Bilateral methicillin-resistant Staphylococcus aureus keratitis following hyperopic photorefractive surgery

To report clinical manifestations of a female patient with bilateral bacterial keratitis following photorefractive keratectomy (PRK). Bilateral PRK was performed for moderate hyperopia. Bandage contact lenses were fitted at the conclusion of the surgery. Bilateral infectious keratitis with hypopion was diagnosed within 4 days after surgery. Smear and culture were obtained and showed the presence of methicillin-resistant Staphylococcus aureus (MRSA). The patient was treated with systemic prednisone and topical antibiotics (vancomycin, tobramycin and netylmicin) and betamethasone. After 1 month corneal leukoma was still present and remained unchanged during the following 7 months. Infectious keratitis is a rare complication of PRK that appears early in the postoperative period. MRSA keratitis may determine long-term visual impairment despite prompt therapeutic intervention.     

Long-term effectiveness of autologous cultured limbal stem cell grafts in patients with limbal stem cell deficiency due to chemical burns

Background: Chemical burns cause depletion of limbal stem cells and eventually lead to corneal opacity and visual loss. We investigated the long‐term effectiveness of autologous cultured limbal stem cell grafts in patients with limbal stem cell deficiency. Design: Prospective, non‐comparative interventional case series. Participants: Sixteen eyes from 16 patients with severe, unilateral limbal stem cell deficiency caused by chemical burns. Methods: Autologous ex vivo cultured limbal stem cells were grafted onto the recipient eye after superficial keratectomy. Main Outcome Measures: Clinical parameters of limbal stem cell deficiency (stability/transparency of the corneal epithelium, superficial corneal vascularization and pain/photophobia), visual acuity, cytokeratin expression on impression cytology specimens and histology on excised corneal buttons. Results: At 12 months post‐surgery, evaluation of the 16 patients showed that 10 (62.6%) experienced complete restoration of a stable and clear epithelium and 3 (18.7%) had partially successful outcomes (re‐appearance of conjunctiva in some sectors of the cornea and instable corneal surface). Graft failure (no change in corneal surface conditions) was seen in three (18.7%) patients. Penetrating keratoplasty was performed in seven patients, with visual acuity improving up to 0.8 (best result). For two patients, regeneration of the corneal epithelium was confirmed by molecular marker (p63, cytokeratin 3, 12 and 19, mucin 1) analysis. Follow‐up times ranged from 12 to 50 months. Conclusions: Grafts of autologous limbal stem cells cultured onto fibrin glue discs can successfully regenerate the corneal epithelium in patients with limbal stem cell deficiency, allowing to perform successful cornea transplantation and restore vision.     

Radiofrequency combined with immunomodulation for hepatocellular carcinoma: State of the art and innovations

Hepatocellular carcinoma(HCC) is the most common primary liver tumor and has been considered a very immunogenic tumor. The treatment with radiofrequency ablation(RFA) has been established as the standard ablative therapy for early HCC, and is currently recognized as the main ablative tool for HCC tumors 5 cm in size; however, progression and local recurrence remain the main disadvantages of this approach. To solve this clinical problem, recent efforts were concentrated on multimodal treatment, combining different strategies, including the combination of RFA and immunotherapy. This article reviewed the combination treatment of RFA with immunotherapy and found that this treatment strategy leads to an increased response of anti-tumor T cells,significantly reduces the risk of recurrence and improves survival rates compared to RFA alone. This review highlighted scientific evidence that supports the current recommendations for pre-clinical studies, and discuss the need for further research on this topic.     

Na?ve and memory CD8 T cell pool homeostasis in advanced aging: impact of age and of antigen-specific responses to cytomegalovirus

Alterations in the circulating CD8+ T cell pool, with a loss of naïve and accumulation of effector/effector memory cells, are pronounced in older adults. However, homeostatic forces that dictate such changes remain incompletely understood. This observational cross-sectional study explored the basis for variability of CD8+ T cell number and composition of its main subsets: naïve, central memory and effector memory T cells, in 131 cytomegalovirus (CMV) seropositive subjects aged over 60 years. We found great heterogeneity of CD8+ T cell numbers, which was mainly due to variability of the CD8 + CD28− T cell subset regardless of age. Analysis, by multiple regression, of distinct factors revealed that age was a predictor for the loss in absolute number of naïve T cells, but was not associated with changes in central or effector memory CD8+ T cell subsets. By contrast, the size of CD8+ T cells specific to pp65 and IE-1 antigens of CMV, predicted CD28 − CD8+ T cell, antigen-experienced CD8+ T cell, and even total CD8+ T cell numbers, but not naïve CD8+ T cell loss. These results indicate a clear dichotomy between the homeostasis of naïve and antigen-experienced subsets of CD8+ T cells which are independently affected, in human later life, by age and antigen-specific responses to CMV, respectively.

