Toripalimab (anti-PD-1) versus high-dose interferon-α2b as adjuvant therapy in resected mucosal melanoma: a phase II randomized trial.

BACKGROUND: No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only ∼5 months after surgery alone. This phase II trial aimed to compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM. PATIENTS AND METHODS: From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 [95% confidence interval (CI) 8.31-19.02] months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms [hazard ratio (HR) 1.00; 95% CI 0.65-1.54]. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients' actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%). CONCLUSIONS: Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.

[Source investigation on a familiar cluster of coronavirus disease 2019 in Dandong city of Liaoning Province].

To Track the source of the infection through an investigation of a clustering of coronavirus disease 2019(COVID-19), and provide scientific basis and Strategy for the effective control of the aggregated epidemic situation of COVID-19. Field epidemiological method was used to survey the cases and related close contacts in a family clustering epidemic of COVID-19 in Dandong city of Liaoning Province. We obtained survey data for a descriptive analysis.Real time RT-PCR technique was used to detect 2019-nCoV nucleic acid in samples collected from cases and related close contacts combined with serum specific antibody detection. A total of 3 confirmed cases and 2 asymptomatic infection cases were discovered in the clustering epidemic, with 34 close contacts.Of eight close family contacts visiting from other province, one patient was on the same flight as the confirmed case, and her antibody IgG was positive. The family clustering was caused by past infection case who visited her friend through Wuhan from other provinces to local area.

[Impact of first-line chemotherapy on renal function in patients with advanced upper tract urothelial carcinoma].

Objective: To observe the impact of first-line chemotherapy on renal function in patients with unresectable/metastatic upper tract urothelial carcinoma(UTUC). Methods: A total of 222 (130 males and 92 females) unresectable/metastatic upper tract urothelial carcinoma patients were included in the study between January 2005 and May 2017, with age of 29 to 87 (62.4±10.1) years old. The serum creatinine level and estimated glomerular filtration rate (eGFR) were compared before and after first-line chemotherapy. And predictive factors for decreased renal function were analyzed in logistic regression model. Results: After the first-line chemotherapy, the average serum creatinine level increased, with a median changing value of 1.5 µmol/L. Howerver, the eGFR improved, with a median changing value of 0.5 ml·min-1· (1.73 m2)-1, but the differences were not statistically significant (all P>0.05). In 149 patients who were treated with cisplatin-based chemotherapy, the average serum creatinine level increased by 1.31 µmol/L and eGFR improved by 0.14 ml·min-1·(1.73 m2)-1, but the differences were not statistically significant (P>0.05). In multivariate logistic regression model, age more than and equal to 60 years old (OR=0.88, P=0.745) and cisplatin-based chemotherapy (OR=0.95, P=0.893) did not increase the risk of renal dysfunction after first-line chemotherapy. If the time interval between surgery and first-line chemotherapy was more than 1 year, the risk of renal dysfunction due to chemotherapy decreased (OR=0.54, P=0.196). Eastern Cooperative Oncology Group Performance Status (ECOG PS) Scale≥1 (OR=1.81, P=0.131), anemia before treatment (OR=1.14, P=0.764), the cycles of first-line chemotherapy (OR=1.41, P=0.398) may lead to increase the risk of renal dysfunction, but the differences were not statistically significant. However in the patients who accepted nephrectomy, the risk of renal dysfunction after chemotherapy increased, but the difference was still not statistically significant (OR=3.06, P=0.089). Conclusions: First-line chemotherapy, especially the cisplatin-based regimen, had no significant impact on renal function in the patients with UTUC. Nephrectomy maybe a predictive risk factor for decreased renal function after chemotherapy. Adequate assessment of renal function before treatment, hydration and close monitoring during chemotherapy can effectively protect renal function of the patients.

The natural history and patterns of metastases from mucosal melanoma: an analysis of 706 prospectively-followed patients.

Background: We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would differ from primary mucosal melanomas at different anatomical sites. Patients and methods: Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites. Results: The anatomic sites of the primary mucosal melanomas were from the lower GI tract (26.5%), nasal cavity and paranasal sinuses (23%), gynecological sites (22.5%), oral cavity (15%), urological sites (5%), upper GI tract (5%), and other sites (3.0%). At initial diagnosis, 14.5% were stage I disease, 41% Stage II, 21.5% Stage III, and 23.0% stage IV. Predominant metastatic sites were regional lymph nodes (21.5%), lung (21%), liver (18.5%), and distant nodes (9%). Oral cavity mucosal melanoma had a higher incidence of regional nodal metastases (31.7% versus 19.8%, P = 0.009), and a higher incidence of lung metastases (32.5% versus 18.5%, P = 0.007) compared to other primary mucosal melanomas. There was a 10% incidence of CKIT mutation and 12% BRAF mutation. Mucosal melanomas from nasal pharyngeal and oral, gastrointestinal, gynecological, and urological had a similar survival with a 1-year survival rate (88%, 83%, 86%), 2-year survival rate (66%, 57%, 61%), 5-year survival rate (27%, 16%, 20%), respectively. Conclusions: The largest sample size allows, for the first time, a comparison of primary melanoma stage and patterns of metastases across anatomical sites. With few exceptions, the presenting stages, incidence of nodal and distant metastases, the site of predilection of distant metastases, or overall survival were similar despite different primary anatomic sites. These findings suggest that clinical trials involving mucosal melanomas and the administration of systemic therapy can be applied equally to mucosal melanomas regardless of their primary anatomic site.

