Treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: the role of corticosteroids

We aimed to evaluate the treatments, particularly the role of corticosteroids, in patients with late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). One hundred and sixty-three consecutive patients who underwent non-T-cell-depleted allo-HSCT and met the criterion of LOHC after allo-HSCT were enrolled in this study. The median time from allo-HSCT to the occurrence of LOHC was 29 (range, 4–155) days. Pathogens identified in blood and/or urine samples from 143 patients were mostly viruses. All of the patients with LOHC received intravenous fluid hydration, alkalization, and forced diuresis, of which 2 patients achieved complete remission (CR) after these treatments. The remaining 161 patients received anti-infection therapies and 71 achieved CR after the therapies. Corticosteroids were additionally applied to 83 out of 90 patients who did not achieve CR after anti-infection therapies, and 88.0% (n?=?73) of them showed a grade 3 to 4 LOHC at the beginning of corticosteroid therapy. Thirty-five patients showed an immediate response (CR or downgraded at least one grade) within 1 week after the beginning of the corticosteroid therapy. Sixty-four patients (77.1%) achieved CR after corticosteroid therapy, and the median period from the beginning of corticosteroid therapy to CR was 17 days. Thus, we observed that viruses were the most common pathogens in LOHC after allo-HSCT and that anti-infection therapies were critical. For patients not showing a satisfactory response to anti-infection therapies, additional corticosteroid therapy may help to achieve CR.     

Sofosbuvir plus ribavirin with or without peginterferon for the treatment of hepatitis C virus: Results from a phase 3b study in China

Background and Aim

Sofosbuvir is a nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B RNA polymerase with pangenotypic potency. This phase 3b study evaluated the safety and efficacy of sofosbuvir + ribavirin ± peginterferon in Chinese patients infected with HCV genotype 1, 2, 3, or 6.

Methods

Patients with genotype 1 or 6 received sofosbuvir + peginterferon/ribavirin for 12 weeks or sofosbuvir + ribavirin for 24 weeks, depending on prior treatment and interferon eligibility. Patients with genotype 2 or 3 received sofosbuvir + ribavirin for 12 or 24 weeks, respectively. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR12).

Results

Of 389 patients, 42% had genotype 1, 16% genotype 2, 32% genotype 3, and 9% genotype 6. Half were male, 58% were treatment‐naïve, and 15% had cirrhosis. SVR12 rates for patients receiving 12 weeks of sofosbuvir + peginterferon/ribavirin were 94% (95% confidence interval [CI], 87–98%) for HCV genotype 1 and 97% (95% CI, 84–100%) for genotype 6. SVR12 rates for those receiving sofosbuvir + ribavirin for 24 weeks were 95% (95% CI, 87–99%) for genotype 1, 100% (95% CI, 40–100%) for genotype 6, and 95% (95% CI, 90–98%) for genotype 3. For genotype 2 patients receiving sofosbuvir + ribavirin for 12 weeks, the SVR12 rate was 92% (95% CI, 83–97%). Twenty patients (5%) relapsed. Ten (3%) experienced serious adverse events. Three (< 1%) discontinued treatment because of adverse events, of whom one died because of treatment‐unrelated adverse events.

Conclusions

Sofosbuvir‐based regimens were highly effective and safe in Chinese patients with HCV genotype 1, 2, 3, or 6, suggesting sofosbuvir could serve as the backbone for HCV treatment in China irrespective of genotype.     

中华按蚊细胞色素P450基因表达特征分析

目的 探讨6种溴氰菊酯抗性候选细胞色素P450（CYP）基因（CYP6M3、CYP6Y1、CYP6P5、CYP4H14、CYP4G17、CYP12F16）在中华按蚊体内的表达特征。方法 收集中华按蚊不同发育时期（卵、幼虫、蛹、雌性成蚊和雄性成蚊）和组织（唾液腺、马氏管、中肠、卵巢以及脂肪体）样本,以及雌性成蚊在暴露于不同溴氰菊酯剂量（0、1.25、3.75、6.25、12.5 μg/瓶）和时间（0,5、15、30、60 min）后的样本.提取总RNA,利用反转录实时定量PCR（qPCR）技术分析CYP6M3、CYP6Y1、CYP6P5、CYP4H14、CYP4G17、CYP12F16基因在中华按蚊不同发育时期、组织以及不同溴氰菊酯接触剂量和时间下的相对表达量。结果 CYP6M3与CYP6Y1基因在雄性中华按蚊成蚊体内的表达量最高,CYP6M3基因在雄性成蚊体内的表达量是雌性成蚊的35.1倍,CYP6Y1基因在雄性成蚊体内的表达量是雌性成蚊的61.4倍;CYP4H14基因在幼虫期表达量最低,且在雌性成蚊体内表达量是四龄幼虫体内表达量的22.5倍。候选CYP基因在中华按蚊不同组织内的表达量差异具有统计学意义,CYP6M3基因在马氏管内的表达量是在卵巢中的38.9倍,CYP6Y1基因在脂肪体内的表达量是在卵巢中的9.1倍,CYP6P5基因在中肠内的表达量是在卵巢中的30.3倍,CYP4G17基因在脂肪体内的表达量是在卵巢中的4.6倍,CYP12F16基因在马氏管内的表达量是在卵巢中的4.4倍。接触不同溴氰菊酯剂量和时间对候选CYP基因的表达水平表现出一定的诱导效应,影响候选CYP基因在中华按蚊体内的表达。结论 候选CYP基因在不同发育期中华按蚊体内和不同组织中差异表达,暴露于不同溴氰菊酯剂量和时间影响CYP基因在中华按蚊体内表达。     

