Early detection of circulating tumor DNA and successful treatment with osimertinib in thr790met-positive leptomeningeal metastatic lung cancer: A case report.

BACKGROUND: Patients diagnosed with non-small-cell lung cancer with activated epidermal growth factor receptor mutations are more likely to develop leptomeningeal (LM) metastasis than other types of lung cancers and have a poor prognosis. Early diagnosis and effective treatment of leptomeningeal carcinoma can improve the prognosis. CASE SUMMARY: A 55-year-old female with a progressive headache and vomiting for one month was admitted to Peking University First Hospital. She was diagnosed with lung adenocarcinoma with osseous metastasis 10 months prior to admittance. epidermal growth factor receptor (EGFR) mutation was detected by genomic examination, so she was first treated with gefitinib for 10 months before acquiring resistance. Cell-free cerebrospinal fluid (CSF) circulating tumor DNA detection by next-generation sequencing was conducted and indicated the EGFR-Thr790Met mutation, while biopsy and cytology from the patient's CSF and the first enhanced cranial magnetic resonance imaging (MRI) showed no positive findings. A month later, the enhanced MRI showed linear leptomeningeal enhancement, and the cytology and biochemical examination in CSF remained negative. Therefore, osimertinib (80 mg/d) was initiated as a second-line treatment, resulting in a good response within a month. CONCLUSION: This report suggests clinical benefit of osimertinib in LM patients with positive detection of the EGFR-Thr790Met mutation in CSF and proposes that the positive findings of CSF circulating tumor DNA as a liquid biopsy technology based on the detection of cancer-associated gene mutations may appear earlier than the imaging and CSF findings and may thus be helpful for therapy. Moreover, the routine screening of chest CT with the novel coronavirus may provide unexpected benefits.

Serum complement C1q level is associated with left ventricular hypertrophy induced by coarctation of the aorta: A retrospective observational study.

BACKGROUND: The complement system plays an important role in the development of left ventricular hypertrophy. Complement C1q is an initial component of the classical complement pathway and is related to many inflammatory diseases. We aimed to determine whether there was an association between serum complement C1q and left ventricular hypertrophy induced by coarctation of the aorta (CoA). METHODS: Based on whether CoA was combined with a large ventricular septal defect (VSD) or patent ductus arteriosus (PDA), the patients were divided into a simple CoA group (n = 15) and a complex CoA group (n = 13). Meanwhile, we selected simple large VSD (n = 14) patients and normal children (n = 28) as the control group. The serum complement C1q level was compared using immunity transmission turbidity among different groups. RESULTS: The preoperative content of C1q in the simple CoA group was significantly lower than that in the complex CoA group and normal group (96.97 ± 20.66 vs. 130.73 ± 35.78, 96.97 ± 20.66 vs. 156.21 ± 29.14, P < 0.05). There was no significant difference in the preoperative content of C1q between the complex CoA group and the large VSD group (P > 0.05). There was a negative correlation between the preoperative complement C1q content and the interventricular septal thickness and left ventricular posterior wall thickness (r = - 0.035, r = - 0.288, P < 0.05). The percentage of postoperative decrease in C1q in children with simple CoA or complex CoA was positively correlated with the time of cardiopulmonary bypass and aortic cross clamp, respectively (r = 0.797, r = 0.622, r = 0.898, r = 0.920, P < 0.05). There was no significant difference in the content of preoperative triglycerides (TG), total cholesterol (TCHO), high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C) among the different groups (P > 0.05). In the simple CoA group and complex CoA group, the preoperative complement C1q, TG, TCHO, HDL-C and LDL-C levels were significantly higher than those after the operation (P < 0.05). There was no significant correlation between preoperative complement C1q and TG, TCHO, HDL-C or LDL-C (P > 0.05). CONCLUSIONS: Complement C1q has an inhibitory effect on the formation of left ventricular hypertrophy, which may not be mediated by regulating lipid metabolism. During cardiac surgery, complement C1q may have a protective effect against myocardial injury.

Neuroprotective Effects of Early Brain Injury after Subarachnoid Hemorrhage in Rats by Calcium Channel Mediating Hydrogen Sulfide.

