The purpose of this meta-analysis was to compare postprocedural mortality and major adverse cardiovascular and cerebrovascular events between transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) for severe aortic stenosis. Seventeen studies (n = 4,659) comparing TAVI (n = 2,267) and SAVR (n = 2,392) were included. End points were baseline logistic European System for Cardiac Operative Risk Evaluation score, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, transient ischemic attack, and major bleeding events. Mean differences or risk ratios with 95% confidence intervals were computed, and p values <0.05 were considered significant. The population was matched for risk between the 2 groups on the basis of logistic European System for Cardiac Operative Risk Evaluation score for all outcomes except 30-day all-cause mortality, which had a high-risk population in the TAVI group (p = 0.02). There was no significant difference found in all-cause mortality at 30 days (p=0.97) and at an average of 85 weeks (p=0.07). There was no significant difference in cardiovascular mortality (p=0.54) as well as the incidence of myocardial infarction (p=0.59), stroke (p=0.36), and transient ischemic attack (p = 0.85) at averages of 86, 72, 66, and 89 weeks, respectively. Compared with patients who underwent TAVI, those who underwent SAVR had a significantly higher frequency of major bleeding events (p <0.0001) at mean follow-up of 66 weeks. In conclusion, TAVI has similar cardiovascular and all-cause mortality to SAVR at early and long-term follow-up. TAVI is superior to SAVR for major bleeding complications and noninferior to SAVR for postprocedural myocardial infarctions and cerebrovascular events. TAVI is a safe alternative to SAVR in selected high-risk elderly patients with severe aortic stenosis.

Human monocytes/macrophages (M/MΦ) of the innate immunity sense and respond to microbial products via specific receptor coupling with stimulatory (such as TLR) and inhibitory (such as Tim-3) receptors. Current models imply that Tim-3 expression on M/MØ can deliver negative signaling to TLR-mediated IL-12 expression through trans association with its ligand Galectin-9 (Gal-9) presented by other cells. However, Gal-9 is also expressed within M/MØ, and the effect of intracellular Gal-9 on Tim-3 activities and inflammatory responses in the same M/MØ remains unknown. In this study, our data suggest that Tim-3 and IL-12/IL-23 gene transcriptions are regulated by enhanced or silenced Gal-9 expression within monocytes through synergizing with TLR signaling. Additionally, TLR activation facilitates Gal-9/Tim-3 cis association within the same M/MØ to differentially regulate IL-12/IL-23 expressions through STAT-3 phosphorylation. These results reveal a ligand (Gal-9) compartment-dependent regulatory effect on receptor (Tim-3) activities and inflammatory responses via TLR pathways-a novel mechanism underlying cellular responses to external or internal cues.

Drug-resistant gonorrhea, Neisseria gonorrhoeae (N. gonorrhoeae), is an emerging concern, especially because the risk of bladder cancer is associated with this infection. N. gonorrhoeae suppresses T-helper 1(Th1) and Th2 responses and enhances Th17 responses via a mechanism involving transforming growth factor-beta (TGF-β) and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with concomitant boosting of immune memory and protective immunity. Gonorrhea activates nuclear factor kappaB (NF-kappaB), which plays a critical role in signal-transduction pathways involved in inflammation. The innate immune system can eventually clear gonorrhea. Vitamin D is emerging as a potential, powerful, anti-microbial agent with these effects: it supports the innate immune system in combating bacterial infections; it decreases levels of TGF-β and NF-kappaB activation; and it induces production of LL-37 (cathelicidin), which has antimicrobial and antiendotoxin properties. In addition, via an independent vitamin D receptor pathway, curcumin also induces LL-37 production, inhibiting N. gonorrhoeae-induced NF-kappaB signaling and inducing autophagy. Therefore, vitamin D and curcumin taken together may be useful in combating both normal and drug-resistant gonorrhea. Moreover, the possible synergy between these two agents in improving outcomes is worthy of additional investigation.