ALPPS治疗巨大原发性肝癌患者近远期疗效研究

目的 探讨联合肝脏分隔和门静脉结扎的二步肝切除术(ALPPS)治疗巨大原发性肝癌(PLC)患者的近远期疗效.方法 2016年1月～2018年2月我院诊治的98例巨大PLC患者,其中20例接受ALPPS治疗(A组),38例在经肝动脉化疗栓塞术(TACE)治疗后手术切除肿瘤(B组),和40例接受直接手术切除肿瘤(C组).术...     

异丙肾上腺素预处理对大鼠胰腺移植后缺血再灌注损伤的抑制作用

目的:探讨减轻大鼠胰腺移植后缺血再灌注损伤的保护作用机制.方法:IPC后动态检测大鼠胰腺组织热休克蛋白表达.建立大鼠胰腺移植缺血再灌注模型,选择表达热休克蛋白高峰时段供体大鼠胰腺移植作为实验组,未预处理供体大鼠胰腺移植作为对照组.移植后6 h,采集静脉血及移植胰腺.热休克蛋白70(HSP70)分别用Western blot法及免疫组织化学法检测.免疫组织化学法测定肿瘤坏死因子-α(TNF-α)表达.流式细胞仪检测胰腺细胞凋亡率.碘淀粉比色法检测血淀粉酶水平.结果:IPC后供体大鼠胰腺中HSP70的表达在24 h达到高峰,与其他各时段比较具有显著差异(0.92±0.25 vs 0.24±0.04,0.34±0.06,0.58±0.07,0.62±0.11,0.25±0.09,均P<0.05),IPC后6 h,12 h,24 h,36 h大鼠胰腺中HSP70的表达与未预处理组相应时段比较差异也显著(0.34±0.06 vs 0.28±0.07,0.58±0.07 vs 0.25±0.04.0.92±0.25 vs 0.27±0.05,0.62±0.11vs 0.25±0.06,均P<0.05),48 h恢复到原来水平.而未预处理组各时段间比较差异无统计学意义(P>0.05).HSP70主要表达于胰腺腺泡细胞及血管壁.对照组胰腺组织中TNF-α、细胞凋亡率、中性粒细胞、血淀粉酶的水平明显升高,与假手术组相比差异显著(均P<0.01).实验组降低了胰腺组织中TNF-α、细胞凋亡率、白细胞数、血淀粉酶的水平,与对照组比较差异具有统计学意义(11 929±1220vs46 111±3127,26.7%±4.5%vs 37.4%±4.7%,3 308±531 vs 6668±1506,1057 IU/L±148IU/L vs 1 408 IU/L±195IU/L,均P<0.05).结论:IPC减轻了大鼠胰腺移植后缺血再灌注损伤,IPC保护作用与HSP70的诱导生成有关.     

Primary pulmonary lymphoepithelioma-like carcinoma: A case report of pathological complete response (pCR) by neoadjuvant treatment

Rationale:Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of non-small cell lung cancer (NSCLC). It is predominantly reported in East Asia and currently there is no standard treatment for this disease. We report a case of stage IV PPLELC that achieved pathological complete response (pCR) by neoadjuvant treatment.Patient concerns:The patient was a 46-year-old male who developed hemoptysis for about 20 ml of volume accompanied by cough and sputum after physical labor.Diagnoses:Contrast enhanced chest CT scanning showed occupation of left lower hilar area and left pleural effusion. Combined with medical history and auxiliary examination, the patient was formally diagnosed stage IV lymphoepithelioma-like carcinoma of the left lower lung (T3N0M1a pleura).Interventions:The patient was given Sintilimab combined with gemcitabine + nedaplatin chemotherapy (GP) regimen for four cycles with 3 weeks as a cycle, supplemented with antiemetics and stomach protection drugs to reduce chemotherapy-related side effects.Outcomes:After 4 cycles of treatment, the patient''s left lung lesion has been markedly reduced and the left pleural effusion has also been significantly absorbed. Remarkably, surgical biopsies found no cancer cells in the lesion site and postoperative pathology showed complete pathological remission (pCR).Lessons:We reported a case of PPLELC that is sensitive to neoadjuvant treatment, showing excellent effectiveness and safety and achieving pCR.     

