The rare C9 P167S risk variant for age-related macular degeneration increases polymerization of the terminal component of the complement cascade.

Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma levels. Further analysis showed that patients with advanced AMD had elevated sC5b-9 compared to those with non-advanced AMD, although this was not associated with the P167S polymorphism. Electron microscopy of membrane attack complexes (MACs) generated using recombinantly produced wild type or P167S C9 demonstrated identical MAC ring structures. In functional assays, the P167S variant displayed a higher propensity to polymerize and a small increase in its ability to induce hemolysis of sheep erythrocytes when added to C9-depleted serum. The demonstration that this C9 P167S AMD risk polymorphism displays increased polymerization and functional activity provides a rationale for the gene therapy trials of sCD59 to inhibit the terminal pathway of complement in AMD that are underway.

Characterizing individual trainee learning curves in surgical training: Challenges and opportunities.

The surgical learning curve is an observable and measurable phenomenon. In the era of competency-based approaches to surgical training, monitoring the trajectory of individual trainee competence attainment could represent a meaningful method of formative and summative assessment. While technology can assist this approach, a number of significant barriers to the implementation of such assessment methods remain, including: accurate data collection, standard setting, and reliable assessment. Translating individual learning curve data into quantifiable case minimum targets in training poses further difficulties, and may not be possible for all procedures, particularly those that are less frequently performed and assessed. In spite of these challenges, significant benefits could be realized through an individualized approach to competency assessment using trainee learning curve data. Tracking competence acquisition against criterion-referenced standards could allow for targeted training and remediation, conforming with modern theories of adult education and empowering trainees to take control of their own learning. Learning curve data could also be used to assess the effects of educational interventions such as simulation-based training on subsequent competence acquisition rates. Ultimately, the individual learning curves of trainees could be used to inform personalised decisions regarding entrustment, credentialing, and certification, allowing training programmes to move beyond minimum operative experience targets as a crude proxy measure of competence.

Efferent limb stimulation prior to loop ileostomy closure: a systematic review and meta-analysis.

BACKGROUND: Postoperative ileus (POI) remains a common phenomenon following loop ileostomy closure. Our aim was to determine whether preoperative physiological stimulation (PPS) of the efferent limb reduced POI incidence. METHODS: A PRISMA-compliant meta-analysis searching PubMed, EMBASE and CENTRAL databases was performed. The last search was carried out on 30 January 2023. All randomized studies comparing PPS versus no stimulation were included. The primary endpoint was POI incidence. Secondary endpoints included the time to first passage of flatus/stool, time to resume oral diet, need for nasogastric tube (NGT) placement postoperatively, length of stay (LOS) and other complications. Random effects models were used to calculate pooled effect size estimates. Trial sequential analyses (TSA) were also performed. RESULTS: Three randomized studies capturing 235 patients (116 PPS, 119 no stimulation) were included. On random effects analysis, PPS was associated with a quicker time to resume oral diet (MD - 1.47 days, 95% CI - 2.75 to - 0.19, p = 0.02), shorter LOS (MD - 1.47 days, 95% CI - 2.47 to - 0.46, p = 0.004) (MD - 1.41 days, 95% CI - 2.32 to - 0.50, p = 0.002, I2 = 56%) and fewer other complications (OR 0.42, 95% CI 0.18 to 1.01, p = 0.05). However, there was no difference in POI incidence (OR 0.35, 95% CI 0.10 to 1.21, p = 0.10), the requirement for NGT placement (OR 0.50, 95% CI 0.21 to 1.20, p = 0.12) or time to first passage of flatus/stool (MD - 0.60 days, 95% CI - 1.95 to 0.76, p = 0.39). TSA revealed imprecise estimates for all outcomes (except LOS) and further studies are warranted to meet the required information threshold. CONCLUSIONS: PPS prior to stoma closure may reduce LOS and postoperative complications albeit without a demonstrable beneficial effect on POI. Further high-powered studies are required to confirm or refute these findings.

Early vs. standard reversal ileostomy: a systematic review and meta-analysis.