The present study explored the modulating apoptosis effect of hydrogen sulfide (H2S) in subarachnoid hemorrhage (SAH) rats and its exact mechanism. A rat SAH model established by intravascular puncturing was used for the present study. After giving NaHS (donor of H2S), an L-type calcium channel opener (Bay K8644), or a calcium channel agonist (nifedipine), the neurological function of the rats, associated pathological changes, and expression of apoptosis-related proteins (Bcl-2, Bax, and caspase-3) and microtubule-associated protein (MAP-2) were examined. The concentration of H2S and expression of cystathionine beta synthase in the hippocampus changed upon early brain injury (EBI) after SAH. Compared with the SAH group, the neurological function of the rats and microstructure observed by electron microscopy were better in the SAH + NaHS group and SAH + Bay K8644 group. It was observed that apoptosis was more obvious in the SAH group than in the control group and was alleviated in the SAH + NaHS group. Furthermore, the alleviating effect of NaHS was partially weakened by nifedipine, indicating that the effect of anti-apoptosis in H2S might be correlated with the calcium channel. The expression of Bax and caspase-3 was elevated, while the expression of Bcl-2 decreased in the SAH group but improved in the SAH + NaHS and SAH + Bay K8644 group. Compared with the SAH + NaHS group, the expression of pro-apoptotic proteins was higher in the SAH + NaHS + nifedipine group. Therefore, upon EBI following SAH, the H2S system plays an important neurological protective effect by modulating the function of the L-type calcium channel and inhibiting apoptosis.

Delayed diagnosis of acromegaly in a patient with focal segmental Glomerulosclerosis: a rare case report and literature review.

BACKGROUND: Experimental studies have demonstrated that hypersecretion of growth hormone (GH) is associated with development of glomerular sclerosis. However, clinical case of such condition is very rare. Here we presented a case of focal segmental glomerulosclerosis (FSGS) associated with acromegaly. CASE PRESENTATION: A 63-year-old man was diagnosed as nephrotic syndrome with minimal change disease for 2 years. Prednisone 1 mg/kg/day for 9 months led to no response. After admission, the second kidney biopsy indicated FSGS (NOS variant). On admission, his acromegalic features were noticed and he complained with a 20-year history of soft tissue swelling of hands and feet. Serum GH and insulin-like growth factor 1 (IGF-1) concentrations were both elevated significantly. An oral glucose tolerance test showed inadequate suppression of serum GH. The presence of a pituitary macroadenoma with a diameter of 1.4 cm by MRI confirmed the diagnosis of acromegaly. Then, the tumor was subtotally removed by trans-sphenoidal surgery. Partial remission of proteinuria was achieved 3 months after surgery and maintained during follow-up, with gradual reduce of corticosteroid. CONCLUSIONS: This rare case suggested that the hypersecretion of GH may participate, at least in part, in FSGS development and progression. Early diagnosis and treatment of acromegaly is beneficial.

[Surgical treatment of paraclinoid aneurysms].

OBJECTIVE: To explore the surgical treatment of paraclinoid aneurysms and evaluate the safety and efficacy of microsurgical clip and endovascular embolization of paraclinoid aneurysms. METHODS: The data of 28 patients with 30 paraclinoid aneurysms receiving surgical treatment were retrospectively analyzed. According to Barami classification, 4 aneurysms were type Ia, 5 aneurysms type Ib, 13 aneurysms type II, 4 aneurysms type IIIa, 1 aneurysm type IIIb, and 3 aneurysms type IV. In the study, 15 cases with 17 paraclinoid aneurysms received microsurgical treatment, of which 3 cases underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass firstly and then aneurysms were trapped. The other 13 cases received endovascular embolism, in which balloon assistant technology was performed in 3 cases and stent assistant technology in another 3 cases. RESULTS: All the 30 paraclinoid aneurysms were treated. One patient with bilateral paraclinoid aneurysms became blind after bilateral microsurgical procedures and another patient was unexceptedly dead 10 d after operation. Vasospasm resulting with cerebral infarction occurred in one case who received endovascular embolism, while two patients suffered from hydrocephalus. Ten cases of microsurgical group and 9 cases of interventional group were followed up with digital subtraction angiography, which disclosed that 9 cases of microsurgical group were clipped completely, while 7 aneurysms of interventional group were completely embolised. One aneurysm recurred and enlarged 12 months after stent assistant embolism, and after STA-MCA bypass and bilateral anterior cerebral artery anastomy and aneurysm insulation, the patient recovered well. When the patients were discharged, their Glasgow outcome scales showed that 18 cases were with 5, 8 with 4, 1 with 3 and 1 with 0. CONCLUSION: According to the classification, and with appropriate treatment, the patients with paraclinoid aneurysms will get good outcomes both with microsurgical clipping and with endovascular embolization.

[Application of superficial temporal artery to middle cerebral artery bypass in treatment of cerebral artery steno-occlusive disease].