Electronic supplementary material

The online version of this article (doi:10.1007/s11357-013-9594-z) contains supplementary material, which is available to authorized users.     

Sofosbuvir plus daclatasvir for post-transplant recurrent hepatitis C: Potent antiviral activity but no clinical benefit if treatment is given late

Background

We evaluated efficacy and safety of sofosbuvir and daclatasvir ± ribavirin in liver transplant recipients with severe recurrent hepatitis C.

Methods

Patients included in an international compassionate use programme for treatment with sofosbuvir and daclatasvir ± ribavirin for 24 weeks were prospectively studied. Serum hepatitis C virus RNA was measured at treatment weeks 4, 12, and 24 and during follow-up at weeks 4, 8, and 12.

Results

Twelve patients (3 with fibrosing cholestatic hepatitis and 9 with cirrhosis; median model for end-stage liver disease score 20) received sofosbuvir 400 mg/day + daclatasvir 60 mg/day, and 6 patients (50%) also received ribavirin 200–800 mg/day. Nine patients completed 24 weeks of treatment (75%), and all had undetectable hepatitis C virus RNA at week 24; 3 patients died (25%, liver failure, gastrointestinal bleeding and sepsis); 4 patients experienced severe liver disease-related adverse events. Post-treatment hepatitis C virus RNA was available for 5 patients (week 8, n = 2; week 4, n = 3) and was undetectable in all cases. Mean Child–Pugh score and albumin level improved significantly at week 24. No changes in immunosuppressant doses were needed.

Conclusion

All-oral sofosbuvir plus daclatasvir combination shows high virological efficacy in liver transplant recipients and does not interact with immunosuppressants. All adverse events were unrelated to study drugs. These data strongly suggest that this combination must be initiated before decompensation.     

Clinical and Immunological Outcome in Cutaneous Leishmaniasis Patients Treated with Pentoxifylline

Pentoxifylline is a tumor necrosis factor-α (TNF-α) inhibitor that also attenuates the immune response and decreases tissue inflammation. The association of pentoxifylline with antimony improves the cure rate of mucosal and cutaneous leishmaniasis. In this randomized and double blind pilot trial, cure rate was higher, although not significant, in patients who received antimony plus pentoxifylline than in those patients receiving antimony plus placebo. A significant decrease in TNF-α and interferon-γ (IFN-γ) levels during therapy was more pronounced in the antimony plus pentoxifylline group, whereas CCL-3 (Chemokine [C-C motif] ligand 3) decreased similarly in both groups. The increased levels of CXCL-9 (Chemokine [C-X-C motif] ligand 9) during therapy were lower in the antimony plus pentoxifylline group. Therapy with pentoxifylline modifies cytokines and chemokines production, which may be associated with therapeutic outcome.     

Quantitative culture of endotracheal aspirate and BAL fluid samples in the management of patients with ventilator-associated pneumonia: a randomized clinical trial

OBJECTIVE:

To compare 28-day mortality rates and clinical outcomes in ICU patients with ventilator-associated pneumonia according to the diagnostic strategy used.

METHODS:

This was a prospective randomized clinical trial. Of the 73 patients included in the study, 36 and 37 were randomized to undergo BAL or endotracheal aspiration (EA), respectively. Antibiotic therapy was based on guidelines and was adjusted according to the results of quantitative cultures.

RESULTS:

The 28-day mortality rate was similar in the BAL and EA groups (25.0% and 37.8%, respectively; p = 0.353). There were no differences between the groups regarding the duration of mechanical ventilation, antibiotic therapy, secondary complications, VAP recurrence, or length of ICU and hospital stay. Initial antibiotic therapy was deemed appropriate in 28 (77.8%) and 30 (83.3%) of the patients in the BAL and EA groups, respectively (p = 0.551). The 28-day mortality rate was not associated with the appropriateness of initial therapy in the BAL and EA groups (appropriate therapy: 35.7% vs. 43.3%; p = 0.553; and inappropriate therapy: 62.5% vs. 50.0%; p = 1.000). Previous use of antibiotics did not affect the culture yield in the EA or BAL group (p = 0.130 and p = 0.484, respectively).

CONCLUSIONS:

In the context of this study, the management of VAP patients, based on the results of quantitative endotracheal aspirate cultures, led to similar clinical outcomes to those obtained with the results of quantitative BAL fluid cultures.