Systematic review of guidelines for the assessment and management of high-grade anal intraepithelial neoplasia (AIN II/III).

AIM: There is ambiguity with regard to the optimal management of anal intraepithelial neoplasia (AIN) III. The aim of this review was to assess and compare international/national society guidelines currently available in the literature on the management, treatment and surveillance of AIN III. We also aimed to assess the quality of the studies used to compile the guidelines and to clarify the terminology used in histological assessment. METHOD: An electronic search of PubMed and Embase was performed using the search terms 'anal intraepithelial neoplasia', 'AIN', 'anal cancer', 'guidelines', 'surveillance' and 'management'. Literature reviews and guidelines or practice guidelines in peer reviewed journals from 1 January 2000 to 31 December 2014 assessing the treatment, surveillance or management of patients with AIN related to human papilloma virus were included. The guidelines identified by the search were assessed for the quality of evidence behind them using the Oxford Centre for Evidence-based Medicine 2011 Levels of Evidence. RESULTS: The database search identified 5159 articles and two further guidelines were sourced from official body guidelines. After inclusion criteria were applied, 28 full-text papers were reviewed. Twenty-five of these were excluded, leaving three guidelines for inclusion in the systematic review: those published by the Association of Coloproctology of Great Britain and Ireland, the American Society of Colon and Rectal Surgeons and the Italian Society of Colorectal Surgery. No guidelines were identified on the management of AIN III from human papilloma virus associations and societies. All three guidelines agree that a high index of clinical suspicion is essential for diagnosing AIN with a disease-specific history, physical examination, digital rectal examination and anal cytology. There is interchange of terminology from high-grade AIN (HGAIN) (which incorporates AIN II/III) and AIN III in the literature leading to confusion in therapy use. Treatment varies from immunomodulation and photodynamic therapy to targeted destruction of areas of HGAIN/AIN II/III using infrared coagulation, electrocautery, cryotherapy or surgical excision but with little consensus between the guidelines. Recommendations on surveillance strategies are similarly discordant, ranging from 6-monthly physical examination to annual anoscopy ± biopsy. Over 50% of the recommendations are based on Level 3 or Level 4 evidence and many were compiled using studies that were more than 10 years old. CONCLUSION: Despite concordance regarding diagnosis, there is significant variation in the guidelines over recommendations on the treatment and surveillance of patients with HGAIN/AIN II/III. All three sets of guidelines are based on low level, outdated evidence originating from the 1980s and 1990s.

Delayed absorbable synthetic plug (GORE® BIO-A®) for the treatment of fistula-in-ano: a systematic review.

AIM: Recent advances in the treatment of fistula-in-ano have focused on surgical techniques that preserve sphincter integrity. Plugs that obliterate the lumen of the fistula track have been proposed as one such method, and may be derived from biological or delayed absorbable synthetic materials. Biological plugs have highly variable results and have not been widely adopted. The aim of this systematic review was to assess the effectiveness and safety of a delayed absorbable synthetic plug (GORE® BIO-A®) for treatment of anal fistula. METHOD: A systematic review of all literature in the English language relevant to the use of a plug to treat anal fistula and published between 1 January 2008 and 15 February 2015 was carried out by searching MEDLINE, EMBASE and the Cochrane Library of Systematic Reviews/Controlled Trials for relevant literature. Relevant articles were identified, quality assessed using the methodological index for nonrandomized studies criteria and data were extracted by two independent researchers (SKN and NNA). The identified articles were assessed with regard to fistula healing rate, duration of follow-up and complication rates related to the use of delayed absorbable synthetic fistula plugs. RESULTS: Twenty six potential articles were identified from the literature search. Using the predefined inclusion and exclusion criteria, six were included in the final analysis, data extraction and data synthesis. Of these included in the review only three were prospective in design. Complete data were available for 187 of the 221 patients who underwent this treatment. The age of the participants ranged from 19 to 82 years. The fistula healing rates were reported to be between 15.8% and 72.7% at a follow-up ranging between 2 and 19 months. Early or delayed plug extrusion occurred in 16 (8.5%) of the 187 patients. Deterioration in continence was reported in 11 (5.8%) of 187 patients. CONCLUSION: There are insufficient high-quality data on the delayed absorbable synthetic (GORE® BIO-A®) fistula plug to draw meaningful conclusions regarding its effectiveness. It does, however, appear to be a simple and safe technique associated with low complication rates and a minor deterioration in continence in a few cases.

