recovered or improved, and 5 patients eventually died. CONCLUSION: HLH should be suspected when unexplained fever, cytopenia, splenomegaly, and elevated aminotransferase occur in patients using pembrolizumab. Screening for risk factors before treatment with pembrolizumab may be necessary to prevent HLH.

Clinical Characteristics, Diagnosis, and Management of Aseptic Meningitis Induced by Trimethoprim-Sulfamethoxazole.

Objective: Trimethoprim sulfamethoxazole (TMP-SMX) is related to aseptic meningitis. However, a detailed description of its phenotype is lacking, which easily leads to misdiagnosis. The purpose of this article is to explore the clinical characteristics of TMP-SMX-induced aseptic meningitis (TSIAM). Methods: We collected literature related to TSIAM published before July 31, 2023, by searching Chinese and English databases. Data were extracted and analyzed descriptively. Results: The 55 patients were mostly female (60.0%), with a median age of 43 years (range: 2.5-90 years). The first onset time was from a few minutes to 3 months after administration, and the time of reonset was within 12 hours. Fever (98.2%), headache (78.2%), altered mental status (42.3%), nausea and vomiting (41.8%), and neck pain (34.5%) were the most common symptoms. In severe cases, patients presented with low blood pressure, seizures, unconsciousness, or coma. Typical cerebrospinal fluid analysis showed elevated white blood cell counts, with polymorphonuclear leukocytes predominating, elevated protein levels, and normal glucose levels. Brain imaging usually showed no abnormalities. Symptoms resolved rapidly after the discontinuation of TMP-SMX, within a median time of 2 days (range: 1, 60). Readministration of TMP-SMX led to another relapse of aseptic meningitis. Aseptic meningitis usually culminated in a full recovery, although one patient experienced permanent paraplegia. Conclusion: Clinicians should be aware that aseptic meningitis is a rare adverse effect of TMP-SMX. TMP-SMX should be discontinued in patients with TSIAM to reduce unnecessary testing and treatment, and readministration of TMP-SMX should be avoided.

Clinical characterization, treatment, and outcome of nivolumab-induced bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is a serious and rare complication of nivolumab. This study aimed to explore the clinical characteristics of nivolumab-induced BP and provide a reference for prevention and treatment of BP. METHODS: Literature on nivolumab-induced BP was collected for retrospective analysis by searching both Chinese and English databases as of July 31, 2023. RESULTS: Sixty patients were included, with a median age of 71 years (range 30 to 85 years), and they were predominantly male (78.3%). The median time to onset of BP was 31 weeks (range 2.4, 216) after nivolumab administration. Tense bullae (93.3%), pruritus (55.0%), and urticarial plaques (31.7%) were the most common manifestations. Lesions were found on the limbs (50.0%), trunk (38.3%), palms and soles (15.0%). Skin biopsies mainly showed subepidermal bullous/blister (50.0%) and eosinophilic infiltration (46.7%). Direct immunofluorescence showed mainly linear deposition of C3 and IgG (46.7%) at the dermal-epidermal junction. The patients stopped taking nivolumab and received systemic steroids (73.3%), topical steroids (63.3%), monoclonal antibodies (21.7%), doxycycline/minocycline (30.0%) and other treatments. Symptoms improved or were relieved in 88.4% of patients but did not improve in 8.3% of patients. CONCLUSION: Clinicians should closely monitor symptoms of BP in those receiving and discontinuing nivolumab, especially in older men. Early diagnosis and timely initiation of treatment may improve patient outcomes.

Amoxicillin-induced aseptic meningitis: clinical features, diagnosis and management.

OBJECTIVES: The clinical features of aseptic meningitis associated with amoxicillin are unknown. The main objective of this study was to investigate the clinical characteristics of amoxicillin-induced aseptic meningitis (AIAM) and provide a reference for clinical diagnosis and treatment. METHODS: AIAM-related studies were collected by searching the relevant databases from inception to October 31, 2022. RESULTS: AIAM usually occurred 3 h to 7 days after amoxicillin administration in 13 males and 9 females. Twenty-one patients (95.5%) had recurrent AIAM with a total of 62 episodes. Fever (19 cases, 86.4%) and headache (18 cases, 81.8%) were the most common symptoms. Typical cerebrospinal fluid (CSF) findings were leukocytosis (100%) with lymphocytic predominance (14 cases, 63.6%), elevated protein (20 cases, 90.1%), normal glucose (21 cases, 95.5%) and negative culture (21 cases, 100%). Brain magnetic resonance imaging showed mild meningeal enhancement in one patient. The symptoms resolved mainly within 1-4 days after drug discontinuation in all patients. CONCLUSION: Clinical attention should be given to the adverse effects of AIAM. The medication history of patients with suspected meningitis should be investigated to avoid unnecessary examination and antibiotic treatment.