BRAF inhibitors: efficacious and tolerable in BRAF-mutant acral and mucosal melanoma.

BRAF inhibitors substantially have impressive clinical efficacy in cutaneous melanoma. However, their role in acral and mucosal melanoma remains unclear. Records were reviewed of patients with metastatic or unresectable BRAF-mutant acral and mucosal melanoma hospitalized and administrated BRAF inhibitors during January 2011 and March 2016. Clinical data were collected to determine PFS, ORR, DCR, OS, and safety. Among 28 acral and 12 mucosal melanoma patients treated with BRAF inhibitors, median PFS were 3.6 (95%CI 3.0-6.4) and 4.4 (95%CI 0.8-12.7) months, median OS were 6.2 (95%CI 6.1-12.1) and 8.2 (95%CI 6.6-19.9) months; ORRs were 38.1% and 20.0%, DCRs were 81.0% and 70.0% in acral and mucosal melanoma, respectively. BRAF inhibitors were well tolerated. The most common adverse effects (AEs) were cutaneous and hematological. Grade 3/4 AEs were relatively rare. In conclusion, BRAF inhibitors have acceptable efficacy and good tolerance in BRAF mutant acral and mucosal melanoma.

[A clinical analysis of 5 patients with infratentorial primary angiitis of central nervous system].

Objective: To explore the clinical characteristics of infratentorial primary angiitis in central nervous system(PACNS). Methods: A total of 5 cases diagnosed as infratentorial PACNS in the neurology department of Navy General Hospital of PLA in 2015 were enrolled in the study. The clinical, imaging and pathological data were collected and analyzed. Results: All the 5 cases were male with the median onset age of thirty-four. Five cases presented with dizziness, two with headache, three with walking unstable, two with facial numbness and one with dysarthria. Rising pressure of cerebrospinal fluid (CSF) (190-245 cmH(2)O, 1 cmH(2)O=0.098 kPa) was found in 4 cases by the lumbar puncture, mildly increased number of leukocyte in 2 cases [(12-28)×10(6)/L], increased CSF protein in 3 cases(540-979 mg/L) and increased IgG index in 3 cases(0.84-1.45). Pons lesions were revealed by magnetic resonance imaging(MRI)in 4 cases, brachium pontis lesions in 2 cases, cerebellum lesions in 2 cases, one with midbrain lesion in 1 case, unilateral lesions in 4 cases and bilateral lesion in 1 case. Different degree of edema and mass effect were shown in all lesions by MRI. Patch like enhancement was found by contrast MRI in 5 cases and meningeal enhancement in 2 cases. Elevation of choline(Cho)peak was found by magnetic resonance spectroscopy(MRS)in 4 cases, reduction of N-acetyl aspartate(NAA) peak in 3 cases, appearance of lactate peak in 1 case and lipid peak in another case. Arterial spin labeling(ASL) was performed in 4 cases and no hyperperfusion was found. Susceptibility weighted imaging(SWI) was performed in 3 cases and microhemorrhage in the lesions was found in 2 cases and normal in 1 case. Magnetic resonance arteriography(MRA) was performed in 1 case and no stenosis was found. Digital subtraction arteriography(DSA) was performed in 1 case and multiple stenosis of the intracranial arteries was showed. Two cases had taken the stereotactic brain biopsy and the histopathologic diagnosis was angiitis. Five cases were treated with methylprednisolone and cyclophosphamide was added on in 1 case. Good prognosis was found in all cases. Conclusions: Infratentorial PACNS mostly attacks middle-aged males. The lesions tend to locate in unilateral pons, brachium pontis, cerebellum and midbrain. Hemorrhage or microhemorrhage in lesions is often found by SWI and no hyperperfusion is shown by ASL, which would be useful to distinguish PACNS from malignant tumors. Given the limitations of brain biopsy in clinical practice, clinical and imaging features would be helpful to diagnose PACNS.

[The correlation factor analysis for conversion of clinically isolated syndrome to multiple sclerosis and neuromyelitis optica].

