A new class of bactericidal agents against S. aureus,MRSA and VRE derived from bisindolylmethane

A series of bisindolylmethanes (BIMs) (1a–7j) including hybrid BIMs 6a–6c were prepared for bioevaluation. The results of initial antimicrobial screening of compounds 1a–6c showed compounds 2b, 2m, 4a and 5b to be the most potent inhibitors, exhibiting MIC as well as MBC values equal to or less than that of ciprofloxacin (0.5–2 μg/mL) against Staphylococcus aureus, MRSA and VRE. Compound 2m was selected further to study the effect of N,N′ disubstitution towards antibacterial and antitumor activity. It was observed that substitution at N,N′ position (7a–7j) of 2m diminishes its antibacterial activity though in vitro antitumour activity against a panel of prostate, cervical and lung cancer cell lines remains more or less intact.     

Management of Early-stage Esophageal Neoplasia (MESEN) Consensus

Background

Treatment of esophageal adenocarcinoma often involves surgical resection. Newer technologies in interventional endoscopy have led to a substantial paradigm shift in the management of early-stage neoplasia in Barrett’s esophagus comprising high-grade dysplasia (HGD), intramucosal carcinoma, and, in some cases, submucosal carcinoma. However, there has been no consensus regarding the indications for esophageal preservation in these cases. In this work, consensus guidelines were established for the management of early-stage esophageal neoplasia considering clinically relevant aspects (age, comorbidities, and social environment) in each scenario.

Methods

Seventeen experts were invited to participate based on their background and clinical expertise at high-volume centers. A questionnaire was created that included four clinical scenarios covering a wide range of situations within HGD and/or early esophageal neoplasia, particularly where controversies are likely to exist. Each of the clinical scenarios was open to discussion subdivided by patient age (20, 50, and 80 s). For each clinical scenario an expert was chosen to defend that position. Each defense triggered a subsequent discussion during a consensus meeting. Conclusions of that discussion together with an accompanying literature analysis allowed experts to confirm or change their original choices and served as the basis for the recommendations stated in this article.

Results

There was 100 % consensus supporting esophageal preservation in patients with HGD, independent of patient age or Barrett’s length. In patients with T1a adenocarcinoma, consensus for preservation was not reached (65 %) for young and middle-aged individuals but was supported for elderly patients (100 %). For T1b adenocarcinoma, consensus was reached for surgical resection (90 %), leaving organ preservation for patients with very low risk of nodal invasion or poor surgical candidates.

Conclusion

Advances in endoscopic imaging and therapy allow for organ preservation in most settings of early-stage neoplasia of the esophagus, provided that the patient understands the implications of this decision.     

Long-Term Outcomes of Pancreas After Kidney Transplantation in Small Centers: Is It Justified?

Background

Currently, the long-term advantages of having a pancreas transplantation (PT) are debated, particularly in patients receiving pancreas after kidney (PAK) allografts. The United Network for Organ Sharing (UNOS) requires that a transplant center perform a minimum number of PT per year to remain an active PT center. The long-term outcomes and challenges of PAK in small pancreas transplant centers are not well studied.

Methods

In this retrospective analysis, we report short- and long-term outcomes in a small center performing 2–9 PT annually.

Results

Forty-eight PT (25 simultaneous pancreas and kidney transplantation [SPK], 23 PAK) were performed in our center. Donor and recipient demographics were similar in both groups. All suitable local donors were used for SPK. All organs for PAK transplantation were imported from other UNOS regions. Mean follow-up was 61 ± 46 and 74 ± 46 months for SPK and PAK, respectively. Patient and graft survival rates were similar in SPK and PAK groups and better than the reported national average. Four patients (11%) died (1 due to trauma, 1 brain lymphoma, 1 ruptured aneurysm; and 1 unknown cause). Two patients (4%; 1 SPK, 1 PAK) lost their grafts because of thrombosis on postoperative days 3 and 5 in 2002. No graft thrombosis occurred since 2002. Seven patients (15%) required reoperation (4 for bleeding, 2 anastomotic leaks, 1 small bowel perforation). Two patients (4%) developed post-transplantation lymphoproliferative disease. Five patients (11%) experienced cytomegalovirus antigenemia which responded well to antiviral therapy.

Conclusions

Compared with outcomes for diabetic patients on dialysis, current SPK and PAK short- and long-term results are favorable even in a small PT center. Therefore, unless there is a contraindication, PT should be offered to all type 1 diabetic patients with end-stage renal disease at the time of kidney transplantation or afterward.     

Fracture healing following high energy tibial trauma: Ilizarov versus Taylor Spatial Frame

Introduction

The optimal treatment of high energy tibial fractures remains controversial and a challenging orthopaedic problem. The role of external fixators for all these tibial fractures has been shown to be crucial.

Methods

A five-year consecutive series was reviewed retrospectively, identifying two treatment groups: Ilizarov and Taylor Spatial Frame (TSF; Smith & Nephew, Memphis, TN, US). Fracture healing time was the primary outcome measure.

Results

A total of 112 patients (85 Ilizarov, 37 TSF) were identified for the review with a mean age of 45 years. This was higher in women (57 years) than in men (41 years). There was no significant difference between frame types (p=0.83). The median healing time was 163 days in both groups. There was no significant difference in healing time between smokers and non-smokers (180 vs 165 days respectively, p=0.07), open or closed fractures (p=0.13) or age and healing time (Spearman''s r=0.12, p=0.18). There was no incidence of non-union or re-fracture following frame removal in either group.

Conclusions

Despite the assumption of the rigid construct of the TSF, the median time to union was similar to that of the Ilizarov frame and the TSF therefore can play a significant role in complex tibial fractures.     

Unusual presentation of Sturge-Weber syndrome: Progressive megalencephaly with bilateral cutaneous and cortical involvement

The Sturge Weber syndrome is characterized by developmental delay, seizures in infancy, unilateral cutaneous lesions with ipsilateral leptomeningeal enhancement. We report an unusual presentation of Sturge Weber syndrome with bilateral port wine nevus on the trunk and face along with bilateral cortical involvement in a developmentally normal child with progressive megalencephaly.     

Erb's paraplegia with primary optic atrophy: Unusual presentation of neurosyphilis: Case report and review of literature

Symptomatic neurosyphilis (NS) can have varied syndromic presentations: Meningitis, meningovascular and parenchymatous involvement. Non-tabetic syphilis affecting the spinal cord is rare and only sporadic case reports have been published. The variant of meningomyelitis known as Erb''s paraplegia refers to patients of spinal syphilis with very slow progression over many years and predominantly motor signs. Primary optic atrophy occurs twice as frequently in tabes dorsalis as in other types of NS. We describe here a case of a 32-year-old truck driver who presented with Erb''s paraplegia with primary optic atrophy. This clinical overlap in NS is extremely rare and to our knowledge is the first case report of its type.     

Blood Kidney Injury Molecule-1 Is a Biomarker of Acute and Chronic Kidney Injury and Predicts Progression to ESRD in Type I Diabetes

Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5–15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.