Overturned abusive head trauma and shaken baby syndrome convictions in the United States: Prevalence, legal basis, and medical evidence.

BACKGROUND: Media reports and the Innocence Network assert that wrongful Abusive Head Trauma (AHT)/Shaken Baby Syndrome (SBS) convictions pervade the United States (U.S.) criminal justice system. Yet, no empirical evaluation of overturned AHT/SBS convictions has been conducted. OBJECTIVE: To evaluate the prevalence, legal basis, and characteristics of appellate rulings of AHT/SBS convictions. PARTICIPANTS AND SETTING: U.S. appellate cases in a legal database, Westlaw. METHODS: Retrospective review of AHT/SBS convictions that had appellate rulings from January 2008 through December 2018. Multiple search terms ensured all potential AHT/SBS cases were included. A mixed-methods analysis was conducted on overturned AHT/SBS convictions. RESULTS: We identified a total of 1431 unique AHT/SBS criminal convictions that had appellate rulings since 2008. Of those, 49 convictions (3%) were overturned, and 1382 (97%) were affirmed/upheld. Of those overturned, 20 cases (1% overall) were overturned on medical evidence-related grounds. The most common themes from the medical evidence-related reversals were controversy over the AHT/SBS diagnosis (n = 12) and accidental injury mechanism (n = 11). After being overturned on appeal, upon retrial, 42% of defendants either re-plead guilty to or were convicted again of the same offense. CONCLUSION(S): AHT/SBS convictions are rarely overturned on medical evidence-related grounds. When overturned, medical evidence-related themes seldom reflect new scientific or clinical discoveries, but rather are alternative or differing medical opinions from those offered at the original trial. Our data tends to support the concerns of other authors regarding irresponsible communication of medical information in AHT/SBS cases.

What is the evidence for the use of biologic or biosynthetic meshes in abdominal wall reconstruction?

INTRODUCTION: Although many surgeons have adopted the use of biologic and biosynthetic meshes in complex abdominal wall hernia repair, others have questioned the use of these products. Criticism is addressed in several review articles on the poor standard of studies reporting on the use of biologic meshes for different abdominal wall repairs. The aim of this consensus review is to conduct an evidence-based analysis of the efficacy of biologic and biosynthetic meshes in predefined clinical situations. METHODS: A European working group, "BioMesh Study Group", composed of invited surgeons with a special interest in surgical meshes, formulated key questions, and forwarded them for processing in subgroups. In January 2016, a workshop was held in Berlin where the findings were presented, discussed, and voted on for consensus. Findings were set out in writing by the subgroups followed by consensus being reached. For the review, 114 studies and background analyses were used. RESULTS: The cumulative data regarding biologic mesh under contaminated conditions do not support the claim that it is better than synthetic mesh. Biologic mesh use should be avoided when bridging is needed. In inguinal hernia repair biologic and biosynthetic meshes do not have a clear advantage over the synthetic meshes. For prevention of incisional or parastomal hernias, there is no evidence to support the use of biologic/biosynthetic meshes. In complex abdominal wall hernia repairs (incarcerated hernia, parastomal hernia, infected mesh, open abdomen, enterocutaneous fistula, and component separation technique), biologic and biosynthetic meshes do not provide a superior alternative to synthetic meshes. CONCLUSION: The routine use of biologic and biosynthetic meshes cannot be recommended.

Methods of abdominal wall expansion for repair of incisional herniae: a systematic review.

