Determinants of 30-d readmission after colectomy.

BACKGROUND: Readmission after colectomy has become an important metric for measuring quality of care. Our aim was to investigate the impact of patient and hospital characteristics on 30-d readmission rates among patients undergoing colectomies in Pennsylvania. METHODS: Data were obtained from the Pennsylvania Health Care Cost Containment Council, which included all patients undergoing colectomy during 2011 (n = 10,155). Characteristics of non-readmitted and readmitted patients were compared with univariate tests. The primary outcome was 30-d readmission, which was modeled using multivariable logistic regression. RESULTS: Of the 10,155 patients who underwent colectomy, 1492 (14.7%) were readmitted within 30 d of discharge. Readmission was influenced by the underlying diagnosis (P < 0.001). Additionally, readmission was more likely with a Charlson comorbidity index ≥ 2 (odds ratio [OR] = 1.57, P < 0.001), emergent admission (OR = 1.26, P = 0.001), an in-hospital complication (OR = 1.46, P < 0.001), lowest quartile for surgeon volume (OR = 1.24, P = 0.01), and construction of an ileostomy (OR = 2.31, P < 0.001). Factors associated with decreased likelihood of readmission included laparoscopic surgery (OR = 0.73, P < 0.001). No association with hospital volume was found. CONCLUSIONS: A 30-d readmission after colectomy is influenced by numerous patient- and surgeon-related factors. Reducing in-hospital complications, and improving patient education after ileostomy construction, provide substantial targets for intervention. Our data also suggest that there may be a critical range of colectomies performed annually by surgeons, greater than which no additional benefit is conferred in reducing readmissions, but below which there is an increased risk of readmission. Further research is needed to determine the influence of laparoscopic surgery in reducing readmission in equally matched patient populations.

Phage tail-like particles kill Clostridium difficile and represent an alternative to conventional antibiotics.

BACKGROUND: Current Clostridium difficile infection (CDI) antibiotic regimens have become increasingly ineffective at achieving cure and preventing recurrence. A recently developed alternative to conventional antibiotics are phage tail-like particles (PTLPs), which are proteins that are morphologically similar to bacteriophages and are produced by C difficile. This study examines the in vitro killing spectrum of a previously unreported PTLP isolated from a clinical isolate of C difficile. METHODS: Using patient-derived samples from an institutional review board-approved C difficile tissue bank, a ribotype 078 C difficile isolate was anaerobically incubated on blood agar plates that were preswabbed with norfloxacin to induce the production of PTLPs. Concentrated PTLP populations were confirmed using transmission electron microscopy. Using a standard lawn spot approach, bactericidal activity was assessed as indicated by a clearing within the bacterial lawn. The PTLP genomic cluster was also fully sequenced and open reading frames were annotated according to predicted function. RESULTS: PTLPs were assessed using 64 patient-derived C difficile isolates of varying ribotypes. PTLPs demonstrated complete bactericidal activity in 21 of 25 ribotype 027 isolates with partial activity in 2 of the 25. Complete bactericidal activity was not demonstrated against any other ribotype or non-difficile bacteria, suggesting a species and ribotype specificity. Functional genes, which may be necessary for killing, were identified within the PTLP genetic locus. CONCLUSION: PTLPs demonstrate capability in eradicating C difficile in vitro, and with further development, may represent an organism-specific, microbiome-sparing therapy for CDI.

An interleukin-4 polymorphism is associated with susceptibility to Clostridium difficile infection in patients with inflammatory bowel disease: results of a retrospective cohort study.