Natural killer cells in hepatitis C:Current progress

Patients infected with the hepatitis C virus(HCV) are characterized by a high incidence of chronic infection, which results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The functional impairment of HCV-specific T cells is associated with the evolution of an acute infection to chronic hepatitis. While T cells are the important effector cells in adaptive immunity, natural killer(NK) cells are the critical effector cells in innate immunity to virus infections. The findings of recent studies on NK cells in hepatitis C suggest that NK cell responses are indeed important in each phase of HCV infection. In the early phase, NK cells are involved in protective immunity to HCV. The immune evasion strategies used by HCV may target NK cells and might contribute to the progression to chronic hepatitis C. NK cells may control HCV replication and modulate hepatic fibrosis in the chronic phase. Further investigations are, however, needed, because a considerable number of studies observed functional impairment of NK cells in chronic HCV infection. Interestingly, the enhanced NK cell responses during interferon-α-based therapy of chronic hepatitis C indicate successful treatment. In spite of the advances in research on NK cells in hepatitis C, establishment of more physiological HCV infection model systems is needed to settle unsolved controversies over the role and functional status of NK cells in HCV infection.     

National level data analysis of facial lacerations in Korea using the National Health Insurance Service (NHIS) database

No national epidemiological investigations have been conducted recently regarding facial lacerations. The study was performed using the data of 3,634,229 people during the 5-year period from 2014 to 2018 archived by the National Health Information Database (NHID) of the Health Insurance Review and Assessment Service. Preschool and children under 10 years old accounted for about one-third of patients. Facial lacerations were concentrated in the “T-shaped” area, which comprised forehead, nose, lips, and the perioral area. The male to female ratio for all study subjects was 2.16:1. Age and gender are significantly related with each other (P < .001). Mean hospital stays decreased, and numbers of outpatient department visits per patient were highest for hospitals and lowest for health agencies. Over the study period, hospital costs per patient in tertiary and general hospitals increased gradually. Preschool and school-aged children are vulnerable to trauma. Male patients outnumbered female patients by a factor of more than 2. The “T-shaped’” area around forehead is vulnerable to injury. Total cost of medical care benefits per patient in tertiary hospitals was about 7 times on average than in health agencies. Regarding functional, behavioral, and aesthetic outcomes, more attention should be paid to epidemiologic data and hospital costs for facial lacerations.     

Changes of quantitative CT-based airway wall dimensions in patients with COVID-19 during early recovery

BackgroundAs the coronavirus disease 19 (COVID-19) pandemic evolves, the need for recognizing the structural pulmonary changes of the disease during early convalescence has emerged. Most studies focus on parenchymal destruction of the disease; but little is known about whether the disease affects the airway. This study was conducted to investigate the changes in airway dimensions and explore the associated factors during early convalescence in patients with COVID-19.MethodsWe retrospectively analyzed quantitative computed tomography (CT)-based airway measures of 69 patients with COVID-19 from 5 February to 17 March 2020, and 32 non-COVID-19 participants from 1 January 2018 to 31 December 2019 from Guangzhou, China. The well-established measures of wall area fraction and the square root of the wall area of a hypothetical bronchus with an inner perimeter of 10 mm, were used to describe airway wall dimensions. We described the characteristics of the dimensions and inner area of airways in 66 patients with COVID-19 at the initial and convalescent stages of the disease, and compared them with the non-COVID-19 group. Linear regression models were constructed to investigate the association of airway dimensions with duration of hospitalization or disease severity after recovery. Partial correlation coefficients were calculated to investigate whether inflammatory markers were related to airway dimensions.ResultsAmong 66 patients with COVID-19, airway dimensions were greater during disease initiation than early convalescence, which was significantly greater than in non-COVID-19 participants. No significant difference was found between the patients with COVID-19 at the initial stage and the non-COVID-19 controls regarding the first to eighth generations of the inner area. In adjusted regression models, duration of hospitalization was negatively associated with wall area fraction of the first to the sixth generation of airways. No significant associations exist between airway dimensions and disease severity, or airway dimensions with inflammatory markers.ConclusionsAirway dimensions in patients with COVID-19 during disease initiation are greater than those in non-COVID-19 participants. Such structural airway changes continue to remain significantly greater during early convalescence. No evidence shows that disease severity or inflammatory markers are associated with airway dimensions, implying that the primary lesion attacked by COVID-19 might not be the airways.