AIM: To systematically review the available literature regarding methods for abdominal wall expansion and compare the outcome of primary fascial closure rates. METHODS: A systematic search of Pubmed and Embase databases was conducted using the search terms "Abdominal wall hernia", "ventral hernia", "midline hernia", "Botulinum toxin", "botox", "dysport", "progressive preoperative pneumoperitoneum", and "tissue expanders". Study quality was assessed using the Methodological Index for Non-Randomised Studies. RESULTS: 21 of the 105 studies identified met the inclusion criteria. Progressive preoperative pneumoperitoneum (PPP) was performed in 269 patients across 15 studies with primary fascial closure being achieved in 226 (84%). 16 patients had a recurrence (7.2%) and the complication rate was 12% with 2 reported mortalities. There were 4 studies with 14 patients in total undergoing abdominal wall expansion using tissue expanders with a fascial closure rate of 92.9% (n = 13). A recurrence rate of 10.0% (n = 1) was reported with 1 complication and no mortalities. Follow up ranged from 3 to 36 months across the studies. There were 2 studies reporting the use of botulinum toxin with 29 patients in total. A primary fascial closure rate of 100% (n = 29) was demonstrated although a combination of techniques including component separation and Rives-Stoppa repair were used. There were no reported complications related to the use of Botulinum Toxin. However, the short-term follow up in many cases and the lack of routine radiological assessment for recurrence suggests that the recurrence rate has been underestimated. CONCLUSIONS: PPP, tissue expanders and Botulinum toxin are safe and feasible methods for abdominal wall expansion prior to incisional hernia repair. In combination with existing techniques for repair, these methods may help provide the crucial extra tissue mobility required to achieve primary closure.

Dichotomous electrophoretic taxonomic key for identification of sibling species A, B, and C of the Anopheles quadrimaculatus complex (Diptera: Culicidae).

Samples of 17 populations of Anopheles quadrimaculatus Say from Florida, Alabama, Arkansas, Louisiana, Mississippi, Tennessee, New York, and New Jersey were analyzed for genetic variability at 33 enzyme loci. Statistical analysis of electromorph frequency distributions indicated that sympatric sibling (morphologically indistinguishable) species occurred in about 59% of the populations tested. The association of polytene chromosome and electrophoretic patterns of individual field-collected females confirmed species-specific diagnostic allozymes, which were useful in identifying sibling species A, B, and C and in estimating the proportions of each species at the 17 collection sites. A dichotomous electrophoretic key is presented for the identification of sibling species of the An. quadrimaculatus complex. The electrophoretic method is better than the ovarian polytene chromosome method, because mosquitoes of both sexes and females irrespective of their gonotrophic condition can be identified.

In situ hybridization mapping of histone genes in Anopheles albimanus.

The histone genes of Anopheles albimanus were mapped by in situ hybridization to 6 bands in Region 34A on the right arm of chromosome 3. A genomic library was made by cloning fragments of 15 to 23 kb (derived from partial EcoRI digestion) into the phage vector, EMBL4, and probed with the histone gene repeat of Drosophila melanogaster. Thirty-two phages containing histone gene sequences were isolated from about 10(5) plaque-forming units (pfu). Complete EcoRI digestion of DNA from 5 of the 32 recombinant phages and the genomic DNA of An. albimanus yielded a single 3.84-kb fragment that contained sequences homologous to the 5 histone genes of D. melanogaster. This 3.84-kb unit of mosquito histone genes was subcloned into puc19 plasmid, and the resulting clone (palbi34A) was used for in situ hybridization to salivary gland chromosomes.

Hexane preserves biological activity of isozymes and DNA.

Live or frozen insects are required for using isozyme and DNA RFLP methods in studies on population structure, systematics and incrimination of sibling species. Difficulty in keeping insects alive or unavailability of liquid nitrogen or dry ice at regular intervals during extended collection trips poses a serious problem. We describe a method for preserving insects in hexane, under field conditions, for isozyme and DNA analysis.