BACKGROUND: Formation of a defunctioning loop ileostomy is common after mid and low rectal resection. Historically, they were reversed between 3 and 6 months after initial resection. Recently, earlier closure (< 14 days) has been suggested by some current randomised controlled trials. The aim of this study was to investigate the effect of early stoma closure on surgical and patient outcomes. METHODS: A systematic review of the current randomised controlled trial literature comparing early and standard ileostomy closure after rectal surgery was performed. Specifically, we examined surgical outcomes including; morbidity, mortality and quality of life. RESULTS: Six studies met the predefined criteria and were included in our analysis. 275 patients underwent early stoma closure compared with 259 patients having standard closure. Overall morbidity was similar between both groups (25.5% vs. 21.6%) (OR, 1.47; 95% CI 0.75-2.87). However, there tended to be more reoperations (8.4 vs. 4.2%) (OR, 2.02, 95% CI 0.99-4.14) and small bowel obstructions/postoperative ileus (9.3% vs. 4.4%) (OR 0.44, 95% CI 0.22-0.90) in the early closure group, but no difference across the other domains. CONCLUSIONS: Early closure appears to be a feasible in highly selective cases after good perioperative counselling and shared decision-making. Further research on quality of life outcomes and long term benefits is necessary to help define which patients are suitable candidates for early closure.

Primary pneumococcal peritonitis can be the first presentation of a familial complement factor I deficiency1.

Primary pneumococcal peritonitis is a rare infection that has been described in women but has not been previously linked with immunodeficiency. The complement system plays a central role in immune defence against Streptococcus pneumoniae and, in order to evade complement attack, pneumococci have evolved a large number of mechanisms that limit complement-mediated opsonization and subsequent phagocytosis. We investigated an apparently immunocompetent woman with primary pneumococcal peritonitis and identified a family with deficiency for complement factor I. Primary pneumococcal peritonitis should be considered a possible primary immunodeficiency presentation.

Emergency laparotomy research methodology: A systematic review.

BACKGROUND: Emergency abdominal surgery is associated with poorer clinical outcomes than similar procedures in the elective setting. Research into emergency laparotomy (EL) care is moving from observational studies which simply measure EL outcomes to interventional research evaluating the implementation of care strategies designed to improve the quality and outcomes from EL care. There is no consensus as to the optimal approach to conducting research in this sphere. The primary objective of this review was to examine how mortality and other outcome measures were reported in previous EL research and to identify what might be the most appropriate methods in future outcome research. METHODS: A systematic review was performed in accordance with the PRISMA principles. Electronic databases were interrogated with a pre-specified search strategy to identify English language studies addressing outcomes from EL care. Retrieved papers were screened and assessed according to pre-defined eligibility criteria. The mortality and other outcomes reported in each paper were extracted and examined. RESULTS: 16 studies were included. They demonstrated significant heterogeneity in case definition, outcome reporting and data processing. A wide range of mortality and other outcome measures were applied and reported. Only few studies included on patient-reported outcomes measures. CONCLUSION: The heterogeneity in EL research, demonstrated by this review must be considered when EL outcomes are compared. A standardized approach with respect to case definition, outcome measurement, and data analysis would provide for more valid and comparable evaluation of EL outcomes. Future EL research should include more patient centred outcomes.

Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer.

BACKGROUND: The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long-course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6-8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. METHODS: A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8-week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence-free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta-analysis was performed using the Mantel-Haenszel method. RESULTS: Twenty-six publications, including four RCTs, with 25 445 patients were identified. A minimum 8-week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). CONCLUSION: A minimum 8-week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence-free survival without compromising surgical morbidity.

