Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆.

BACKGROUND: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/µl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. RESULTS: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%). CONCLUSIONS: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.

[A multicenter, randomized, open and positive parallel controlled clinical study of clotrimazole vaginal expansion suppository and vaginal tablet in the treatment of mild and moderate vulvovaginal candidiasis].

Objective: Using clotrimazole vaginal tablet as a positive control, to evaluate the results of clotrimazole vaginal expansion suppository in the treatment of mild and moderate vulvovaginal candidiasis in terms of efficacy, patient satisfaction, side effects, and recurrence rate. Methods: This study was jointly conducted by 5 hospitals from August 2017 to October 2018, patients with mild and moderate vulvovaginal candidiasis confirmed by fungal culture and symptoms scores were selected. They were randomized to experimental group and control group as 1∶1 ratio. In the experimental group (n=105), the subjects applied clotrimazole vaginal expansion suppository (150 mg) daily at night for 7 days. In the control group (n=106), the subjects used a single dose of clotrimazole vaginal tablet (500 mg). Follow-ups were performed at (8±3) and (30±5) days after the discontinuation of the drugs, respectively. The difference in clinical symptoms and signs scores was used to evaluate the improvement of clinical symptoms, and the patient's satisfaction and side effects were recorded. Results: At the first follow-up, the experimental group and control group were followed up by fungal culture on the cure rate [66.7% (70/105) versus 63.2% (67/106), P>0.05] and total effective rate [98.1% (103/105) versus 99.1% (105/106), P>0.05], the differences were not statistically significant. At the second follow-up, the recurrence rates of the experimental group and the control group were 5.7% (4/70) and 14.9% (10/67), respectively, with no significant difference (P>0.05). In the evaluation of patient satisfaction, the leakage of the drug in the experimental group was significantly better than that in the control group (P<0.01). The side effects mainly included vaginal stimulation, itching and burning sensation, and there was no statistical difference between the two groups (χ2=1.070, P=0.586). Conclusions: In the treatment of mild and moderate vulvovaginal candidiasis, clotrimazole vaginal expansion suppository is no less effective than clotrimazole vaginal tablet, and there is no significant difference in the recurrence rate between the two. In terms of patient satisfaction, clotrimazole vaginal expansion suppository is superior to clotrimazole vaginal tablet.

Clinical-Morphological Aspects in Spinal Tuberculosis.

Osteoarticular tuberculosis (OATB) Aim: The authors made a clinical morphological assessment of tissue samples from patients admitted in Surgical Departments of the Emergency County Hospital of Craiova, Romania, between 1990 and 2015, proved as presenting tuberculous lesions of the spine in the Department of Pathology of the same Hospital. MATERIALS AND METHODS: The studied material consisted of bone, joint and sometimes muscle tissue fragments resulted from biopsies or surgical excisions from 7 cases coming out of 54 patients investigated in the above-mentioned period of time, where the established histological diagnosis was tuberculosis (TB). For diagnostic confirmation, Ziehl-Neelsen staining has been used as a rule but, in some cases, immunohistochemistry was also used. RESULTS: TB lesions have prevailed in men and around the age of 50 years. Thoracic segment of the spine was the most involved. Epithelioid and giant Langhans cells dominated the inflammatory cellular population. Necrosis was always present, usually in its classical acidophilic form. Fibrosis was almost always absent. On the whole, the granulomatous reaction was in almost half of the cases hyporeactive and disorganized. CONCLUSIONS: The clinical morphological profile of our series is fitting with data described in the literature. Because of its life threatening potential, spinal TB should be investigated thoroughly especially in its morphological features in order to obtain as quickly as possible an etiological diagnosis.

Osteoraticular Tuberculosis-Brief Review of Clinical Morphological and Therapeutic Profiles.

Osteoarticular tuberculosis (OATB) is a rare form of tuberculosis (TB) whose incidence rose significantly nowadays especially in the underdeveloped countries. The main risk factors predisposing to this new challenge for the medical system are the Human Immunodeficiency Virus (HIV) epidemic, the migration from TB endemic areas and the development of drug and multidrug-resistant strains of Mycobacterium tuberculosis (Mt). The disease affects both genders and any age group although the distribution depending on gender is controversial and that depending on age has a bimodal pattern. In most cases the initial focus is elsewhere in the organism and the most frequent pathway of dissemination is lympho-haematogenous. The clinical picture includes local symptoms as pain, tenderness and limitation of motion, with some particularities depending on the segment of the osteoarticular system involved, sometimes accompanying systemic symptoms specific for TB and other specific clinical signs as cold abscesses and sinuses. The radiographic features are not specific, CT demonstrates abnormalities earlier than plain radiography and MRI is superior to plain radiographs in showing the extent of extraskeletal involvement. Both CT and MRI can be used in patient follow-up to evaluate responses to therapy. TBhas been reported in all bones of the body, the various sites including the spine (most often involved) and extraspinal sites (arthritis, osteomyelitis and tenosynovitis and bursitis). Two basic types of disease patterns could be present: the granular type (most often in adults) and the caseous exudative type (most often in children) one of which being predominant. The algorithm of diagnosis includes several steps of which detection of Mt is the gold standard. The actual treatment is primarily medical, consisting of antituberculosis chemotherapy (ATT), surgical interventions being warranted only for selected cases. It is essential that clinicians know and refresh their knowledge about manifestations of OATB.