Clinical characteristics, diagnosis and management of Sweet syndrome induced by azathioprine.

Sweet syndrome is a rare complication of azathioprine treatment with unelucidated clinical features. The purpose of this study was to investigate the clinical characteristics of azathioprine-induced Sweet syndrome (AISS) and provide a reference for diagnosis, treatment and prognosis. We collected relevant case reports of AISS by searching Chinese and English databases from 1960 to December 31, 2022, extracted the data and carried out a retrospective analysis. The median age of the 44 patients was 50 (range 9-89) years, and they included 32 males (72.7%). Fever (86.4%) and arthralgia (31.8%) were the most common clinical symptoms. The skin lesions were mainly pustules (54.5%), papules (40.9%), plaques (40.9%) and nodules (31.8%), which were mainly distributed on the extremities (54.5%), face (38.6%) and hands (36.4%). Laboratory examination revealed neutropenia (65.9%) as well as elevated C-reactive protein (63.6%) and erythrocyte sedimentation (40.9%) rates. Histopathology of the lesioned skin showed neutrophil infiltration (93.2%) and dermal edema (38.6%). Symptom relief was achieved at a median time of 7 days (range 2-28 days) after azathioprine discontinuation in all patients. Nine patients (20.5%) had skin lesions that recurred within 24 h after taking azathioprine again. Clinicians and pharmacists should grasp the regularity and characteristics of AISS and should not recommend the readministration of azathioprine, to avoid the recurrence of Sweet syndrome.

Clinical features, risk factors, diagnosis, and treatment of trimethoprim-sulfamethoxazole-induced hypoglycemia.

Objective: Hypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical characteristics, risk factors, treatment, and prognosis of TMP-SMX-induced hypoglycemia. Methods: Case reports and series of TMP-SMX-induced hypoglycemia were systematically searched using Chinese and English databases. Primary patient and clinical information were extracted for analysis. Results: A total of 34 patients were reported from 31 studies (16 males and 18 females). The patients had a median age of 64 years (range 0.4-91), and 75.8% had renal dysfunction. The median duration of a hypoglycemic episode was six days (range 1-20), and the median minimum glucose was 28.8 mg/dL (range 12-60). Thirty-two patients (97.0%) showed neuroglycopenic symptoms, with consciousness disturbance (30.3%) and seizure (24.2%), sweating (18.2%), confusion (15.2%), asthenia (12.1%) being the most common symptoms. Fifteen patients (44.1%) had elevated serum insulin levels, with a median of 31.8 µU/mL (range 3-115.3). C-peptide increased in 13 patients (38.2%), with a median of 7.7 ng/mL (range 2.2-20). Complete recovery from symptoms occurred in 88.2% of patients without sequelae. The duration of hypoglycemia symptoms was 8 hours to 47 days after the intervention. Interventions included discontinuation of TMP-SMX, intravenous glucose, glucagon, and octreotide. Conclusion: Hypoglycemia is a rare and serious adverse effect of TMP-SMX. Physicians should be aware of this potential adverse effect, especially in patients with renal insufficiency, increased drug doses, and malnutrition.

An Alternating Magnetic Field-Controlled Drug Delivery System Based on 4,4'-Azobis (4-cyanovaleric Acid)-Functioned Fe3O4@Chitosan Nanoparticles.