ANTECEDENTES: El tratamiento estándar actual del cáncer de recto localmente avanzado (locally advanced rectal cancer, LARC) consiste en quimiorradioterapia neoadyuvante de ciclo largo (neoadjuvant, long-course chemoradiation, nCRT) seguida de exéresis total del mesorrecto (total mesorectal excision, TME). De forma convencional, la cirugía se realiza a las 6-8 semanas después de la nCRT. Este estudio tuvo como objetivo determinar el efecto sobre los resultados de ampliar este intervalo. MÉTODOS: Se realizó una búsqueda sistemática de los estudios que analizaban los resultados oncológicos, comparando el intervalo clásico (< 8 semanas) desde el final de la nCRT hasta la TME con un intervalo mínimo de 8 semanas, en pacientes con LARC. El criterio de valoración principal fue la tasa de respuesta patológica completa (pathologic complete response, pCR). Los criterios de valoración secundarios fueron las tasas de supervivencia sin recidiva (recurrence-free survival, RFS), recidiva local (local recurrence, LR) y metástasis a distancia (distant metastasis, DM), tasas de resección R0, integridad (completeness) del mesorrecto, afectación del margen de resección, preservación esfinteriana, formación de estoma, fuga anastomótica y otras complicaciones. Se realizó un metaanálisis utilizando el método de Mantel-Haenszel. RESULTADOS: Se identificaron 26 publicaciones, incluidos cuatro ensayos clínicos aleatorizados, con 17.220 pacientes. Un intervalo mínimo de 8 semanas se asoció con un aumento de la razón de oportunidades (odds ratio, OR) de pCR (OR, 1,68, i.c. del 95% 1,37-2,06, P < 0,001) y de disminución del estadio tumoral (OR 1,18, i.c. del 95% 1,05-1,32, P = 0,004). Los porcentajes de resección R0, integridad del mesorrecto, ganglios linfáticos identificados, preservación esfinteriana, formación de estoma y complicaciones fueron similares entre los dos grupos. El aumento del porcentaje de pCR se tradujo en una disminución de las DM (OR 0,71, i.c. del 95% 0,54-0,93, P = 0,01) y de la recidiva global (OR 0,76, i.c. del 95% 0,58-0,98, P = 0,04), pero no de la LR (OR 0,83, i.c. del 95% 0,49-1,42, P = 0,50). CONCLUSIÓN: Un intervalo mínimo de 8 semanas entre el final de la nCRT y la TME aumenta las tasas de pCR y la reducción del estadio tumoral, así como mejora la RFS sin comprometer la morbilidad quirúrgica.

Close rectal dissection in benign diseases of the rectum: A review.

PURPOSE: Total mesorectal excision (TME) is the gold standard resectional strategy for rectal cancer to minimize loco-regional recurrence and optimize oncological outcomes. This plane is described by many as 'bloodless' but it does contain important pelvic neural plexuses and dissection may be close to the ureters and major vascular structures, particularly in inflammatory conditions of the distal colon and rectum. In such benign diseases a more conservative excision, so-called close rectal dissection, has been advocated to minimize damage to these structures. METHODS: A review of the literature was conducted to document the evolution of this procedure. Contemporary literature was interrogated to ascertain how this approach is adopted in minimally invasive surgery. Post-operative outcomes are compared to those from TME surgery. RESULTS: From early descriptions in 1956, this procedure has been adapted for use in laparoscopic surgery. It may be particularly useful in trans-anal mesorectal surgery. Reported benefits include reduced nerve injury and pelvic sepsis. However, this must be balanced against risks of mesorectal bleeding, rectal injury, and ongoing inflammation from the retained mesorectum. CONCLUSION: Rectal surgery in inflammatory conditions is technically challenging. Close rectal dissection is an alternate approach available to colorectal surgeons in these cases to minimize pelvic morbidity and optimize postoperative outcomes.

Exome arrays capture polygenic rare variant contributions to schizophrenia.

Schizophrenia is a highly heritable disorder. Genome-wide association studies based largely on common alleles have identified over 100 schizophrenia risk loci, but it is also evident from studies of copy number variants (CNVs) and from exome-sequencing studies that rare alleles are also involved. Full characterization of the contribution of rare alleles to the disorder awaits the deployment of sequencing technology in very large sample sizes, meanwhile, as an interim measure, exome arrays allow rare non-synonymous variants to be sampled at a fraction of the cost. In an analysis of exome array data from 13 688 individuals (5585 cases and 8103 controls) from the UK, we found that rare (minor allele frequency < 0.1%) variant association signal was enriched among genes that map to autosomal loci that are genome-wide significant (GWS) in common variant studies of schizophrenia genome-wide association study (PGWAS = 0.01) as well as gene sets known to be enriched for rare variants in sequencing studies (PRARE = 0.026). We also identified the gene-wise equivalent of GWS support for WDR88 (WD repeat-containing protein 88), a gene of unknown function (P = 6.5 × 10(-7)). Rare alleles represented on exome chip arrays contribute to the genetic architecture of schizophrenia, but as is the case for GWAS, very large studies are required to reveal additional susceptibility alleles for the disorder.