OBJECTIVE: To analyze the features of patients who converted from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and neuromyelitis optica (NMO) and explore the correlated factors. METHODS: A total of 151 patients admitted in our unit as CIS from January 2009 to December 2014 were enrolled in the study. All patients were divided into the following four groups by locations of the initial lesion, which were the spinal cord, the optic nerve, the brain stem and the multifocal lesions. Data were collected at the baseline including demographics, expanded disability status scale (EDSS) score, site of CIS, presence or absence of cerebrospinal fluid (CSF) oligoclonal bands (OB) and serum aquaporin-4 antibody (AQP4-Ab), evoked potential (EP) and MRI lesions. The conversion rates from CIS to clinically definite MS or NMO were calculated and the correlated factors were explored. RESULTS: With a mean follow-up period of (44.11±17.62)months, 46/151(30.5%) patients converted to MS, 28/151 (18.5%) to definite NMO and 66/151 patients(43.7%)remained as CIS. Other patients were converted to optic neuritis(4/151), one-time transverse myelitis(3/151), acute disseminated encephalomyelitis (1/151) and Balo concentric sclerosis(3/151) . The EDSS score was significantly higher in patients converted to NMO than those converted to MS (P=0.003). The initial manifestation of optic neuritis significantly correlated with the conversion to NMO (P=0.000), while the initial manifestation of CIS with multifocal lesions significantly correlated with the conversion to MS (P=0.000). Neither the isolated BAEP (P=0.703), VEP (P=0.076), SEP (P=0.915) nor the combination of two (P=0.546)or three (P=1.000) of the above parameters could help to distinguish the conversion to MS or NMO. More patients with positive CSF-OB converted to MS (P=0.001), while more patients with positive serum AQP4-Ab converted to NMO (P=0.001). More patients were serum AQP4-Ab positive in those converted to NMO than those converted to MS (P=0.000). Lesions longer than three vertebral segments were dominant in patients converted to NMO (P=0.000). The logistic regression analysis revealed that factors correlated with conversion from CIS to MS were the initial CIS manifestation of multifocal lesions (OR=4.775, P=0.002), positive CSF-OB (OR=7.794, P=0.002) and VEP abnormality (OR=7.251, P=0.001). Factors correlated with conversion from CIS to NMO were female in gender (OR=12.536, P=0.019), positive serum AQP4-Ab (OR=36.410, P=0.002), lesions longer than three vertebral segments (OR=93.602, P=0.001), abnormal VEP and SEP (OR=18.448, P=0.002; OR=12.731, P=0.016). CONCLUSIONS: Factors correlated with the conversion from CIS to MS are initial CIS manifestation of multifocal lesions, positive CSF-OB and abnormal VEP, while those correlated with the conversion from CIS to NMO are female in gender, positive serum AQP4-Ab, initial CIS manifestation with optic nerve, lesions involved more than three vertebral segments and abnormal VEP and SEP.

[Characteristics of sympathetic skin response in patients with multiple system atrophy].

Objective: To provide evidence for early clinical diagnosis of multiple system atrophy(MSA)by studying the characteristics of sympathetic skin responses(SSR) in the patients with MSA. Methods: A total of 47 MSA patients and 32 healthy individuals were enrolled as case group and normal control(NC) group, from in and out patients of Neurology Department of Navy General Hospital from July 2013 to August 2015. SSR was tested by Nicolet electromyography, the latency and abnormal and disappeared rate of SSR were compared. Results: The SSR latency of upper limbs and lower limbs in MSA group had statistical significance compared respectively with the NCgroup (upper limbs: SSR latency was(1 485±187)ms in MSA group, and(1 375±108)ms in NC group, P<0.05; lower limbs: SSR latency was(2 200±386)ms in MSA group, and(1 994±240)ms in NC group, P<0.05). Sex and age had no significant effect on the latency and the abnormal and disappeared rate of SSR in two groups (P>0.05). The upper and lower limb SSR latency in MSA patients with disease duration more than 2 years(SSR latency was (1 592±160)ms in upper limb and (2 268±254)ms in lower limb) were longer than those within 2 years(SSR latency was (1 453±184)ms in upper limb and (2 190±442)ms in lower limb), but only the upper limbs had significantly statistical differences (P<0.05). Both SSR abnormal rate and SSR disappeared rate in MSA patients whose disease duration were more than 2 years(SSR abnormal rate: 85.00%, SSR disappeared rate: 75.00%) were higher than those with shorter disease duration(SSR abnormal rate: 55.56%, SSR disappeared rate: 22.22%), and both were statistically significant (SSR abnormal rate: P<0.05, SSR disappeared rate: P<0.001). The upper and lower limb SSR latency of MSA-C subgroup had no statistical difference compared with MSA-P subgroup(P>0.05). The SSR abnormal rate in MSA-C subgroup(78.13%) was higher than that of MSA-P subgroup(46.76%), and were statistically significant (P<0.05). The SSR disappeared rate in MSA-C subgroup has no statistical difference compared with the MSA-P subgroup(P>0.05). Conclusions: SSR is helpful to diagnose MSA. The latency and the abnormal and disappeared rate of SSR are significantly increased with the extension of MSA duration. The SSR abnormal rate in MSA-C patients is higher than that in MSA-P patients, and symmetrically abnormal SSR is more supporting the diagnosis of MSA.