Herein, we designed chitosan-coated Fe3O4 nanocomposites for the control release of drugs by an alternating magnetic field (AMF). The chitosan-coated Fe3O4 nanoparticles (Fe3O4@CS) were prepared by a alkaline co-precipitation method, and then, the model drug toluidine blue (TB) was covalently grafted onto the surface of the nanocomposite by a two-step amide reaction with the thermosensitive molecule 4,4'-azobis (4-cyanovaleric acid) (ACVA) as the linker group. The prepared nanocomposites were superparamagnetic and showed high magnetization saturation (about 54.0 emu g-1). In vitro hydrothermal release studies showed that most parts of the TB would be effectively enclosed within the nanocarriers at lower ambient temperatures (23 or 37 °C) due to the molecular bonding of ACVA. The results of kinetic fitting of hydrothermal release data showed that TB released from nanoparticles followed first-order kinetics (R2 > 0.99) and the Korsemeyer-Peppas model (R2 > 0.99, n < 0.5). Most importantly, a single magnetron release experiment demonstrated an approximately linear relationship between the cumulative release of the drug and the duration of action of AMF (R2 = 0.9712). Moreover, the increase in the cumulative release of the drug can be controlled by controlling the switch of the AMF generation device. Therefore, the ACVA-modified Fe3O4@CS nanocarrier designed in this study is a promising model for drug delivery that enables the control of drug release dose by AMF.

Clinical characteristics, management, and outcome of eosinophilic pneumonia associated with daptomycin

Objective: The association between daptomycin exposure and eosinophilic pneumonia (EP) is mainly based on case reports. The purpose of this study was to evaluate the clinical characteristics and provide more evidence for better identify and management of daptomycin-induced eosinophilic pneumonia in clinical practice.MethodsLiterature from 1991 to October 31, 2021 on EP induced by daptomycin were collected for retrospective analysis.ResultsA total of 47 patients (40 male and 7 female) from 35 studies were included. The median age was 67 years (range 28–89), and 78.7% of patients were ≥60 years. Daptomycin was mainly used in patients undergoing osteoarticular infections (63.8%). Typical initial symptoms were fever (91.5%), cough (55.3%) and dyspnea (59.6%). The median onset time of symptom was 3 weeks. EP recurred in 14.9% of patients after the re-administration of daptomycin, and 57.1% of EP recurred within 24h. Most cases were accompanied by marked accumulation of eosinophils in peripheral (41 cases) and/or bronchoalveolar lavage fluid (27 cases). The main radiological features were pulmonary infiltration, ground glass opacity or consolidation in CT/CXR. All patients had symptom resolution after discontinuation of daptomycin except for one patient died due to the progression of the primary disease, the median time to symptoms relief was 3 days. Corticosteroids have been shown to help symptoms relief in some cases (59.6%).ConclusionDaptomycin-induced eosinophilic pneumonia is a rare and serious complication. Physicians should consider eosinophilic pneumonia as a differential diagnosis when receiving daptomycin therapy, particularly in elderly male patients. (AU)

Objetivo: La asociación entre la exposición a daptomicina y la neumonía eosinofílica (NE) se basa principalmente en informes de casos. El propósito de este estudio fue evaluar las características clínicas y proporcionar más evidencia para una mejor identificación y tratamiento de la NE inducida por daptomicina en la práctica clínica.MétodosSe recopiló literatura médica desde 1991 hasta el 31 de octubre de 2021 sobre NE inducida por daptomicina para un análisis retrospectivo.ResultadosSe incluyeron un total de 47 pacientes (40 hombres y 7 mujeres) de 35 estudios. La mediana de edad fue de 67 años (rango 28-89), y el 78,7% de los pacientes tenían≥60 años. La daptomicina se utilizó principalmente en pacientes con infecciones osteoarticulares (63,8%). Los síntomas iniciales típicos fueron fiebre (91,5%), tos (55,3%) y disnea (59,6%). La mediana del tiempo de aparición de los síntomas fue de 3 semanas. La NE reapareció en el 14,9% de los pacientes después de la readministración de daptomicina, y el 57,1% lo hizo dentro de las primeras 24h. La mayoría de los casos se acompañó de una marcada acumulación de eosinófilos en tejidos periféricos (91,1%)/pulmonares (7 casos) y/o líquido de lavado broncoalveolar (27 casos). Las principales características radiológicas fueron infiltración pulmonar, opacidad «en vidrio deslustrado» o consolidación en TC/CXR. Todos los pacientes tuvieron una resolución de los síntomas después de la interrupción de la daptomicina, excepto uno que falleció debido a la progresión de la enfermedad primaria; la mediana de tiempo hasta el alivio de los síntomas fue de 3 días. Se ha demostrado que los corticoides ayudan al alivio de los síntomas en algunos casos (59,6%).ConclusiónLa NE inducida por daptomicina es una complicación rara y grave. Los médicos deben considerar la NE como un diagnóstico diferencial cuando un paciente recibe tratamiento con daptomicina, particularmente en varones de edad avanzada. (AU)

Analysis of the clinical characteristics of dabigatran-induced oesophagitis.