OBJECTIVE: To explore the effect of superficial temporal artery to middle cerebral artery(STA-MCA) bypass in treatment of cerebrovascular disease. METHODS: Fifty-two patients with atherosclerotic carotid artery occlusion or middle cerebral artery occlusion or moyamoya disease were included in this study. There were both clinical ischemic manifestation and hemodynamic dysfunction detected by perfusion CT in all the patients. DSA and perfusion CT (PCT) were conducted before and after STA-MCA bypass in order to evaluate the change of hemodynamics and the state of anastomotic astium. The patients were followed-up to know if there was any complication or recurrent stroke. Modified Rankin scale (mRS) was used in assessing the state of neurological function. RESULTS: STA-MCA bypass was performed successfully in 50 patients, while anastomotic astium was found to be obstructed in 2 patients during operation and temporalis attachment was conducted immediately. Complications occurred in 4 patients, 2 with subdural hematoma, 1 with hematoma in contralateral basal ganglia, and 1 with poor wound healing. Postoperative DSA showed that anastomotic astium was opened well in 48 patients, while PCT displayed a significant improvement in both relative cerebral blood flow [rCBF,(37.79±9.76)mL/(min×100 g)vs.( 33.71±7.92)mL/(min×100 g),P<0.05] and the relative mean transmit time [rMTT,(8.49±1.97)s vs. (11.06±3.00)s,P<0.01]. mRS improved significantly in both the 3 month and 12 month follow-ups(1.37±0.66 vs. 1.58±0.64, 0.84±0.57 vs. 1.51±0.67,P<0.05). There was no ipsilateral stroke during the follow-up. CONCLUSION: STA-MCA bypass may improve the hemodynamic and neurological condition and prevent the recurrence of ischemic stroke in patients combined with occlusive cerebrovascular disease and hemodynamic disturbance.

[A case report of squamous cell carcinoma arising in a patient with meningomyelocele].

Meningomyelocele combined with squamous cell carcinoma is rare in literature. In this article, we report the clinical and treatment of a patient with meningomyelocele and squamous cell carcinoma and discuss its mechanism, clinical feature, therapy and prognosis.The patient was a 11-year-old Chinese boy.At the time of his birth he was noted to have a lumbosacral meningomyelocele, which was disrupted and the cerebral spinal fluid flew out when the child was six.The wound surface abrased and exudated repeatedly.Two months before admission,the meningomyelocele was disrupted again and the condition got worse.Inspection showed a meningomyelocele in the lower lumbar region 10 cm in diameter,consisting of a cauliflower-shaped swelling and a central crater containing black slough.The area smelled foul and was constantly draining serosanguineous fluid.Magnetic resonance imaging showed meningomyelocele associated with spinal dysraphism and tethered cord syndrome.After thorough preparation, operation was undertaken.A perpendicular skin incision,which was carried down to the lumbar aponeurosis,allowed the main bulk of the tumour to be undercut and removed.The quick frozen pathological examination confirmed that it was squamous cell carcinoma.The skin and subcutaneous tissue were further resected and the vertebral canal explored until frozen section showed the excision edge was clear.Skin closure was achieved by a bipedicle advancement flap,some 10 cm wide and the secondary defect was closed with a thigh skin graft.Histological examination showed that the massive outgrowth was a well-differentiated squamous cell carcinoma.The postoperative recovery was uneventful and the wounds healed by primary intention.Although meningomyelocele combined with squamous cell carcinoma is rare in literature,the possibility of cancerization should be considered when there is a long-term and non-healing ulcer (Marjolin ulcer) with foul smell in a meningomyelocele patient.

[Congenital bilateral perisylvian syndrome: a case report].

Congenital bilateral perisylvian syndrome (CBPS) is rare in literature, especially in China. In this article, we report the clinical and treatment of a patient with CBPS and discuss its mechanism, clinical features and therapy. This patient was a 28-year-old man. His main clinical features were pseudobulbar palsy, cognitive deficits and intractable epilepsy. MRI shows bilateral thickening of the cortex around the sylvian fissures which were deeper than normal and polymicrogyria. The electroencephalogram demonstrated slow spike in right temporal lobe and left frontal lobe. Rhythmal 4 Hz theta waves exist in left frontal and parietal lobe. As the epilepsy was poorly controlled by antiepileptic, section of the corpus callosum was carried out. After callosotomy, there was pronounced seizure reduction and intelligence development improvement. CBPS is characterized by pseudobulbar palsy, cognitive deficits, and bilateral perisylvian abnormalities in imaging studies. If intractable epilepsy is combined, callosotomy may be effective.