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Sarcina species are anaerobic gram-positive cocci rarely seen in the upper gastrointestinal tract and associated with delayed gastric emptying. We present 3 cases of Sarcina infection with varying clinical presentations including the first reported case of Sarcina in a patient with eosinophilic esophagitis. Although the pathogenesis of Sarcina is unclear, awareness of the bacteria is important as they can usually only be detected on histopathologic examination of upper gastrointestinal biopsies. Treatment in symptomatic patients may prevent severe complications such as emphysematous gastritis and gastric perforation. [ABSTRACT FROM AUTHOR]

HER2-directed therapies are less effective in patients with ERposcompared to ERnegbreast cancer, possibly reflecting bidirectional activation between HER2 and estrogen signaling pathways. We investigated dual blockade using anti-HER2 vaccination and anti-estrogen therapy in HER2pos/ERposearly breast cancer patients. In pre-clinical studies of HER2posbreast cancer cell lines, ERposcells were partially resistant to CD4+Th1 cytokine-induced metabolic suppression compared with ERnegcells. The addition of anti-estrogen treatment significantly enhanced cytokine sensitivity in ERpos, but not ERneg, cell lines. In two pooled phase-I clinical trials, patients with HER2posearly breast cancer were treated with neoadjuvant anti-HER2 dendritic cell vaccination; HER2pos/ERpospatients were treated with or without concurrent anti-estrogen therapy. The anti-HER2 Th1 immune response measured in the peripheral blood significantly increased following vaccination, but was similar across the three treatment groups (ERnegvaccination alone, ERposvaccination alone, ERposvaccination + anti-estrogen therapy). In the sentinel lymph nodes, however, the anti-HER2 Th1 immune response was significantly higher in ERpospatients treated with combination anti-HER2 vaccination plus anti-estrogen therapy compared to those treated with anti-HER2 vaccination alone. Similar rates of pathologic complete response (pCR) were observed in vaccinated ERnegpatients and vaccinated ERpospatients treated with concurrent anti-estrogen therapy (31.4% vs. 28.6%); both were significantly higher than the pCR rate in vaccinated ERpospatients who did not receive anti-estrogen therapy (4.0%,p= 0.03). Since pCR portends long-term favorable outcomes, these results support additional clinical investigations using HER2-directed vaccines in combination with anti-estrogen treatments for ERpos/HER2posDCIS and invasive breast cancer. [ABSTRACT FROM PUBLISHER]

Mitral valve translocation (MVT) is a novel procedure that was developed to treat patients with severe, symptomatic, secondary mitral regurgitation (MR). MVT enhances leaflet coaptation by insertion of an autologous pericardial patch interposed between the mitral annulus and the native mitral leaflets. The patch substantially increases total leaflet surface area and creates supranormal coaptation. In addition, it relieves leaflet tethering by transposing the native valve deeper into the ventricle and decreases the circumference of the annulus. The enhanced coaptation produced by MVT may protect against recurrent MR in patients with continued adverse left ventricular remodeling. The procedural steps include detachment of the intact native mitral valve at the annulus, placement of interrupted pledgeted sutures around the annulus to secure the proximal aspect of the patch, and attachment of the native valve to the distal aspect of the patch using running suture. Follow-up of patients who have undergoing MVT is ongoing, with satisfactory short-term results, including sustained MR grades of ≤mild and 14 mm coaptation at 12 months.

HER2-directed therapies are less effective in patients with ER pos compared to ER neg breast cancer, possibly reflecting bidirectional activation between HER2 and estrogen signaling pathways. We investigated dual blockade using anti-HER2 vaccination and anti-estrogen therapy in HER2 pos /ER pos early breast cancer patients. In pre-clinical studies of HER2 pos breast cancer cell lines, ER pos cells were partially resistant to CD4 + Th1 cytokine-induced metabolic suppression compared with ER neg cells. The addition of anti-estrogen treatment significantly enhanced cytokine sensitivity in ER pos , but not ER neg , cell lines. In two pooled phase-I clinical trials, patients with HER2 pos early breast cancer were treated with neoadjuvant anti-HER2 dendritic cell vaccination; HER2 pos /ER pos patients were treated with or without concurrent anti-estrogen therapy. The anti-HER2 Th1 immune response measured in the peripheral blood significantly increased following vaccination, but was similar across the three treatment groups (ER neg vaccination alone, ER pos vaccination alone, ER pos vaccination + anti-estrogen therapy). In the sentinel lymph nodes, however, the anti-HER2 Th1 immune response was significantly higher in ER pos patients treated with combination anti-HER2 vaccination plus anti-estrogen therapy compared to those treated with anti-HER2 vaccination alone. Similar rates of pathologic complete response (pCR) were observed in vaccinated ER neg patients and vaccinated ER pos patients treated with concurrent anti-estrogen therapy (31.4% vs. 28.6%); both were significantly higher than the pCR rate in vaccinated ER pos patients who did not receive anti-estrogen therapy (4.0%, p = 0.03). Since pCR portends long-term favorable outcomes, these results support additional clinical investigations using HER2-directed vaccines in combination with anti-estrogen treatments for ER pos /HER2 pos DCIS and invasive breast cancer.

A decade since the availability of Mycobacterium tuberculosis (Mtb) genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates. Towards this, we synergized crowd sourcing and social networking methods through an initiative 'Connect to Decode' (C2D) to generate the first and largest manually curated interactome of Mtb termed 'interactome pathway' (IPW), encompassing a total of 1434 proteins connected through 2575 functional relationships. Interactions leading to gene regulation, signal transduction, metabolism, structural complex formation have been catalogued. In the process, we have functionally annotated 87% of the Mtb genome in context of gene products. We further combine IPW with STRING based network to report central proteins, which may be assessed as potential drug targets for development of drugs with least possible side effects. The fact that five of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lends credence to our unique approach.