OBJECTIVES: Dabigatran-induced oesophagitis has emerged in recent years. However, the incidence and clinical characteristics of patients with dabigatran-induced oesophagitis have not yet been clarified. The aim of this study was to examine the clinical characteristics of the disease. METHODS: A retrospective analysis was undertaken of the literature on dabigatran-induced oesophagitis in Chinese and English from 2008 onwards. RESULTS: There were 20 men (74.07%) and seven women (25.93%) in the study; their median age was 75 years (range 37-90). The main clinical symptoms were dysphagia (42.31%), odynophagia (26.92%), retrosternal pain (23.08%) and heartburn (23.08%). Endoscopy mainly showed sloughing mucosal casts (14 cases, 56%), ulcers (8 cases, 32%) and erosion (6 cases, 24%). The main injury sites were the mid to lower oesophagus (32%) and the mid oesophagus (32%). Withdrawal of dabigatran or giving the correct medication regimen resulted in rapid recovery of clinical symptoms from 1 day in some patients and up to 4 weeks, and mucosal recovery (2-5 weeks) in a median time of 3 weeks (range 0.29-48) in all patients. CONCLUSIONS: Oesophagitis is a rare complication of dabigatran with a good prognosis. Patients should be given proper medication instructions to prevent the occurrence of dabigatran-induced oesophagitis.

Clinical characteristics, management, and outcome of eosinophilic pneumonia associated with daptomycin.

OBJECTIVE: The association between daptomycin exposure and eosinophilic pneumonia (EP) is mainly based on case reports. The purpose of this study was to evaluate the clinical characteristics and provide more evidence for better identify and management of daptomycin-induced eosinophilic pneumonia in clinical practice. METHODS: Literature from 1991 to October 31, 2021 on EP induced by daptomycin were collected for retrospective analysis. RESULTS: A total of 47 patients (40 male and 7 female) from 35 studies were included. The median age was 67 years (range 28-89), and 78.7% of patients were ≥60 years. Daptomycin was mainly used in patients undergoing osteoarticular infections (63.8%). Typical initial symptoms were fever (91.5%), cough (55.3%) and dyspnea (59.6%). The median onset time of symptom was 3 weeks. EP recurred in 14.9% of patients after the re-administration of daptomycin, and 57.1% of EP recurred within 24h. Most cases were accompanied by marked accumulation of eosinophils in peripheral (41 cases) and/or bronchoalveolar lavage fluid (27 cases). The main radiological features were pulmonary infiltration, ground glass opacity or consolidation in CT/CXR. All patients had symptom resolution after discontinuation of daptomycin except for one patient died due to the progression of the primary disease, the median time to symptoms relief was 3 days. Corticosteroids have been shown to help symptoms relief in some cases (59.6%). CONCLUSION: Daptomycin-induced eosinophilic pneumonia is a rare and serious complication. Physicians should consider eosinophilic pneumonia as a differential diagnosis when receiving daptomycin therapy, particularly in elderly male patients.

Clinical features, diagnosis, and management of pembrolizumab-induced myasthenia gravis.

