Genome-wide copy number variation study in anorectal malformations

Anorectal malformations (ARMs, congenital obstruction of the anal opening) are among the most common birth defects requiring surgical treatment (2-5/10 000 live-births) and carry significant chronic morbidity. ARMs present either as isolated or as part of the phenotypic spectrum of some chromosomal abnormalities or monogenic syndromes. The etiology is unknown. To assess the genetic contribution to ARMs, we investigated single-nucleotide polymorphisms and copy number variations (CNVs) at genome-wide scale. A total of 363 Han Chinese sporadic ARM patients and 4006 Han Chinese controls were included. Overall, we detected a 1.3-fold significant excess of rare CNVs in patients. Stratification of patients by presence/absence of other congenital anomalies showed that while syndromic ARM patients carried significantly longer rare duplications than controls (P = 0.049), non-syndromic patients were enriched with both rare deletions and duplications when compared with controls (P = 0.00031). Twelve chromosomal aberrations and 114 rare CNVs were observed in patients but not in 868 controls nor 11 943 healthy individuals from the Database of Genomic Variants. Importantly, these aberrations were observed in isolated ARM patients. Gene-based analysis revealed 79 genes interfered by CNVs in patients only. In particular, we identified a de novo DKK4 duplication. DKK4 is a member of the WNT signaling pathway which is involved in the development of the anorectal region. In mice, Wnt disruption results in ARMs. Our data suggest a role for rare CNVs not only in syndromic but also in isolated ARM patients and provide a list of plausible candidate genes for the disorder.postprin

Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis

Christine SM Lau,1,2 Ronald S Chamberlain1–3 1Department of Surgery, Saint Barnabas Medical Center, Livingston, NJ, USA; 2Saint George's University School of Medicine, Grenada, West Indies; 3Department of Surgery, New Jersey Medical School, Rutgers University, Newark, NJ, USA Introduction: Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea. CDI has increased in incidence and severity over the past decade, and is a growing worldwide health problem associated with substantial health care costs and significant morbidity and mortality. This meta-analysis examines the impact of probiotics on the incidence of Clostridium difficile-associated diarrhea (CDAD) among children and adults, in both hospital and outpatient settings. Methods: A comprehensive literature search of all published randomized control trials (RCTs) assessing the use of probiotics in the prevention of CDAD in patients receiving antibiotic therapy was conducted, and the incidence of CDAD was analyzed. Results: Twenty-six RCTs involving 7,957 patients were analyzed. Probiotic use significantly reduced the risk of developing CDAD by 60.5% (relative risk [RR] =0.395; 95% confidence interval [CI], 0.294–0.531; P<0.001). Probiotics proved beneficial in both adults and children (59.5% and 65.9% reduction), especially among hospitalized patients. Lactobacillus, Saccharomyces, and a mixture of probiotics were all beneficial in reducing the risk of developing CDAD (63.7%, 58.5%, and 58.2% reduction). Conclusion: Probiotic supplementation is associated with a significant reduction in the risk of developing CDAD in patients receiving antibiotics. Additional studies are required to determine the optimal dose and strain of probiotic. Keywords: probiotics, Clostridium difficile-associated diarrhea, antibiotic-associated diarrhe

Probiotics improve the efficacy of standard triple therapy in the eradication of Helicobacter pylori: a meta-analysis