BACKGROUND: Clinical studies have suggested that patients with inflammatory bowel disease (IBD) are at greater risk for developing Clostridium difficile infection (CDI). The purpose of this study was to identify single-nucleotide polymorphisms (SNPs) associated with CDI among IBD patients. METHODS: This retrospective cohort study used our biobank to compare patients with IBD who developed CDI (IBD-CDI) with those who had never contracted CDI (IBD-nCDI). Patients were genotyped for 384 IBD-associated SNPs by microarray. Student t, chi-square, and Fisher exact tests were used. Multivariate logistic regression with Bonferroni correction was used for genotype analysis. RESULTS: Twenty IBD-CDI (14 with Crohn disease; 6 with ulcerative colitis) and 152 IBD-nCDI (47 CD/105 UC) patients were identified. The interleukin-4-associated SNP rs2243250 was associated with the development of CDI (raw P = .00005/corrected P = .02), with 15 of 20 (75%) CDI-IBD patients harboring the at-risk "A" allele versus 52 of 152 (34%) of IBD-nCDI. When we compared Crohn disease and ulcerative colitis patients separately, rs2243250 initially was associated with CDI in both groups, although clinical relevance was lost after Bonferroni correction. CONCLUSION: The interleukin-4 gene-associated SNP rs2243250 was strongly associated with CDI in our IBD population. This SNP may allow for the identification of IBD patients at greater risk for CDI.

Proton pump inhibitors induce changes in colonocyte gene expression that may affect Clostridium difficile infection.

BACKGROUND: Proton pump inhibitors seem to promote Clostridium difficile infection (CDI). Although the current literature suggests that this association is mediated through gastric acid suppression, there has been little investigation into whether a direct effect on expression of colonocyte genes may also have a role. The aim of this study was to investigate the effect of omeprazole on genome-wide gene expression in a human colonic cell line. METHODS: T84 cell monolayers were treated with acid-activated omeprazole at 0, 1, 10, or 100 µmol/L for 48 hours. Cells were lysed and total RNA samples were reverse transcribed and used to generate biotinylated cRNA. Whole-genome transcript expression levels were then quantified using an Illumina HT-12 BeadChip microarray targeting 25,440 genes. Transcripts with a stringent minimum absolute fold change of 1.5 and an adjusted nominal P value <.05 (false discovery) were identified as being differentially expressed. RESULTS: Significant changes in expression were observed for 322 colonocyte transcripts, including genes with potential implications for susceptibility to CDI. These genes include roles in cell junctions, toxin susceptibility, and bile acid metabolism and transport. CONCLUSION: Omeprazole treatment decreases the expression of genes that have important functions in colonocyte integrity. Such impairment in colonocyte function may promote CDI.

Ulcerative colitis neoplasia is not associated with common inflammatory bowel disease single-nucleotide polymorphisms.

BACKGROUND: Neoplasia complicating ulcerative colitis (UC-neoplasia) is a problem that is poorly addressed by present surveillance techniques. The association of greater than 300 single nucleotide polymorphisms (SNPs) with inflammatory bowel disease (IBD) suggests the possibility that certain genetic polymorphisms might identify patients with UC destined for malignant degeneration. This present study tested the hypothesis that presently known IBD-associated SNPs may correlate with UC-neoplasia. MATERIALS AND METHODS: A total of 41 patients with UC-neoplasia (mean age 56 ± 2.1 years) were identified from our divisional IBD Biobank (low-grade dysplasia n = 13, high-grade dysplasia n = 8, colorectal cancer [CRC] n = 20). These patients were individually age, sex, and disease duration matched with UC patients without neoplasia. Primary sclerosing cholangitis and family history of CRC were recorded. Patients were genotyped for 314 of the most commonly IBD-associated SNPs by a custom SNP microarray. Logistic regression and Fischer exact test were used for statistical analysis. RESULTS: After Bonferroni correction, none of the 314 IBD-associated SNPs correlated with UC-neoplasia when compared with matched UC controls. The incidence of primary sclerosing cholangitis was greater in the UC-neoplasia group (10/41, 24% vs 3/41, 7%; P = .03) compared with UC controls. The severity of neoplasia (low grade dysplasia versus high grade dysplasia versus CRC) correlated with disease duration (7.9 vs 13.4 vs 20.7 years, respectively). CONCLUSION: The lack of correlation between well-known IBD-associated SNPs and UC-neoplasia demonstrated in this study suggests that the development of neoplasia in patients with UC is associated with genetic determinants other than those that predispose to inflammation or results from posttranslational modifications or epigenetic factors rather than germline polymorphisms.