Genetic structure of natural populations of Anopheles albimanus in Colombia.

Electrophoretic and cytogenetic studies were undertaken on the population structure of Anopheles albimanus from 11 localities in Colombia, 3 from northern (Atlantic coast) and 8 from southern (Pacific coast) regions. Of the 25 allozyme loci examined, significant allele frequency differences were observed at 4 loci: hydroxy acid dehydrogenase (Had-1) and 3 esterases (Est-2, Est-4 and Est-6). The northern populations had higher variability, with 55% polymorphic loci, a mean heterozygosity of 20.4% and a mean of 3.0 alleles per locus. These values for southern populations were 24%, 9.1% and 1.5%, respectively. There were neither diagnostic loci nor clinal effect on frequencies of allozymes. Except for a small inversion on the X chromosome in low frequency in certain populations, all populations were homosequential in chromosomal banding patterns. Hybrids from matings between natural populations and the Gainesville laboratory strain were fully fertile. Estimates of genetic similarities (0.95-0.97 among southern and 0.99-1.00 among northern populations) suggest a lack of significant genetic differentiation among distant populations in this species. Based on the chromosomal, hybridization and electrophoretic data, we concluded that mosquitoes from the 11 collections were conspecific populations of An. albimanus.

Evidence for microgeographic genetic subdivision of Anopheles quadrimaculatus species C.

Species C of the Anopheles quadrimaculatus complex has a patchy distribution and has been found principally near the coast in river and springs systems of northwest Florida (GULF, SR, SFR--designated as C1, and CHOC--designated as C2) and the Ogeechee River (OGE--C2) near Savannah, Georgia. We have documented significant differences in allelic frequencies at 5 loci (malic enzyme, aconitase, aldehyde oxidase, esterase-5 and esterase-6), and genetic substructuring (Fst) between C1 and C2. The GULF and CHOC populations occurred in apparently similar environments, but were separated by about 160 km. Both these populations are separated from OGE by over 160 km (with low to undetectable distribution of species C in the transect regions). The higher genetic similarity of the CHOC with OGE populations indicated either selective pressures or genetic drift or both as being responsible for the differences between C1 and C2 populations.

Identification of species D, a new member of the Anopheles quadrimaculatus species complex: a biochemical key.

Sibling species D, a new member of the Anopheles quadrimaculatus species complex was identified in collections from Pickwick Lake, Tishomingo County, Mississippi and Choctawhatchee, Bay County, in West Florida. This species occurred sympatrically with the previously described species, A, B and C. Evidence for identification of species D includes diagnostic allozymes, a lack of polytene chromosomes in the ovarian nurse cells, and inviability of F1 progeny and lack of sperm transfer in hybridization crosses. An electrophoretic taxonomic key for distinguishing species D from A, B and C is presented.

A simple method for shipping field collected mosquitoes for electrophoretic studies.

A method for preserving field collected material in frozen condition for electrophoresis is described. A mixture of ice and salt was used to obtain a freezing temperature of -20 degrees C. Field collected mosquitoes can be stored for up to 9 or more days in an ordinary thermos bottle by replacing the ice-salt mixture at 3-day intervals, without loss of enzyme activity. This method is a considerable improvement for the shipment of material from the field to the laboratory.

A new member of the Anopheles quadrimaculatus complex, species C.

A new member, species C, of the Anopheles quadrimaculatus complex was recently found in collections from the northwest coast of Florida. This new species cannot be differentiated from the other 2 species with available taxonomic keys. Evidence for this taxon as a sibling species includes data on hybrid sterility and distorted sex ratios in the progeny of crosses to species A and B, chromosomal differences, and diagnostic allozymes.

Multiple-technique identification of sibling species of the Anopheles quadrimaculatus complex.