Schizophrenia genetics: emerging themes for a complex disorder.

After two decades of frustration, genetic studies of schizophrenia have entered an era of spectacular success. Advances in genotyping technologies and high throughput sequencing, increasing analytic rigour and collaborative efforts on a global scale have generated a profusion of new findings. The broad conclusions from these studies are threefold: (1) schizophrenia is a highly polygenic disorder with a complex array of contributing risk loci across the allelic frequency spectrum; (2) many psychiatric illnesses share risk genes and alleles, specifically, schizophrenia has substantial overlaps with bipolar disorder, intellectual disability, major depressive disorder and autism spectrum disorders; and (3) some convergent biological themes are emerging from studies of schizophrenia and related disorders. In this commentary, we focus on the very recent findings that have emerged in the past 12 months, and in particular, the areas of convergence that are beginning to emerge from multiple study designs.

A systematic review of the role of re-laparoscopy in the management of complications following laparoscopic colorectal surgery.

The benefits of laparoscopic versus open surgery for patients with both benign and malignant colorectal disease have been well established. Re-laparoscopy in patients who develop complications following laparoscopic colorectal surgery has recently been reported by some groups and the aim of this systematic review was to summarise this literature. A literature search of PubMed, Medline and EMBASE identified a total of 11 studies that reported laparoscopic re-intervention for complications in 187 patients following laparoscopic colorectal surgery. The majority of these patients required re-intervention in the immediate postoperative period (i.e. less than seven days). Anastomotic leakage was the commonest complication requiring re-laparoscopy reported (n = 139). Other complications included postoperative hernia (n = 12), bleeding (n = 9), adhesions (n = 7), small bowel obstruction (n = 4), colonic ischaemia (n = 4), bowel and ureteric injury (n = 3 respectively) and colocutaneous fistula (n = 1). Ninety-seven percent of patients (n = 182) who underwent re-laparoscopy had their complications successfully managed by re-laparoscopy, maintaining the benefits of the laparoscopic approach and avoiding a laparotomy. We conclude that re-laparoscopy for managing complications following laparoscopic colorectal surgery appears to be safe and effective in highly selected patients.

Copy number variants and therapeutic response to antidepressant medication in major depressive disorder.

It would be beneficial to find genetic predictors of antidepressant response to help personalise treatment of major depressive disorder (MDD). Rare copy number variants (CNVs) have been implicated in several psychiatric disorders, including MDD, but their role in antidepressant response has yet to be investigated. CNV data were available for 1565 individuals with MDD from the NEWMEDS (Novel Methods leading to New Medications in Depression and Schizophrenia) consortium with prospective data on treatment outcome with either a serotonergic or noradrenergic antidepressant. No association was seen between the presence of CNV (rare or common), the overall number of CNVs or genomic CNV 'burden' and antidepressant response. Specific CNVs were nominally associated with antidepressant response, including 15q13.3 duplications and exonic NRXN1 deletions. These were associated with poor response to antidepressants. Overall burden of CNVs is unlikely to contribute to personalising antidepressant treatment. Specific CNVs associated with antidepressant treatment require replication and further study to confirm their role in the therapeutic action of antidepressant.

The ENCODE project: implications for psychiatric genetics.

The ENCyclopedia Of DNA Elements (ENCODE) project is a public research consortium that aims to identify all functional elements of the human genome sequence. The project comprised 1640 data sets, from 147 different cell type and the findings were released in a coordinated set of 34 publications across several journals. The ENCODE publications report that 80.4% of the human genome displays some functionality. These data have important implications for interpreting results from large-scale genetics studies. We reviewed some of the key findings from the ENCODE publications and discuss how they can influence or inform further investigations into the genetic factors contributing to neuropsychiatric disorders.

