Outcomes of Unrelated Donor Stem Cell Transplantion with Post-Transplant Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients with Severe Sickle Cell Disease

Unrelated donor (URD) hematopoietic cell transplantation (HCT) in children with sickle cell disease (SCD) is associated with a high incidence of rejection and graft-versus-host disease (GVHD). We report on the first 4 patients with severe SCD who underwent URD HCT using a novel myeloablative and immunosuppressive regimen composed of busulfan, fludarabine, and antithymocyte globulin with a single dose of post-transplant cyclophosphamide along with tacrolimus and mycophenolate mofetil for GVHD prophylaxis. Three patients engrafted and remain disease-free after a median follow-up period of 2.5 years. One patient had primary graft failure attributed to low stem cell content of the graft. Of interest, none of the engrafted patients developed acute or chronic GVHD. This preparative regimen along with the use of post-transplant cyclophosphamide offers a promising approach for unrelated donor transplants in patients with SCD and needs further corroboration in larger number of patients.     

Role of dietary phenols in mitigating microglia-mediated neuroinflammation

Chronic neuroinflammation is a pathological feature of a number of central nervous system (CNS) diseases and is mediated by sustained activation of microglial cells, the innate immune cells of the CNS. Studies have mainly focused on identifying the molecular and epigenetic mechanisms of microglial activation. This is crucial in designing therapeutic strategies for neuropathologies in which prolonged microglial activation is known to exacerbate disease condition. In recent years, increasing evidence show that naturally occurring compounds present in regular diet could function as “nutraceuticals,” arresting microglial activation, and thus conferring neuroprotection. This review summarizes our understanding of the role of dietary phenolic nutraceuticals in mitigating microglia-mediated neuroinflammation. Studies show that these natural phenols inhibit key signaling pathways in activated microglia such as the NFκB, MAPK and JAK-STAT that trigger microglia-mediated inflammation in various neuropathological conditions such as injury, infection, stroke, autism and neurodegenerative diseases, i.e., Alzheimer’s disease and Parkinson’s disease. The anti-inflammatory and antioxidant effect exerted by these natural phenols have shown considerable success in improving disease condition in animal models of neuropathologies, and thus seem to be suitable candidates for developing therapeutic strategies.     

Restless legs syndrome in an Indian urban population

BACKGROUND: The prevalence of restless legs syndrome (RLS) in India is unknown. OBJECTIVES: The primary objective was to assess the occurrence of RLS in residents of Bangalore. The secondary objective was to correlate demographic and socioeconomic factors with RLS occurrence and severity. METHODS: This was a cross-sectional, questionnaire-based survey conducted during August 2005 among adult residents of Bangalore, who participated in a face-to-face interview. Diagnosis of RLS was based on fulfillment of all National Institutes of Health/International Restless Legs Syndrome Study Group (NIH/IRLSSG) essential criteria. Severity of RLS was assessed using the IRLSSG scale. RESULTS: RLS occurred in 27 (2.1%) of 1266 respondents. Predominant symptoms included "pulling," "tingling" and "pain". RLS was associated with delayed sleep onset and RLS severity correlated with the duration of delay in sleep onset. RLS was associated with per-capita income less than the equivalent of US$1/day, education less than high school level, chronic daily alcohol consumption and chronic blood loss. CONCLUSION: This is the first Indian population study on RLS which reveals prevalence of the disorder in a South Indian urban population at 2.1%. Larger studies are warranted to better characterize RLS in India.     

Pathogen Profiling: Rapid Molecular Characterization of Staphylococcus aureus by PCR/Electrospray Ionization-Mass Spectrometry and Correlation with Phenotype