Myasthenia gravis (MG) is a rare but life-threatening adverse event with pembrolizumab. What is known about pembrolizumab-induced MG is largely based on case reports. This analysis collected pembrolizumab-induced MG cases from Chinese and English databases published from September 1, 2014, to June 30, 2022. Demographic and clinical information of the patients, management, and outcome data were collected and analyzed. Sixty-five patients with a median age of 73 years (range 30-86), including 43 male patients (66.2%), were included. Eight patients (12.3%) with prior MG experienced worsening symptoms after receiving pembrolizumab. The median time to the onset of MG was four weeks (range 0.7-27). The most common symptoms were ptosis (81.5%, 53 patients), diplopia (50.8%, 33 patients), dyspnea (44.6%, 29 patients), trunk or peripheral weakness (43.1%, 28 patients), and dysphagia (30.8%, 20 patients). Concurrent myositis and myocarditis occurred in 13 (20.0%) and 17 patients (26.2%). Pembrolizumab was discontinued in 63 patients (96.9%). Forty-four patients (67.7%) received combination therapies based on steroids (intravenous immune globulin, plasmapheresis, or immunosuppressants). Twenty-seven patients (41.5%) had symptoms completely recovered. Fourteen patients (21.5%) died from immunotoxicity or primary cancers. Clinicians should consider the possibility of pembrolizumab-induced MG, especially during the first eight weeks of therapy. Patients should be treated as early as possible, regardless of the severity of the initial symptoms.

Analysis of the clinical characteristics of tigecycline-induced hypofibrinogenemia.

Knowledge regarding the association between hypofibrinogenemia and tigecycline is based mainly on case reports. However, the clinical features of tigecycline-induced hypofibrinogenemia are unclear. We collected 20 patients (16 males and 4 females) with tigecycline-induced hypofibrinogenemia by searching the Chinese and English databases from June 2005 to May 2021, with a median age of 63.5 years (range 39∼90 years). Hypofibrinogenemia developed at a median of 9 days (range 2∼35 days). Most patients had no typical clinical manifestations, and only a few patients had bleeding and ecchymosis. Fibrinogen levels gradually decreased from 3.98 ± 2.05 g/L to 0.87 ± 0.45 g/L (P = 0.000), and the activated partial thromboplastin time (APTT) increased from 38.26 ± 8.80 s to 83.43 ± 47.23 s (P = 0.002). Fibrinogen levels in all patients recovered to the normal range within a median of 4 days (range 1∼12 days) after tigecycline cessation. Our results suggest that fibrinogen levels should be closely monitored in patients treated with tigecycline, specifically patients who may have renal insufficiency or patients with long-term use.

Effect of miRNA-200b on the proliferation of liver cancer cells via targeting SMYD2/p53 signaling pathway. / MiR-200b通过靶向调控SMYD2/p53信号通路抑制肝癌细胞增殖（英文）.

OBJECTIVES: Our previous study has verified that high level of SET and MYND domain-containing protein 2 (SMYD2) plays an important role in acquiring aggressive ability for liver cancer cells in hepatocellular carcinoma. MiR-200b as a tumor suppressor gene involves in a variety of cancers. This study aims to investigate the correlation between miR-200b and SMYD2 in hepatocellular carcinoma and the underlying mechanism. METHODS: Firstly, the levels of SMYD2 and miR-200b in hepatocellular carcinoma tissues and matched adjacent non-tumor liver tissues were tested with real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Secondly, we evaluated the interaction between miR-200b and SMYD2 using dual-luciferase reporter assay. Thirdly, we elucidated the effect of miR-200b on SMYD2 and its downstream targets p53/CyclinE1. Finally, we silenced SMYD2 in hepatocellular carcinoma cell lines to investigate its effect on tumor proliferation and cell cycle progression, and further confirmed the correlation among SMYD2 and p53/CyclinE1. RESULTS: Compared with the matched adjacent non-tumor liver tissues, miR-200b was obviously decreased, and SMYD2 was significantly increased in hepatocellular carcinoma (both P<0.05). Spearman's rank correlation revealed that miR-200b expression was negatively correlated with SMYD2 (P<0.01). Computer algorithm and dual-luciferase reporter assay revealed that miR-200b directly targeted and suppressed SMYD2 in HEK 293T cells. The down-regulated miR-200b expression promoted hepatoma cell proliferation (P<0.05) and increased SMYD2 expression(P<0.01), while the up-regulated expression of miR-200b had an opposite effect. The knockdown of SMYD2 suppressed the proliferation of MHCC-97L cells (P<0.01), down-regulated CyclinE1, and up-regulated p53 expression (both P<0.05). CONCLUSIONS: MiR-200b is involved in hepatocellular carcinoma progression via targeting SMYD2 and regulating SMYD2/p53/CyclinE1 signaling pathway and may be used as a potential target for hepatocellular carcinoma treatment.