Christine S M Lau,1,2 Amanda Ward,2 Ronald S Chamberlain1–4 1Department of Surgery, Saint Barnabas Medical Center, Livingston, NJ, USA; 2Saint George’s University School of Medicine, Grenada, West Indies; 3Department of Surgery, Banner MD Anderson Cancer Center, Gilbert, AZ, USA; 4Department of Surgery, New Jersey Medical School, Rutgers University, Newark, NJ, USA Introduction: Helicobacter pylori colonization is present in half of the world’s population and can lead to numerous gastrointestinal diseases if left untreated, including peptic ulcer disease and gastric cancer. Although concurrent triple therapy remains the recommended treatment regimen for H. pylori eradication, its success rate and efficacy have been declining. Recent studies have shown that the addition of probiotics can significantly increase eradication rates by up to 50%. This meta-analysis examines the impact of probiotic supplementation on the efficacy of standard triple therapy in eradicating H. pylori. Methods: A comprehensive literature search was conducted using PubMed, Cochrane Central Registry of Controlled Trials, and Google Scholar (time of inception to 2016) to identify all published randomized control trials (RCTs) assessing the use of probiotics in addition to triple therapy for the treatment of H. pylori. Searches were conducted using the keywords “probiotics”, “triple therapy”, and “Helicobacter pylori”. RCTs comparing the use of probiotics and standard triple therapy with standard triple therapy alone for any duration in patients of any age diagnosed with H. pylori infection were included. H. pylori eradication rates (detected using urea breath test or stool antigen) were analyzed as-per-protocol (APP) and intention-to-treat (ITT). Results: A total of 30 RCTs involving 4,302 patients APP and 4,515 patients ITT were analyzed. The addition of probiotics significantly increased eradication rates by 12.2% (relative risk [RR] =1.122; 95% confidence interval [CI], 1.091–1.153; P<0.001) APP and 14.1% (RR =1.141; 95% CI, 1.106–1.175; P<0.001) ITT. Probiotics were beneficial among children and adults, as well as Asians and non-Asians. No significant difference was observed in efficacy between the various types of probiotics. The risk of diarrhea, nausea, vomiting, and epigastric pain was also reduced. Conclusion: The addition of probiotics is associated with improved H. pylori eradication rates in both children and adults, as well as Asians and non-Asians. Lactobacillus, Bifidobacterium, Saccharomyces, and mixtures of probiotics appear beneficial in H. pylori eradication. Furthermore, the reduction in antibiotic-associated side effects such as nausea, vomiting, diarrhea, and epigastric pain improves medication tolerance and patient compliance. Given the consequences associated with chronic H. pylori infection, the addition of probiotics to the concurrent triple therapy regimen should be considered in all patients with H. pylori infection. However, further studies are required to identify the optimal probiotic species and dose. Keywords: probiotics, Helicobacter pylori, triple therapy, meta-analysi

Use of preoperative gabapentin significantly reduces postoperative opioid consumption: a meta-analysis

Sudha Arumugam,1 Christine SM Lau,1,2 Ronald S Chamberlain1–3 1Department of Surgery, Saint Barnabas Medical Center, Livingston, NJ, USA; 2Saint George’s University School of Medicine, Grenada, West Indies; 3Department of Surgery, Rutgers University, New Jersey Medical School, Newark, NJ, USA Objectives: Effective postoperative pain management is crucial in the care of surgical patients. Opioids, which are commonly used in managing postoperative pain, have a potential for tolerance and addiction, along with sedating side effects. Gabapentin’s use as a multimodal analgesic regimen to treat neuropathic pain has been documented as having favorable side effects. This meta-analysis examined the use of preoperative gabapentin and its impact on postoperative opioid consumption.Materials and methods: A comprehensive literature search was conducted to identify randomized control trials that evaluated preoperative gabapentin on postoperative opioid consumption. The outcomes of interest were cumulative opioid consumption following the surgery and the incidence of vomiting, somnolence, and nausea.Results: A total of 1,793 patients involved in 17 randomized control trials formed the final analysis for this study. Postoperative opioid consumption was reduced when using gabapentin within the initial 24 hours following surgery (standard mean difference -1.35, 95% confidence interval [CI]: -1.96 to -0.73; P<0.001). There was a significant reduction in morphine, fentanyl, and tramadol consumption (P<0.05). While a significant increase in postoperative somnolence incidence was observed (relative risk 1.30, 95% CI: 1.10–1.54, P<0.05), there were no significant effects on postoperative vomiting and nausea.Conclusion: The administration of preoperative gabapentin reduced the consumption of opioids during the initial 24 hours following surgery. The reduction in postoperative opioids with preoperative gabapentin increased postoperative somnolence, but no significant differences were observed in nausea and vomiting incidences. The results from this study demonstrate that gabapentin is more beneficial in mastectomy and spinal, abdominal, and thyroid surgeries. Gabapentin is an effective analgesic adjunct, and clinicians should consider its use in multimodal treatment plans among patients undergoing elective surgery. Keywords: gabapentin, preemptive analgesia, opioid, postoperative pai