There are few diagnostic methods that readily distinguish among community-acquired methicillin (meticillin)-resistant Staphylococcus aureus strains, now frequently transmitted within hospitals. We describe a rapid and high-throughput method for bacterial profiling of staphylococcal isolates. The method couples PCR to electrospray ionization-mass spectrometry (ESI-MS) and is performed on a platform suitable for use in a diagnostic laboratory. This profiling technology produces a high-resolution genetic signature indicative of the presence of specific genetic elements that represent distinctive phenotypic features. The PCR/ESI-MS signature accurately identified genotypic determinants consistent with phenotypic traits in well-characterized reference and clinical isolates of S. aureus. Molecular identification of the antibiotic resistance genes correlated strongly with phenotypic in vitro resistance. The identification of toxin genes correlated with independent PCR analyses for the toxin genes. Finally, isolates were correctly classified into genotypic groups that correlated with genetic clonal complexes, repetitive-element-based PCR patterns, or pulsed-field gel electrophoresis types. The high-throughput PCR/ESI-MS assay should improve clinical management of staphylococcal infections.Invasive infections caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) are among the most common complications of health care in the United States. Klevens et al. estimate that 94,360 invasive MRSA infections occur in the United States each year, with associated deaths in 18,650 cases (26). Infections are subcategorized as health care-associated MRSA (HA-MRSA) infections or as community-associated MRSA (CA-MRSA) infections; the latter occur in otherwise healthy people who have not experienced a hospital stay within the past 12 months (24, 35). CA-MRSA infections have largely been attributable to a few strains, designated pulsed-field types (PFTs) USA300 and USA400 (26, 29). Once introduced into a health care environment, CA-MRSA strains can be readily transmitted, blending with or replacing entrenched HA-MRSA strains (25, 35).Microbial genotyping analysis allows investigation into the clonality of an outbreak and risk factors associated with infection (5). Methods such as pulsed-field gel electrophoresis (PFGE) (39), repetitive-element-based PCR (rep-PCR) (42), and multilocus sequence typing (MLST) (10, 11) are used for microbial genotyping but are costly and labor-intensive and do not enable specific characterization of acquired genetic elements encoding virulence factors or toxins or of genes that mediate antibiotic resistance (40). A rapid technique for determining the MRSA strain genotype and its broader complement of genetic elements would enable a more comprehensive understanding of transmission dynamics and could lead to more effective actionable decisions related to bed management, prioritization of infection control resources, and treatment.Here, we describe the use of a rapid and high-throughput method to simultaneously genotype and characterize S. aureus specimens with respect to acquired genes encoding virulence factors, toxins, and antibiotic resistance determinants. The method is based on PCR coupled to electrospray ionization-mass spectrometry (ESI-MS) (8, 22, 37).The PCR/ESI-MS assay uses several novel strategies. First, broad-range primers, targeting sites that are highly conserved in all members of a microbe family, are used to amplify PCR products from groupings of microbes rather than single species. These primers are coupled with species- or strain-specific primers for the identification of specific pathogens or antibiotic targets. Second, PCR conditions are, by design, permissive and thus tolerant of mismatches, so that even sequences from novel strains can be amplified. Third, inosine and other “wild-card” nucleotides are used in primers to facilitate PCR analysis of mispaired sequences. Fourth, because MS simply measures the mass-to-charge ratio (m/z), the sequence of the amplicon need not be known in order to detect it. The technology offers advantages over routine single-target and multiplex PCR in that it is a full bioinformatics sequence analysis system.After amplification, MS is used to rapidly determine the precise mass-to-charge ratio for the amplified nucleic acid fragments present, and the A, C, T, and G contents (i.e., the base composition) of each amplicon are determined using proprietary software that creates a signature to allow organism identification and genotyping. This novel MS technology enables the rapid, sensitive, cost-effective, and simultaneous detection of a wide range of typical pathogenic organisms.We used the PCR/ESI-MS assay to analyze a well-characterized set of S. aureus strains from the CDC and geographically distinct clinical isolates from Maryland and Arizona. The PCR/ESI-MS technology effectively combines genotyping and characterization on a single high-throughput platform suitable for surveillance, infection control interventions, and patient management.     

"Very Late" isolated para-aortic nodal recurrence of carcinoma cervix mimicking radiation-induced sarcoma

Only a minority of the patients who develop recurrence after definitive treatment for cervical cancer are detected after 5 years (late recurrence); the numbers are lesser still after 10 years (very late recurrence). Among the infrequent cases that do develop "late" and "very late" recurrence, the commonest site is the pelvis. We report an unusually rare recurrence of treated cervical cancer confined to the para-aortic nodal group after a protracted disease-free interval of 13 years. On the basis of the long disease-free interval, location of the mass at the periphery of the radiation field, and aggressive imaging appearance, a diagnosis of radiation-induced sarcoma was considered. However, the final diagnosis of isolated para-aortic nodal recurrence of cervical cancer was rendered based on the histopathological and immunohistochemistry findings, supported by the absence of disease elsewhere on whole-body imaging.     

Textpresso for Neuroscience: Searching the Full Text of Thousands of Neuroscience Research Papers

Textpresso is a text-mining system for scientific literature. Its two major features are access to the full text of research papers and the development and use of categories of biological concepts as well as categories that describe or relate objects. A search engine enables the user to search for one or a combination of these categories and/or keywords within an entire literature. Here we describe Textpresso for Neuroscience, part of the core Neuroscience Information Framework (NIF). The Textpresso site currently consists of 67,500 full text papers and 131,300 abstracts. We show that using categories in literature can make a pure keyword query more refined and meaningful. We also show how semantic queries can be formulated with categories only. We explain the build and content of the database and describe the main features of the web pages and the advanced search options. We also give detailed illustrations of the web service developed to provide programmatic access to Textpresso. This web service is used by the NIF interface to access Textpresso. The standalone website of Textpresso for Neuroscience can be accessed at .     

Laparoscopic Management of a Retroperitoneal Duodenal Perforation Following ERCP for Periampullary Cancer

Introduction:

Endoscopic retrograde cholangiopancreatography (ERCP) is a fairly common procedure being performed in several centers worldwide. Although it is proven to be efficient and relatively safe, complications do occur (1.8%). We present a patient with ERCP-induced retroperitoneal perforation of the duodenum treated laparoscopically at our institution.