Management of colorectal cancer in patients with inflammatory bowel disease.

BACKGROUND: This study evaluated the clinicopathological features and survival rates of patients with inflammatory bowel disease who developed colorectal cancer (CRC). METHODS: A retrospective review was performed on a prospectively maintained institutional database (1981-2011) to identify patients with inflammatory bowel disease who developed CRC. Clinicopathological parameters, management and outcomes were analysed. RESULTS: A total of 2,843 patients with inflammatory bowel disease were identified. One thousand six hundred and forty-two had ulcerative colitis (UC) and 1,201 had Crohn's disease (CD). Following exclusion criteria, there were 29 patients with biopsy-proven colorectal carcinoma, 22 of whom had UC and 7 had CD. Twenty-six patients had a preoperative diagnosis of malignancy/dysplasia; 16 of these were diagnosed at surveillance endoscopy. Nodal/distant metastasis was identified at presentation in 47 and 71 % of the UC and CD group, respectively. Operative morbidity for UC and CD was 33 and 17 %, respectively. Despite the less favourable operative outcomes following surgery management of UC-related CRC, overall 5-year survival was significantly better in the UC group compared to the CD group (41 vs. 29 %; p = 0.04) reflecting the difference in stage at presentation between the two groups. CONCLUSIONS: Patients who undergo surgery for UC-related CRC have less favourable short-term outcomes but present at a less advanced stage and have a more favourable long-term prognosis than similar patients with CRC and CD.

Complement factor I: Regulatory nexus, driver of immunopathology, and therapeutic.

Complement factor I (FI) is the nexus for classical, lectin and alternative pathway complement regulation. FI is an 88 kDa plasma protein that circulates in an inactive configuration until it forms a trimolecular complex with its cofactor and substrate whereupon a structural reorganization allows the catalytic triad to cleave its substrates, C3b and C4b. In keeping with its role as the master complement regulatory enzyme, deficiency has been linked to immunopathology. In the setting of complete FI deficiency, a consumptive C3 deficiency results in recurrent infections with encapsulated microorganisms. Aseptic cerebral inflammation and vasculitic presentations are also less commonly observed. Heterozygous mutations in the factor I gene (CFI) have been demonstrated to be enriched in atypical haemolytic uraemic syndrome, albeit with a very low penetrance. Haploinsufficiency of CFI has also been associated with decreased retinal thickness and is a strong risk factor for the development of age-related macular degeneration. Supplementation of FI using plasma purified or recombinant protein has long been postulated, however, technical difficulties prevented progression into clinical trials. It is only using gene therapy that CFI supplementation has reached the clinic with GT005 in phase I/II clinical trials for geographic atrophy.

Management of synchronous rectal and prostate cancer.

PURPOSE: Although well described, there is limited published data related to management on the coexistence of prostate and rectal cancer. The aim of this study was to describe a single institution's experience with this and propose a treatment algorithm based on the best available evidence. METHODS: From 2000 to 2011, a retrospective review of institutional databases was performed to identify patients with synchronous prostate and rectal cancers where the rectal cancer lay in the lower two thirds of the rectum. Operative and non-operative outcomes were analysed and a management algorithm is proposed. RESULTS: Twelve patients with prostate and rectal cancer were identified. Three were metachronous diagnoses (>3-month time interval) and nine were synchronous diagnoses. In the synchronous group, four had metastatic disease at presentation and were treated symptomatically, while five were treated with curative intent. Treatment included pelvic radiotherapy (74 Gy) followed by pelvic exenteration (three) and watchful waiting for rectal cancer (one). The remaining patient had a prostatectomy, long-course chemoradiotherapy and anterior resection. There were no operative mortalities and acceptable morbidity. Three remain alive with two patients disease-free. CONCLUSIONS: Synchronous detection of prostate cancer and cancer of the lower two thirds of the rectum is uncommon, but likely to increase with rigorous preoperative staging of rectal cancer and increased awareness of the potential for synchronous disease. Treatment must be individualized based on the stage of the individual cancers taking into account the options for both cancers including EBRT (both), surgery (both), hormonal therapy (prostate), surgery (both) and watchful waiting (both).