[Relationship of HPV infection and BV, VVC, TV: a clinical study based on 1 261 cases of gynecologic outpatients].

Objective: To Explore the relationship between HPV infection and bacterial vaginosis(BV), vulvovaginal candidiasis(VVC), and trichomonal vaginitis(TV). Methods: Clinical data from 1 261 gynecologic outpatients who underwent the vaginal microecology and HPV type detection during June 2015 to December 2015 were collected and analyzed in the First Affiliated Hospital of Xi'an Jiaotong University. Results: In 1 261 patients, 328 cases infected with HPV, infection rate was 26.01%(328/1 261); vaginal infectious disease in 328 cases of HPV infections were 219 cases(66.8%, 219/328), vaginal infectious diseases in 933 cases of HPV uninfected were 503 cases(53.9%, 503/933), incidence of vaginal infectious disease in HPV infected patients was higher than that in HPV uninfected patients(χ2=5.87, P=0.01). 142 cases of BV had 54 cases infected with HPV(38.0%, 54/142), 296 cases of intermediate type BV had 88 cases infected with HPV(29.7%, 88/296), 231 cases of normal vaginal microecology had 51 cases infected with HPV(22.1%, 51/231), 99 cases of VVC had 15 cases infected with HPV(15.2%, 15/99), 2 patients with TV had 0 cases infected with HPV(0/2), HPV infection rate in BV, intermediate type BV patients were significantly higher than normal patients(P<0.05), while there were no statistical differences among VVC, TV and normal patients(P>0.05). The intensity of HPV infection were positively correlated with BV, intermediate type BV(OR=2.17, 95% CI: 1.37-3.43, P<0.01; OR=1.49, 95% CI: 1.00-2.22, P= 0.04); while, VVC, TV were uncorrelated with HPV infection(all P>0.05). Conclusions: BV, intermediate type BV are positively correlated with HPV infection, especially for the high-risk HPV. VVC and TV are not correlated with HPV infection.

Combination chemotherapy for high-risk gestational trophoblastic tumour.

BACKGROUND: Gestational trophoblastic disease (GTD) includes gestational trophoblastic tumour and hydatidiform mole. Many women of reproductive age are affected by this disease although its incidence differs by geographical location. A number of chemotherapy regimens are used for treating the disease, such as methotrexate, actinomycin D and cyclophosphamide (MAC), methotrexate, actinomycin D, cyclophosphamide, doxorubicin, melphalan, hydroxyurea and vincristine (CHAMOC), etoposide, methotrexate and actinomycin (EMA) plus cyclophosphamide and vincristine (CO) (EMA-CO), etoposide, methotrexate and actinomycin (EMA) plus etoposide and cisplatin(EP) (EMA-EP). The efficacy of these drugs has not been systematically reviewed. OBJECTIVES: To determine the efficacy and safety of combination chemotherapy in treating high-risk GTT. SEARCH STRATEGY: Electronic searches of MEDLINE, EMB, Cochrane Central Register of Controlled Trials (CENTRAL) and CBM were carried out. Four journals were handsearched and other searching methods were used for identifying more studies. SELECTION CRITERIA: The review included randomized controlled trials (RCTs) or quasi-RCTs of combination chemotherapy for treating high-risk GTT. Patients with placental-site trophoblastic tumour (PSTT), who had received chemotherapy in the previous two weeks, or patients with chemotherapy intolerance were excluded. DATA COLLECTION AND ANALYSIS: Two investigators independently collected data using a data extraction form. Meta-analysis was not performed and the review was conducted as a narrative review. MAIN RESULTS: One study with 42 participants was included in this review. It indicated that a MAC regimen was better than a CHAMOCA regimen for high-risk GTT because of lower toxicity. The quality of the study was unclear. AUTHORS' CONCLUSIONS: The methodological limitations of the included study prevent any firm conclusions about the best combination chemotherapy regimen for high-risk GTT. High quality studies are required.