Case Report:

The patient is a 60-year-old female who underwent ERCP for obstructive jaundice due to periampullary carcinoma, during which the perforation occurred. Laparoscopy was performed 5 hours later and the perforation sutured primarily.

Results:

The operating time was 125 minutes. On the fourth postoperative day, the patient developed a retroperitoneal collection, confirmed by computed tomographic scan. Re-look laparoscopy was performed and the fluid drained. She recovered completely and was discharged on the eighth postoperative day.

Conclusion:

Duodenal perforation following ERCP is rare, with an incidence of 1.8%. Both surgical and non-surgical management have been reported, each with its specific indications. Our patient needed surgery, because the perforation was large and a retroperitoneal collection was present. Laparotomy is the preferred approach, though now laparoscopy is a viable and effective alternative, because it provides the benefits of minimal access, such as reduced pain and early ambulation.     

Transumbilical endoscopic appendectomy in humans: on the road to NOTES: a prospective study

BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) is the newest technique emerging in the field of surgery. There are several techniques described in the literature, though there is no standardization yet. In this paper, we describe a transumbilical approach for the endoscopic appendectomy in humans. MATERIALS AND METHODS: Eight of 12 patients with uncomplicated appendicitis successfully underwent a transumbilical endoscopic appendectomy. Patients with a mass, abscessed or perforated appendix, previous lower abdominal surgeries, and conversion to laparoscopy (4 patients) were excluded. RESULTS: The average age of the patients was 32.5 years. The mean operating time was 95 minutes, and the conversion rate was 33.3%. Only 1 dose of intravenous analgesics was administered postoperatively. Hospital stay was 1-3 days. The follow-ups were scheduled at 7, 30, and 90 days and 8 months. Six patients completed all the follow-ups and experienced no problems. DISCUSSION: So far, this transumbilical approach to the appendectomy in humans has not been reported. We think that this method of approach is an effective technique by itself and an ideal "stepping stone" to NOTES, as well as helpful to train laparoscopic surgeons to make the transition to full-fledged NOTES. Unlike the transgastric or transvaginal approaches, the umbilical approach allows an easy maneuverability of the endoscope, though at the cost of an umbilical scar. The technical ease of the procedure and early outcome seem satisfactory. This technique may be considered as a "precursor" to NOTES.     

Laparoscopic and perineal excision of an infected "dumb-bell" shaped retrorectal epidermoid cyst

INTRODUCTION: Extraperitoneal cysts in the pelvis adjacent to the rectum are rare entities. They are of vague etiology, and the pathologic types of the acquired variety are dermoid, epidermoid, and teratoma. As far as we know, laparoscopic excision of a retrorectal epidermoid cyst has never before been reported. CASE REPORT: The patient was an elderly lady with a large pelvic cyst and another large cyst in the perineum, which displaced the vagina and the anus. Laparoscopy was performed; the pelvic cyst was punctured and then dissected out. The perineal extension of the cyst was excised via a perineal approach. The patient had an uneventful recovery and was discharged on the 4th postoperative day. Histopathologically, the cyst was of the epidermoid type. Follow-up after 26 months revealed no recurrence. DISCUSSION: Our case presented a diagnostic dilemma. Laparoscopic excision was tedious, though we completed the procedure successfully. Precaution was taken to avoid spillage of the contents and also to avoid injury to vital structures nearby, such as the iliac vessels and ureter. It is feasible to laparoscopically excise retrorectal cysts with a careful and meticulous dissection. CONCLUSIONS: The major advantages are rapid recovery with minimal morbidity and excellent cosmesis.     

Laparoscopic management of drain-site incisional hernias following laparotomies--a simple suture technique

BACKGROUND: Herniation through drain sites is a rare but recognized complication of surgical drainage and are actually considered to be a type of incisional hernia. Incisional hernias form following surgery through the incision site or previous drain sites, or through laparoscopic trocar insertion sites. PATIENTS AND METHODS: In this paper, we present 13 such patients with incisional hernia of the main laparotomy wound and at the drain site, and 1 patient with an isolated drain-site hernia. A laparoscopic meshplasty with a simple suturing of the drain-site defect was performed. DISCUSSION: Incisional hernias are reported to occur in approximately 4%-10% of patients following open surgical procedures. There are several studies that have proven the efficacy of laparoscopic repair of incisional hernias, when compared to open procedures. The main predisposing factor regarding incisional hernias is probably the presence of a sepsis during the previous laparotomy, which was why the drainage tube was kept in the first place. CONCLUSIONS: The laparoscopic approach is useful for repairing the main incisional hernia, as well as drain-site hernias, simultaneously. We cut costs by avoiding tacking devices and use intracorporeal suturing instead.