In the past, most researchers used a single technique for identification of cryptic taxa, population structures, biosystematics, and phylogenetic studies. Our experience with the Anopheles quadrimaculatus complex shows the importance of using several methods on individual mosquitoes. This approach consists of analysis of the polytene chromosomes in ovarian nurse cells, gas chromatographic profiles of cuticular hydrocarbons, isozyme electrophoresis, and restriction site analysis of mitochondrial or genomic DNA. We recommend use of this multiple-technique approach when analyzing feral populations for the first time, or for correlating information obtained by investigators using different techniques.

Comparative susceptibility of species A, B and C of Anopheles quadrimaculatus complex to infection with subperiodic Brugia malayi and Brugia pahangi (Nematoda: Filarioidea).

Susceptibilities of natural populations of sibling species A, B and C of the Anopheles quadrimaculatus complex and the colonized strain A to subperiodic Brugia malayi and Brugia pahangi were compared. All 3 sibling species showed varying degrees of susceptibility to both B. pahangi and B. malayi, and they were considerably more susceptible to B. pahangi than to B. malayi. The rate and intensity of infection to B. pahangi were highest for species A (66.2% and 7.4 L3/female, respectively) and lowest for species B (21.3% and 1.7 L3/female). For B. malayi these values were higher for species A (29.7% and 1.84 L3/female) than for species B (13.3% and 0.86 L3/female) and C (12.6% and 0.75 L3/female). The colonized strain A of An. quadrimaculatus was significantly more susceptible to both Brugia species than the natural populations of sibling species A, B and C.

Diagnostic characterization of Anopheles freeborni and An. hermsi by hybrid crosses, frequencies of polytene X chromosomes and rDNA restriction enzyme fragments.

A polytene chromosome analysis was prepared from Anopheles freeborni collected from 25 locations in north and central California, and parts of Washington and Oregon. The X chromosome banding pattern, thought previously to be specific to An. hermsi, was common in mosquitoes collected from foothill regions in California, and in all samples from Washington and Oregon. At some of these locations, many mosquitoes had heterokaryotypes for the inversion that distinguishes the X chromosome of An. freeborni from that of An. hermsi. Use of rDNA restriction site analysis, and the results from crossing of different strains bearing either type of X chromosome, showed that An. hermsi does not have a unique or diagnostic X chromosome. Anopheles hermsi was collected in San Mateo County, CA, which is now the northernmost known limit of this species. Crossing studies, or the examination of rDNA restriction enzyme profiles, are presently the only means of identifying An. hermsi.

Primary congenital glaucoma clinical presentation and evaluation of modified trabeculectomy.

Primary congenital glaucoma is a relatively rare condition. A study on this subject to observe the mode of clinical presentation in our country and to evaluate the role of modified technique of trabeculectomy was undertaken. 30 eyes of 17 patients having primary congenital glaucoma were studies. The examination under general anaesthesia included (a) Anterior segment examination under operating microscope, (b) Corneal diameter measurement, (c) Fundus examination (d) IOP measurement and (e) Gonioscopy. The patients were subject to modified trabeculectomy operation. The assessment of the surgery was done during post-operative examination carefully. This paper includes an analysis of various clinical features of this condition. The observations revealed that the presenting symptoms are slightly different in our country compared to those in the developed countries. The overall success rate with our modified technique of trabeculectomy was 72.4 percent. Since most of our patients present with corneal opacity, we feel that modified trabeculectomy is a very effective surgical method for such cases.

Biotechnology and new integrated pest management approaches.

Area-wide pest management technologies will take on new appearances as the drive to eliminate and/or greatly reduce the use of chemical pesticides increases. The use of genetically altered insects has the most potential for successfully displacing certain pesticides, although the development of genetic engineering technologies for agricultural pest species is still in its infancy. Transformation vectors need to be developed as do transformation methodologies. Here we report the possibility of developing an interspecies vector and discuss ways in which such a vector could be used successfully in an integrated pest management system. If such an approach were developed, it could be utilized with other alternative methods, thereby providing a safe, ecologically sound means of controlling insect pests without damaging the agricultural economy.