[Efficacy and the multivariate analysis of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma].

Objective: To investigate the efficacy and the influence factors of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma (mRCC). Methods: Clinical data of mRCC patients with sunitinib administered as the first line treatment from August 2008 to December 2015 were retrospectively reviewed. The efficacy and the influence factors of sunitinib treatment was analyzed using the Kaplan-Meier method and Cox proportional hazards models. Results: In all 166 patients who received sunitinib as first-line treatment, objective response rate was 31.9%, disease control rate was 84.3%. The median progression free survival (PFS) and overall survival (OS) were 11.0 months (95% CI: 9.0-14.0) and 28.0 months (95% CI: 19.0-33.0), respectively. Multivariate analysis showed that pathological types (clear cell carcinoma vs non clear cell carcinoma, HR: 1.889 vs 2.353), time from diagnosis to treatment(<1 year vs ≥1 year, HR: 0.293 vs 0.322) and the number of metastatic sites (1 vs ≥1, HR: 2.360 vs 4.351) were the independent prognostic factors for PFS and OS (P<0.05). Conclusions: The efficacy of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma is similar to reports at home and abroad. The patients with renal clear cell carcinoma, time from diagnosis to treatment> 1 year, and only one metastatic site would get better PFS and OS.

[Clinical analysis of 9 children with refractory N-methyl-D-aspartate receptor antibody encephalitis children treated with tocilizumab].

Objective: To analyze the clinical features of children with refractory N-methyl-D-aspartate (NMDA) receptor antibody encephalitis treated with tocilizumab. Methods: Demographic and clinical manifeatations, immunotherapy and prognosis data of 9 children with refractory NMDA receptor antibody encephalitis who received tocilizumab in the Department of Pediatrics Neurology, XiangYa Hospital of Central South University from August 2021 to September 2023 were collected retrospectively. Prognosis was evaluated using the modified Rankin scale at initial diagnosis, at the initiation of tocilizumab treatment, and at the last follow-up. Treatment related complications, neuroimaging, and electroencephalography data were analyzed. Results: Among the 9 children, 6 were male and 3 were female, with an onset age of 4.2 (2.8, 8.7) years. At the onset of the disease, 9 children had a modified Rankin scale score of 5. When tocilizumab treatment was initiated, 7 children had a score of 5, and 2 children had a score of 4. The interval between the onset and initiation of tocilizumab treatment was 12 (5, 27) months, and the treatment frequency was 8 (5, 13) times. The follow-up time was 2.8 (1.5, 3.7) years. At the last follow-up, the symptoms of 9 children, including movement disorder, sleep disorder, consciousness disorder, silence and autonomic dysfunction, were improved to varying degrees, and none of them had seizures. At the last follow-up, 4 cases with a modified Rankin scale score of 0, 1 case with a score of 1, 2 cases with a score of 3, 1 case with a score of 4 and 1 case with a score of 5. The modified Rankin scale at the last follow-up was significantly different from that at the start of tocilizumab (Z=-2.56, P=0.014). All children had no serious adverse reactions during the treatment. Conclusions: After treatment with tocilizumab, the symptoms in patients with refractory NMDA receptor antibody encephalitis, including movement disorder, sleep disorder, consciousness disorder, silence and autonomic dysfunction were improved, and none of them had seizures. The modified Rankin scale were improved, and the safety was good.

[A preliminary study of the treatment of chronic tinnitus in menopausal women].

Objective:To explore the hormone treatment outcome of the menopause related tinnitus.Method:From April 2016 to October 2016, Fifty-nine patients who were diagnosed with menopausal syndrome in the menopause clinics of Beijing Shijitan Hospital were enrolled in our study, and questionnaire-based investigation about tinnitus and menopause was performed. According to the patients' intention, they were divided into treatment group and control group. Age, BMI, menopausal KMI scores, severity of tinnitus were statistically analyzed. After 3 months follow up, the different therapeutic effects of tinnitus between two groups were analyzed. Result:There was no significant difference between two groups in age, BMI, menopausal KMI scores and severity of tinnitus. The tinnitus in untreated patients after 3 months follow up showed no improvement, while 5 cases had been cured in treatment group. Conclusion:Menopause related tinnitus was an independent type of tinnitus. Menopausal hormone therapy can be applied for treatment after excluding other tinnitus risk factors.