Clinical features, diagnosis and management of amoxicillin-induced Kounis syndrome.

Background: The available evidence suggests that amoxicillin is often associated with the occurrence of Kounis syndrome (KS). The purpose of this study is to explore the clinical characteristics of KS induced by amoxicillin. Methods: We searched for case reports of amoxicillin-induced KS through Chinese and English databases from 1972 to May 2022. Results: A total of 33 patients with KS were included, including 16 patients (48.5%) receiving amoxicillin treatment and 17 patients (51.5%) receiving amoxicillin-clavulanate. The median age was 58 years (range 13-82), 75.8% were from Europe and 81.8% were male. Nearly 70% of KS patients develop symptoms within 30 min after administration. Chest pain (63.6%) and allergic reaction (75.8%) were the most common clinical manifestations. Diagnostic evaluation revealed elevated troponin (72.7%), ST-segment elevation (81.2%) and coronary artery stenosis with thrombosis (53.6%). Thirty-two (97.0%) patients recovered completely after discontinuation of amoxicillin and treatments such as steroids and antihistamines. Conclusion: KS is a rare adverse reaction of amoxicillin. Amoxicillin-induced KS should be considered when chest pain accompanied by allergic symptoms, electrocardiogram changes and or elevated levels of myocardial injury markers. Therapeutic management of KS requires simultaneous treatment of cardiac and allergic symptoms. Epinephrine should be used with caution in patients with suspected KS.

Clinical features, diagnosis and management of cephalosporin-induced acute generalized exanthematous pustulosis.

WHAT IS KNOWN AND OBJECTIVE: Acute generalized exanthematous pustulosis (AGEP) is a serious and rare adverse reaction of cephalosporins. We aimed to describe the clinical features of cephalosporin-induced AGEP and provide a reference for rational clinical use of cephalosporins. METHODS: We systematically searched Chinese and English databases for cephalosporin-induced TGEP-related case reports, retrospective studies, clinical studies, and review articles published before May 2022. RESULTS AND DISCUSSION: A total of 43 patients from 35 articles were eligible, of which 28 (65.1%) were female, with a median age of 69 years. A total of 11 cephalosporins were suspected, the most commonly involved were ceftriaxone (41.9%), cephalexin (16.3%), and cefepime (9.3%). AEGP erupted primarily within 14 days after administration, manifested as nonfollicular pustules on an erythematous base, distributed favourably to the extremities (44.2%), trunk (23.3%), face (23.3%), and could involve the oral mucosa (11.6%). During AGEP resolution, the affected area had desquamation (39.5%). The acute phase of the disease may be accompanied by fever (>38.0°C) and elevated neutrophil count (>7500/mm3 ). Histology of AGEP showed subcorneal pustules (56.3%), intraepidermal cavernous pustules (37.5%), with papillary dermal edema (37.5%), containing neutrophils and eosinophilic infiltration (71.9%). After drug discontinuation, the median time to resolution of AGEP symptoms was 10 days (range 2, 90). WHAT IS NEW AND CONCLUSION: Cephalosporin-induced AGEP is rare and should be properly diagnosed. This serious cutaneous adverse reaction is self-limiting and has a favourable prognosis, usually resolves with drug interruption, and may require additional interventions, such as topical steroids.

Analysis of Clinical Features of Non-steroidal Anti-inflammatory Drugs Induced Kounis Syndrome.

Background: Current knowledge of Kounis syndrome induced by non-steroidal anti-inflammatory drugs (NSAIDs) is based on case reports. This study aimed to investigate the clinical features of Kounis syndrome. Methods: Case reports of the NSAIDs-induced Kounis syndrome were analyzed by searching Chinese and English databases from 1 January 1950 to 31 January 2022. Results: The median age of the 45 included patients (28 women) was 51 years (20-80 years). NSAIDs that were the most frequently involved were diclofenac (26.7%, 12/45), metamizole (15.6%, 7/45), and aspirin (13.3%, 6/45). Kounis syndrome occurred mainly within 30 min after administration, with a maximum latency of 1 month. Chest pain (75.6%, 34/45), dyspnea (33.3%, 15/45), and allergic reactions (44.4%, 20/45) were the most common clinical manifestations. Thirty patients (66.7%) had an ST-segment elevation on the electrocardiogram. Echocardiogram and coronary angiography showed abnormalities in 21 patients (75%, 21/28) and 15 patients (37.5%, 15/40). Forty-four patients (97.8%) had a good prognosis after treatment with steroids, antihistamines, and vasodilators. Conclusion: The possibility of Kounis syndrome should be considered in the presence of coronary artery disease symptoms when taking NSAIDs. Kounis syndrome can be life-threatening. It is essential to identify and treat Kounis syndrome correctly.