Association analysis of Notch pathway signalling genes in diabetic nephropathy.

AIMS/HYPOTHESIS: Several studies have provided compelling evidence implicating the Notch signalling pathway in diabetic nephropathy. Co-regulation of Notch signalling pathway genes with GREM1 has recently been demonstrated and several genes involved in the Notch pathway are differentially expressed in kidney biopsies from individuals with diabetic nephropathy. We assessed single-nucleotide polymorphisms (SNPs; n = 42) in four of these key genes (JAG1, HES1, NOTCH3 and ADAM10) for association with diabetic nephropathy using a case-control design. METHODS: Tag SNPs and potentially functional SNPs were genotyped using Sequenom or Taqman technologies in a total of 1371 individuals with type 1 diabetes (668 patients with nephropathy and 703 controls without nephropathy). Patients and controls were white and recruited from the UK and Ireland. Association analyses were performed using PLINK (http://pngu.mgh.harvard.edu/∼purcell/plink/) and haplotype frequencies in patients and controls were compared. Adjustment for multiple testing was performed by permutation testing. RESULTS: In analyses stratified by centre, we identified six SNPs, rs8708 and rs11699674 (JAG1), rs10423702 and rs1548555 (NOTCH3), rs2054096 and rs8027998 (ADAM10) as being associated with diabetic nephropathy before, but not after, adjustment for multiple testing. Haplotype and subgroup analysis according to duration of diabetes also failed to find an association with diabetic nephropathy. CONCLUSIONS/INTERPRETATION: Our results suggest that common variants in JAG1, HES1, NOTCH3 and ADAM10 are not strongly associated with diabetic nephropathy in type 1 diabetes among white individuals. Our findings, however, cannot entirely exclude these genes from involvement in the pathogenesis of diabetic nephropathy.

Treatment of multiple sclerosis with T-cell receptor peptides: results of a double-blind pilot trial.

A T-cell receptor (TCR) peptide vaccine from the V beta 5.2 sequence expressed in multiple sclerosis (MS) plaques and on myelin basic protein (MBP)-specific T cells boosted peptide-reactive T cells in patients with progressive MS. Vaccine responders had a reduced MBP response and remained clinically stable without side effects during one year of therapy, whereas nonresponders had an increased MBP response and progressed clinically. Peptide-specific T helper 2 cells directly inhibited MBP-specific T helper 1 cells in vitro through the release of interleukin-10, implicating a bystander suppression mechanism that holds promise for treatment of MS and other autoimmune diseases.

Excision and primary closure using the Karydakis flap for the treatment of pilonidal disease: outcomes from a single institution.

BACKGROUND: Chronic pilonidal disease is a debilitating condition that typically affects young adults. There is a wide variety of available therapeutic strategies reflecting the inconsistent outcomes attributed to the various operative approaches. The majority involve excision of the sinus tract followed by either primary closure or healing by secondary intention. A variety of closure approaches exist. There remains uncertainty as to which is more effective. The aim of the current study was to determine subjective and objective outcomes following excision and Karydakis flap closure in a unit where this technique is the standard of care in the management of chronic pilonidal disease. METHODS: This study involving consecutive patients with chronic pilonidal disease was conducted over a 4-year period. A tailored patient satisfaction questionnaire was given to each patient. Postoperative primary and secondary outcomes were evaluated. The mean follow-up time was 30 months. RESULTS: One hundred six consecutive patients (33 female, 73 male) underwent excision and primary closure using the Karydakis flap. Ninety-two completed questionnaires were returned (87% response rate). Patients consulted their general practitioner 2.8 times (mean) and 46% received empirical oral antimicrobial therapy prior to referral for a surgical opinion. The mean time lost to work/school following the Karydakis flap repair was 13 days (range 3-33). Successful treatment was achieved in 96.3% of cases and 92% of patients were satisfied with their operative result. CONCLUSION: Excision and primary closure with Karydakis flap is an effective treatment for chronic pilonidal disease. It is associated with low morbidity, early return to premorbid functioning, and a high degree of patient satisfaction (92%).