Increased risk of incisional hernia after sigmoid colectomy for diverticulitis compared with colon cancer.

BACKGROUND: We aimed to determine if an increased incidence of incisional hernias is present in patients undergoing sigmoidectomy for diverticulitis vs cancer. The pathophysiology of diverticulitis is poorly understood, but might involve a collagen vascular abnormality that can predispose to incisional hernia. STUDY DESIGN: In this IRB-approved, retrospective study, patients who underwent sigmoid colectomies for diverticulitis or cancer between January 2003 and September 2012 were studied. Exclusion criteria included the development of surgical site infections and neoadjuvant chemoradiotherapy. A multivariate logistic regression was used with covariate adjustments for known risk factors for hernia development. RESULTS: Four hundred forty-two patients (mean age 59.3 ± 13.9 years) with a median follow-up of 30 months were analyzed. The incidence of incisional hernia was 15.1% in diverticulitis patients vs 5.8% in the cancer cohort (41 of 271 vs 10 of 171; p = 0.003). Univariate analysis of risk factors associated with postoperative incisional hernia included steroid use (p = 0.007), wound packing (p = 0.001), higher American Society of Anesthesiologists classification (p = 0.001), absorbable suture closure (p = 0.02), blood transfusion (p = 0.04), stoma formation (p = 0.02), increased body mass index (p = 0.008), and history of incisional hernia (p = 0.00008). Multivariate logistic regression demonstrated a persistent association between diverticulitis and hernia development (p = 0.01). Odds of a hernia developing after sigmoidectomy for diverticulitis were 2.82 times greater than in the cancer cohort (95% CI, 1.3-6.6). CONCLUSIONS: The incidence of an incisional hernia developing after a sigmoid colectomy is significantly higher when performed for diverticulitis as compared with cancer. This might be due to a connective tissue disorder, which predisposes to development of both diverticula and hernias.

Single nucleotide polymorphisms of the tcdC gene and presence of the binary toxin gene predict recurrent episodes of Clostridium difficile infection.

OBJECTIVE: To identify Clostridium difficile genotypes, which are associated with recurrent C difficile infection (RCDI). BACKGROUND: Reliable bacterial genetic factors predicting RCDI are currently lacking. METHODS: Inpatients and outpatients 18 years or older treated at our institution for C difficile infection (CDI) of any severity were consecutively enrolled. CDI was defined as symptoms of colitis with a positive PCR stool test. Each bacterial isolate was studied for virulence factors: tcdC mutations, including single nucleotide polymorphisms (SNPs) via PCR, the presence of genes for toxins A, B and binary toxin using restriction fragment length polymorphism, and identification of ribotype by PCR. χ tests, t tests, and logistic and linear regression were used to determine which virulence factors predicted RCDI and the need for hospital admission, with corrections made for multiple statistical comparisons. RESULTS: Seventy-three patients (male: 52%; mean age: 66 ± 15 years) were studied. Binary toxin gene (P = 0.03) was associated with at least 1 episode of RCDI, as was the presence of SNPs C184T (P = 0.006) and A117T (P = 0.003). The presence of the binary toxin gene with either of these tcdC SNPs increased RCDI by 80% (P = 0.0002) but did not predict the need for hospital admission. None of the other virulence factors, including ribotype 027, were predictive of RCDI. CONCLUSIONS: The presence of the binary toxin gene and tcdC SNPs C184T and A117T strongly predict RCDI. The presence of both tcdC SNPs and the binary toxin gene significantly increased the risk of RCDI, which might warrant longer antibiotic courses to eradicate the infection.