Clinical features, diagnosis, and management of dasatinib-induced nephrotic syndrome.

Knowledge of dasatinib-induced nephrotic syndrome is largely based on case reports. The clinical features of dasatinib-induced nephrotic syndrome are unknown. We collected case reports of 25 patients with nephrotic syndrome and analyzed their clinical characteristics. Overall, the onset of nephrotic syndrome ranged from 10 days to 5 years after dasatinib administration. Nine patients (36.0%) had clinical symptoms, mainly periorbital edema and lower-extremity edema. Serum albumin ranged from 1.2 g/dL to 3.7 g/dL in 10 patients (38.5%). The 24-h urine protein values ranged from 3.54 g/day to 118 g/day. Kidney biopsy of 13 patients (52.0%) mainly showed focal foot process effacement, mesangial hyperplasia, endothelial cell damage and focal segmental glomerulosclerosis. Proteinuria resolved or recovered after dasatinib discontinuation or dose reduction or switching to other tyrosine kinase inhibitors (TKIs).

Analysis of Clinical Features of Kounis Syndrome Induced by Cephalosporin.

Background: Cephalosporins are an increasingly encountered cause of Kounis syndrome. The present study examined the clinical features of cephalosporin-induced Kounis syndrome and provided references for diagnosis, prevention, treatment, and prognosis. Methods: We collected cephalosporin-induced Kounis syndrome case reports by searching Chinese and English databases from the establishment of the database to October 31, 2021. Results: Twenty-five patients (17 males and eight females) were included, with a median age of 61 years (range 33-92). Cephalosporins were administered via oral, intravenous and intramuscular routes. All reactions occurred within 30 min, except in two patients. Fourteen patients experienced chest pain, 19 experienced hypotension, 16 had cutaneous reactions, 10 had respiratory symptoms, and seven had gastrointestinal symptoms. Thirteen patients had elevated troponin levels, and eight patients had elevated serum tryptase levels. The electrocardiogram showed ST-segment elevation in 13 patients, depression in four patients, and elevation and depression in six patients. Coronary angiography showed normal results in 12 patients and abnormal results in 13 patients. The skin prick test was positive for cephalosporin in three patients. Twenty-four of the 25 patients recovered after being given anti-allergic and acute coronary syndrome treatment, and there was one death. Conclusions: Kounis syndrome is a serious adverse reaction to cephalosporin. Clinicians should consider Kounis syndrome in every patient receiving cephalosporin and presenting with acute chest pain or anaphylactic symptoms.

Analysis of the clinical characteristics of olanzapine-induced acute pancreatitis.

Numerous case reports of acute pancreatitis (AP) induced by olanzapine have been published. Little is, however, known about the clinical features of olanzapine-induced AP. The aim of the study was to explore the clinical characteristics of olanzapine-induced AP. We collected literature on AP cases induced by olanzapine from 1996 to April 2021 for retrospective analysis in Chinese and English. The median time to onset of olanzapine-induced acute pancreatic symptoms was 12 (range = 0.86-216) weeks in 25 patients. The clinical features of AP range from asymptomatic elevation of blood amylase/lipase levels to digestive system symptoms (abdominal pain, vomiting, and nausea) and even death in a small number of patients. Laboratory tests showed varying degrees of elevated serum amylase and lipase levels, along with high blood sugar and high triglyceride levels in some patients. Computed tomography showed acute edematous pancreatitis, acute hemorrhagic pancreatitis, and acute necrotizing pancreatitis in the patients. The patients' symptoms were completely relieved and high triglyceride levels gradually returned to normal levels after olanzapine was stopped. Some patients with hyperglycemia still needed hypoglycemic therapy. AP is a rare adverse effect of olanzapine. Clinicians should be aware of such complications and monitor pancreatin.