Trends in incidence, survival, and management of uveal melanoma: a population-based study of 7,516 patients from the Surveillance, Epidemiology, and End Results database (1973–2012)

Krishnaraj Mahendraraj,1 Christine SM Lau,1,2 Injoon Lee,2 Ronald S Chamberlain1–3 1Department of Surgery, Saint Barnabas Medical Center, Livingston, NJ, USA; 2St George’s University School of Medicine, Grenada, West Indies; 3Department of Surgery, New Jersey Medical School, Rutgers University, Newark, NJ, USA Introduction: Uveal melanoma (UM) is the most common primary intraocular malignancy, despite comprising <5% of all melanomas. To date, relatively few case series of UM have been published. Moreover, the factors influencing survival remain largely unknown. This study sought to analyze the impact of demographics, histology, clinical presentation, and treatments on the clinical outcomes of UM in a large modern nationwide patient cohort.Methods: Demographics and clinical data were abstracted on 277,120 histologically confirmed melanoma patients from the Surveillance, Epidemiology, and End Results database between 1973 and 2012.Results: A total of 7,516 cases of UM represented 3.2% of all recorded cases of melanoma. The mean age-adjusted incidence was 5.1 per million (95% CI 4.2–6.1) and was higher in males (5.9, CI =4.4–7.6) compared to females (4.5, CI =3.3–5.8), P<0.001. UM occurred most commonly in the sixth decade of life (61.4±15) and among Caucasians (94.7%). A total of 52.3% of cases were reported in the Western US (35.7% in California). The initial diagnoses in 65.2% of cases were by histopathology, followed by clinical diagnosis (18.8%) and radiographic imaging (16.0%). The percentage of UM cases managed by surgery alone decreased by 69.4% between the 1973–1977 and 2006–2012 time periods, concomitant with a 62% increase in primary radiotherapy, P<0.001. The UM mean overall and cancer-specific 5-year relative survival rates were 79.8%±5.8% and 76%±5.3%, respectively. The mean 5-year cancer-specific survival rate (76%) remained stable during the study period between 1973 and 2012. The mean survival for patients treated with primary radiotherapy was significantly improved compared to those treated with surgery alone (15.4±0.4 vs 13.6±0.3, P<0.001). Multivariate analysis identified male sex (odds ratio [OR] 1.1, CI =1.0–1.3), age >50 years (OR 4.0, CI =3.4–4.6), distant metastases (OR 8.6, CI =4.7–15), and primary surgical treatment (OR 2.6, CI =2.0–3.3) as independently associated with increased mortality, P<0.005. Conversely, patients identified as Hispanic (OR 0.6, CI =0.5–0.8) and patients receiving radiation treatment (OR 0.5, CI =0.4–0.7) were independently associated with reduced mortality, P<0.005.Conclusion: UM remains a rare form of melanoma that occurs primarily in Caucasian patients older than 50 years. More than two-thirds of UM patients are curatively treated with primary radiotherapy as opposed to surgery, which has resulted in a significant improvement in both overall survival and cancer-specific survival. Despite this shift in management strategy, the mean 5-year cancer-specific survival rate remained relatively unchanged during the study period. Male sex, older age, distant disease, and primary surgical therapy rather than radiotherapy are associated with an increased risk of mortality. Keywords: uveal melanoma, ocular melanoma, SEER&nbsp

Ocular melanoma-when you have seen one, you have not seen them all: a clinical outcome study from the Surveillance, Epidemiology and End Results (SEER) database (1973–2012)

