Ductal Lavage for Patients With Nonlactational Mastitis: A Single-Arm, Proof-of-Concept Trial.

BACKGROUND: Surgery, steroids, and/or observations alone have been proposed for patients with nonlactational mastitis (NLM), but most of these studies were retrospective. The optimal treatment for these patients remains unclear. This prospective, single-arm, proof-of-concept trial aimed to evaluate the feasibility and safety of ductal lavage as a novel treatment for patients with NLM. METHODS: Eligible patients with NLM received an intraductal infusion of corticosteroids and antimicrobial agents and returned the next day for a breast massage. This cycle was repeated for 2 wk, and we followed up these patients for 1 y. Patients did not receive surgery or steroids after ductal lavage. The primary endpoint was the time to complete response (CR). RESULTS: This trial included 32 patients with a median (range) age of 32 (20-53). Skin erythema and tenderness were the major symptoms. The median (range) visual analog score was 5 (0-9). There were 21 (65.6%), 4 (12.5%), and 7 (21.9%) patients diagnosed as idiopathic granulomatous mastitis, periductal mastitis, and unspecific NLM, respectively. During the ductal lavage, the median (range) number of cannulated ducts at first attempt was 5 (3-8). Ductal lavage significantly reduced the visual analog score and mastitis score (M-score) (P < 0.01). Within a median follow-up of 15.6 mo, 93.8% (30/32) of patients achieved CR. The median (range) time to CR was 6 (0.5-21) mo. Three patients (10.0%) relapsed. No adverse events associated with ductal lavage were observed. CONCLUSIONS: Ductal lavage for patients with NLM is feasible and safe, and a definitive randomized controlled trial for further investigation is warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02794688.

Explicit hypoxia targeting with tumor suppression by creating an "obligate" anaerobic Salmonella Typhimurium strain.

Using bacteria as therapeutic agents against solid tumors is emerging as an area of great potential in the treatment of cancer. Obligate and facultative anaerobic bacteria have been shown to infiltrate the hypoxic regions of solid tumors, thereby reducing their growth rate or causing regression. However, a major challenge for bacterial therapy of cancer with facultative anaerobes is avoiding damage to normal tissues. Consequently the virulence of bacteria must be adequately attenuated for therapeutic use. By placing an essential gene under a hypoxia conditioned promoter, SalmonellaTyphimurium strain SL7207 was engineered to survive only in anaerobic conditions (strain YB1) without otherwise affecting its functions. In breast tumor bearing nude mice, YB1 grew within the tumor, retarding its growth, while being rapidly eliminated from normal tissues. YB1 provides a safe bacterial vector for anti-tumor therapies without compromising the other functions or tumor fitness of the bacterium as attenuation methods normally do.

Assessing second echelon lymph nodes during sentinel lymph node biopsy: can we have more accurate axillary treatment for breast cancer patients?

Sentinel lymph node biopsy (SLNB) is the standard treatment for breast cancer patients with clinically negative axilla. For patients with positive sentinel lymph nodes, axillary lymph node dissection (ALND) was required. However, approximately a half of the SLNs-positive patients were found to have clear axillary lymph nodes after ALND, indicating that they had received unnecessary ALND without therapeutic benefit. Therefore, we propose a hypothesis for solution of this clinical problem. We defined the second echelon lymph nodes (SELNs) as those nodes receiving lymphatic drainage directly from the SLNs. For patients with positive-SLNs, SELNs can be biopsy and assessed. If SELNs are negative, no more ALND was needed in these patients even if their SLNs are positive. If our hypothesis were confirmed to be true, we can tailored our axillary treatment to more breast cancer patients, avoiding unnecessary ALND and its complications.

Lentiviral delivery of short hairpin RNAs protects CD4 T cells from multiple clades and primary isolates of HIV.

Viral heterogeneity is a major hurdle for potential therapeutic use of RNA interference (RNAi) against HIV-1. To determine the extent of RNAi tolerance to mutations, we tested 3 viral target sites with differing propensity for mutations: a highly variable rev sequence, a gag sequence conserved only among clade B isolates, and a vif sequence highly conserved across clades. Lentiviral expression of all 3 shRNAs inhibited replication of the homologous HIV(IIIB) strain. However, they differed in their ability to protect primary CD4 T cells against multiple isolates within and across HIV clades. The least conserved rev sequence inhibited only 2 of 5 clade B isolates. The gag sequence (conserved within clade B) protected 5 of 5 clade B isolates but not other clade viruses with 2 or 3 mutations in the central region. In contrast, the vif sequence, which was conserved across clades except for single mutations at positions 14 and 17, inhibited viruses from 5 different clades. Moreover, siRNAs with introduced mutations at sites of gag sequence polymorphisms showed reduced antiviral activity, whereas mutations in vif siRNA only modestly decreased silencing. Thus, although 1 or 2 mutations at peripheral sites are tolerated, mutations in the central target cleavage region abolish RNAi activity.