Cytokine production by innate immunity is critical for shaping the adaptive immunity through regulation of T cell differentiation. In this report, we studied T cell immunoglobulin mucin domain protein 3 (Tim-3) expression on monocytes and its regulatory effect on interleukin-12 (IL-12)/IL-23 production by CD14+ monocytes, as well as IL-17 production by CD4+ T cells in individuals with chronic hepatitis C virus (HCV) infection. We found that Tim-3 and IL-23p19 are highly expressed and that IL-12p35 is inhibited in human CD14+ monocytes, while IL-17 expression is upregulated in CD4+ T cells, in chronically HCV-infected individuals compared to healthy subjects. Interestingly, Tim-3 expression is closely associated with the differential regulation of IL-12/IL-23 expression in CD14+ monocytes and correlated to IL-17 production by CD4+ T cells. These Tim-3- associated IL-12/IL-23/IL-17 dysregulations in HCV-infected individuals are also recapitulated in vitro by incubating healthy monocytes or peripheral blood mononuclear cells with Huh-7 hepatoma cells transfected with HCV RNA. Importantly, blocking Tim-3 signaling on monocytes restores the balance of IL-12/IL-23 through the intracellular STAT3 signaling, which in turn reverses the upregulated IL-17 expression both ex vivo and in vitro. Our findings suggest that Tim-3-mediated differential regulation of IL-12/IL-23 drives TH17 cell development, a milieu favoring viral persistence and autoimmune phenomenon during HCV infection.

No description available.

Introduction. Non Hodgkin lymphoma (NHL) presenting with obstructive jaundice is a rare occurrence. Because of rarity of combination, it is seldom considered in differential diagnosis of patients presenting with obstructive jaundice. It is considered treatable due to the chemosensitive nature of the disease and the recent advances in chemotherapy. Case Series. We present a case series of 2 patients with NHL presenting with obstructive jaundice as an initial manifestation. Both patients presented with obstructive jaundice and were diagnosed by CT guided liver biopsy. One patient died of sepsis and multiorgan failure before initiating chemotherapy and the second patient did not choose to undergo chemotherapy. Conclusion. Biliary obstruction is a sign of poor prognosis. The diagnosis of NHL needs to be considered in patients presenting with biliary obstruction. It can be associated with high mortality and poses treatment dilemma.

Microscopic Colitis (MC) is characterized by chronic watery diarrhea, grossly normal appearing colonic mucosa during conventional white light endoscopy, and biopsy showing microscopic inflammation. We report a case of collagenous colitis with gross endoscopic findings.

We are reporting a case of a 63-year-old-male patient with an unusual presentation of multiple lung abscesses. The patient likely had septic pulmonary emboli secondary to periodontal disease. The implicated organism was Veillonella species. Veillonella are anaerobe bacteria that traditionally been considered nonpathogenic flora.

Diabetes mellitus is increasing in frequency and is associated with disabling acute and chronic complications. There is evidence to indicate that excellent glucose control may retard the development and/or progression of these complications. In order to optimize diabetic control, patients are encouraged to monitor their glucose frequently. We describe a patient who provided inaccurate glucose monitoring results, delaying effective management of hisprogressively increasing glycosylated hemoglobin level. The diagnostic due to his erroneous glucose monitoring results was the lack of intra-day variation in this patient on insulin therapy. Moreover, glucose records within the patient's glucometer pointed to a much less frequent glucose monitoring than the written data provided by the patient. The glucometer was accurate when used by the patient under direct observation. It remains unclear whether this patient deliberately misled his providers or if the erroneous data reflected underlying cognitive dysfunction. Providers are encouraged to approximate average blood sugars based on glycosylated hemoglobin values and compare this to home monitoring results provided by the patient. Primary providers should also expect a certain degree of variability when reviewing home blood sugar values with their patients (on insulin therapy) and consider further investigation should the numbers lack such variation. Clinicians are urged to inspect the actual glucose readings on the patient's glucometer as well as inspecting written glucoserecords. Observing the patient's technique and accuracy when using their personal glucometer should also be considered.

Sildenafil, usually a well-tolerated drug traditionally used for erectile dysfunction (ED), was recently approved for pulmonary arterial hypertension. In the literature, there are few cases of hemoptysis following sildenafil use for ED; however, to our knowledge, we are reporting the first case of hemoptysis following sildenafil use for pulmonary hypertension. We are documenting a case of a 90-year-old male patient who was admitted to the intensive care unit with hemoptysis and respiratory failure two weeks after he was started on sildenafil.