Krishnaraj Mahendraraj,1 Sneha Shrestha,1 Christine SM Lau,1,2 Ronald S Chamberlain1–4 1Department of Surgery, Saint Barnabas Medical Center, Livingston, NJ, USA; 2Saint George’s University School of Medicine, Grenada, West Indies; 3Department of Surgery, Banner MD Anderson Cancer Center, Gilbert, AZ, USA; 4Department of Surgery, Rutgers University, New Jersey Medical School, Newark, NJ, USA Background: Ocular melanoma (OM) comprises <5% of all melanomas. Uveal melanoma (UM) is the most common subtype of OM, while conjunctival melanoma (CM) is rare and differs significantly from UM. The purpose of this study is to evaluate a large cohort of OM patients to differentiate demographic, pathologic, and clinical factors between these two neoplasms, which may affect treatment and outcomes. Methods: The Surveillance, Epidemiology, and End Results database (1973–2012) was used to extract demographic and clinical data on 8,165 OM patients (92.1% UM and 7.9% CM). Results: Both CM and UM were most prevalent among Caucasian males in the seventh decade of life. UM patients presented more often with localized disease (90.9% vs 81.2, P<0.01). Surgery (42.8%), radiation (43.0%), or combined surgery and radiation (7.0%) were used in the treatment of UM, while CM was treated almost exclusively with surgery (88.7%). Mean overall survival was longer (15.4 vs 14.6 years; P<0.01) and mortality rates were lower in patients (38.8% vs 46.1%; P<0.01) with CM. Conclusion: Despite presenting with more advanced disease than UM, CM is associated with an increased overall survival. Surgery is the primary therapy for CM, whereas radiotherapy is the primary therapy for UM and is associated with prolonged survival. Keywords: ocular melanoma, uveal melanoma, conjunctival melanoma, SEE

Determining 30-day readmission risk for heart failure patients: the Readmission After Heart Failure scale

Ronald S Chamberlain,1–5 Jaswinder Sond,1 Krishnaraj Mahendraraj,1 Christine SM Lau,1,3 Brianna L Siracuse1 1Department of Surgery, Saint Barnabas Medical Center, Livingston, 2Department of Surgery, Rutgers New Jersey Medical School, Rutgers University, Newark, NJ, USA; 3St. George’s University School of Medicine, Grenada, West Indies; 4Department of Surgery, Banner MD Anderson Cancer Center, Gilbert, AZ, USA; 5Department of Surgery, Valley Cancer Surgical Specialists, Phoenix, AZ, USA Background: Chronic heart failure (CHF), which affects >5 million Americans, accounts for >1 million hospitalizations annually. As a part of the Hospital Readmission Reduction Program, the Affordable Care Act requires that the Centers for Medicare and Medicaid Services reduce payments to hospitals with excess readmissions. This study sought to develop a scale that reliably predicts readmission rates among patients with CHF. Methods: The State Inpatient Database (2006–2011) was utilized, and discharge data including demographic and clinical characteristics on 642,448 patients with CHF from California and New York (derivation cohort) and 365,359 patients with CHF from Florida and Washington (validation cohort) were extracted. The Readmission After Heart Failure (RAHF) scale was developed to predict readmission risk.Results: The 30-day readmission rates were 9.42 and 9.17% (derivation and validation cohorts, respectively). Age <65 years, male gender, first income quartile, African American race, race other than African American or Caucasian, Medicare, Medicaid, self-pay/no insurance, drug abuse, renal failure, chronic pulmonary disorder, diabetes, depression, and fluid and electrolyte disorder were associated with higher readmission risk after hospitalization for CHF. The RAHF scale was created and explained the 95% of readmission variability within the validation cohort. The RAHF scale was then used to define the following three levels of risk for readmission: low (RAHF score <12; 7.58% readmission rate), moderate (RAHF score 12–15; 9.78% readmission rate), and high (RAHF score >15; 12.04% readmission rate). The relative risk of readmission was 1.67 for the high-risk group compared with the low-risk group. Conclusion: The RAHF scale reliably predicts a patient’s 30-day CHF readmission risk based on demographic and clinical factors present upon initial admission. By risk-stratifying patients, using models such as the RAHF scale, strategies tailored to each patient can be implemented to improve patient outcomes and reduce health care costs. Keywords: heart failure, readmission, risk factors, risk assessment, RAHF scale, hospital readmission reduction program, HRRP, SID databas

Alzheimer's disease : insights for risk evaluation and prevention in the Chinese population and the need for a comprehensive programme in Hong Kong/China

201901 bcrcVersion of RecordPublishe