Former optimism: present pessimism: will the tide turn? - abstract

Conceived in the darkest days of World War Two, the University of the West Indies was born into a post-war world in which the past suffering and current hardship were more than matched by hope. Hope for a more compassionate society, more just, more free. Great men gave the UCWI its special character. Taylor, Springer, Sherlock, Swaby and many more, until it became, in its own right, one of the world's great universities. Today the world spends a trillion dollars every year on armaments, yet a billion people live in poverty. Fifty thousand nuclear warheads lie in hiding, waiting for some mistake to unleash them to destroy the planet, already dying slowly from the syndrome of pollution, soil erosion, deforestation and ozone depletion. An outmoded international economic system daily increases the wealth of the rich and the debts of the poor. Yet there is hope. While the vision is remembered it may be rekindled. The medical profession can and must cast aside its myopia and take the lead (AU)

Some features of the obstetrical performance of primigravidae - abstract

Four hundred and seven primigravidae with single pregnancies were delivered in the University College Hospital of the West Indies July 1953 to December 1954, inclusive. In reviewing these cases punch cards are used. The following points are made:- (1) Age distribution: Forty per cent of these primigravidae were under the age of 20, as compared to only 12 percent of a comparable series in Scotland. (2) Difficult labour: The occurence of true difficult labour (about 20 percent) is just about the same as in the Scottish series, despite differences in age distribution, nutrition, economic status and race. In both series, the incidence of difficult labour increases with age and with prolongation of pregnancy past term. Perineal tears and episiotomies are less in the Jamaican cases of all age groups. (3) Toxaemia: The occurence of both mild and severe pre-eclampsia is about half that in the Scottish series, but eclampsia is three times more common. (4) Prematurity: 13.8 percent of babies were premature by weight (5 1/2 pounds or less) as compared to 6.5 percent in a British series. Despite this the combined stillbirth and neonatal death rate was the same as in the Scottish group - 4.2 percent. (5) Lactation: Ninety-five per cent of surviving babies left hospital fully breast fed; 83 percent were still fully breast fed when seen at the postnatal clinic six weeks after birth. Plans for further investigations are mentioned (AU)

Autotransfusion in ruptured ectopic pregnancy

In a fourteen year period 1055 cases of ruptured ectopic pregnancy were operated on at one hospital in the West Indes. 76 percent of these patients required transfusion, and 530 were given their own blood collected from the intraperitoneal cavity, with or without donor blood. In 424 other cases the blood collected in this way was unsuitable for autotransfusion. On blood culture only "air contaminants" were found. There were only two complications (fever in one case and hypotension in another) and no deaths related to transfusion. In view of the hazards of transfusion of donor blood and the shortage of such blood in many centres, a plea is made for the reintroduction of this procedure in the management of ruptured ectopic pregnancies (AU)

Specialist training in obstetrics and gynaecology. 5th Grabham Oration delivered at the University of the West Indies, October 1967

One of the many privileges of the Presidency of the Grabham Society is the opportunity to give one sermon-like oration, free from the risk of immediate contradiction. If this engenders subsequent discussion and argument it will have fulfilled its function. To sum it up:- Whatever decisions are made about postgraduate training in obstetrics and gynaecology must be designed to meet the needs of our patients, our Caribbean communities, and our students here and now. We must not become too preoccupied with detailed planning for the distant and unpredictable future. Our task is two-fold: to improve the obstetrics and gynaecological services in our communities and to train to a high standard the young men and women who will soon be running them. We can rightly be critical of much that is wrong with the present state of affairs, but criticism is useful only as a guide to action and not as an end in itself. The postgraduate training programme in the West Indies must be developed to meet our own needs and should establish a standard which is second to none. National or regional higher qualifications are of secondary importance and can be evolved later on when the need arises. After all, the present is only a phase in evolution, a moment in history. As that great scholar and obstetrician William Smellie (1762) wisely wrote, "in order that the young practitioner may not be misled by the useless theories and uncertain conjectures of both ancient and modern writers, it may be necessary to observe in general, that all the hypotheses hitherto espoused are liable to many material objections; and that almost every system hath been overthrown by that which followed it". This is true of Obstetrics and Gynaecology, and even more so of the broader field of medical education (AU)

Unorthodox repair of a vesico-cervical fistula

A vesico-cervical fistula caused by a difficult labour and delivery was complicated by post-inflammatory fibrosis of the paracervical tissues and by urethral damage following lymphogranuloma venerum. The fistula was approached by splitting the cervical stump after a subtotal hysterectomy, and then closed successfully. The technique may be useful to others who encounter such unusual problems.