Estimating the effect of nintedanib on forced vital capacity in children and adolescents with fibrosing interstitial lung disease using a Bayesian dynamic borrowing approach.

BACKGROUND: The rarity of childhood interstitial lung disease (chILD) makes it challenging to conduct powered trials. In the InPedILD trial, among 39 children and adolescents with fibrosing ILD, there was a numerical benefit of nintedanib versus placebo on change in forced vital capacity (FVC) over 24 weeks (difference in mean change in FVC % predicted of 1.21 [95% confidence interval: -3.40, 5.81]). Nintedanib has shown a consistent effect on FVC across populations of adults with different diagnoses of fibrosing ILD. METHODS: In a Bayesian dynamic borrowing analysis, prespecified before data unblinding, we incorporated data on the effect of nintedanib in adults and the data from the InPedILD trial to estimate the effect of nintedanib on FVC in children and adolescents with fibrosing ILD. The data from adults were represented as a meta-analytic predictive (MAP) prior distribution with mean 1.69 (95% credible interval: 0.49, 3.08). The adult data were weighted according to expert judgment on their relevance to the efficacy of nintedanib in chILD, obtained in a formal elicitation exercise. RESULTS: Combined data from the MAP prior and InPedILD trial analyzed within the Bayesian framework resulted in a median difference between nintedanib and placebo in change in FVC % predicted at Week 24 of 1.63 (95% credible interval: -0.69, 3.40). The posterior probability for superiority of nintedanib versus placebo was 95.5%, reaching the predefined success criterion of at least 90%. CONCLUSION: These findings, together with the safety data from the InPedILD trial, support the use of nintedanib in children and adolescents with fibrosing ILDs.

Functional gallbladder disorder: Interim analysis of a prospective cohort study.

BACKGROUND: Functional gallbladder disorder (FGBD) remains a controversial indication for cholecystectomy. METHODS: A prospective cohort study enrolled patients strictly meeting Rome criteria for FGBD, and cholecystectomy was performed. They were assessed pre- and 3 and 6 months postoperatively with surveys of abdominal pain and quality of life (RAPID and SF-12 surveys, respectively). Interim analysis was performed. RESULTS: Although neither ejection fraction nor pain reproduction predicted success after cholecystectomy, the vast majority of enrolled patients had a successful outcome after undergoing cholecystectomy for FGBD: of a planned 100 patients, 46 were enrolled. Of 31 evaluable patients, 26 (83.9 â€‹%) reported RAPID improvement and 28 (93.3 â€‹%) SF12 improvement at 3- or 6-month follow-up. CONCLUSION: FGBD, strictly diagnosed, should perhaps no longer be a controversial indication for cholecystectomy, since its success rate for biliary pain in this study was similar to that for symptomatic cholelithiasis. Larger-scale studies or randomized trials may confirm these findings.

Predictors of In-Hospital Mortality Following Pancreatectomy.

BACKGROUND: In-hospital mortality rates following all types of pancreatic resections (PRs) have decreased over recent decades. Our aim was to identify predictors of in-hospital mortality following pancreatic resection. METHODS: All patients undergoing pancreatic resection were sampled from the National Inpatient Sample (NIS) in the years 2007-2012. Predictors of in-hospital mortality were identified and incorporated into a binary logistic regression model. RESULTS: A total of 111,568 patients underwent pancreatectomy. Annual mortality rates decreased from 4.3% in 2007 to 3.5% in 2012. Independent predictors of in-hospital mortality included age ≥75 years (vs. <65 years, OR = 2.04; 95% CI: 1.61-2.58), nonelective procedure status (OR = 1.46; 95% CI: 1.19-1.80), resection other than distal pancreatic resection (vs. Whipple, OR = 2.14; 95% CI: 1.71-2.69; other partial, OR = 2.48; 95% CI: 1.76-3.48), lower hospital volume (OR = 1.28; 95% CI: 1.09-1.49), indication for pancreatic resection other than benign diseases (vs. malignant, OR = 1.63; 95% CI: 1.25-2.15; other, OR = 2.48; 95% CI: 1.76-3.48), pulmonary complications (OR = 12.36; 95% CI: 10.11-15.17), infectious complications (OR = 2.17; 95% CI: 1.78-2.64), noninfectious wound complications and pancreatic leak (OR = 1.94; 95% CI: 1.53-2.46), and acute myocardial infarction (OR = 2.03; 95% CI: 1.32-3.06). DISCUSSION: Our findings identify predictors of inpatient mortality following pancreatectomy, with pulmonary complications representing the single most significant factor for increased mortality. These findings complement and expand on previously published data and, if applied to perioperative care, may enhance survival following pancreatectomy.

Seasonality in General Surgery Hospitalizations and Procedures in the US: Workflow Implications.

INTRODUCTION: Seasonality has been studied in select conditions treated by surgeons and internists, but is not well understood regarding overall procedural volume in general surgery. Furthermore, much of the literature is limited due to lack of use of seasonal-trend-decomposition analyses. METHODS: All admissions with general surgery procedures were pooled from NIS 2002-2014, monthly hospitalization rates calculated, and seasonal-trend decomposition performed. RESULTS: Emergent admissions, accounting for 9% of the average annual incidence, had more prominent seasonality than elective admissions. Inpatient surgical-procedural volume remained relatively stable throughout the year and decreased only in the third quarter. Procedures for acute intra-abdominal conditions and traumas peaked in summer months, while endoscopies, tracheostomies and gastrostomies peaked in winter months. CONCLUSIONS: Many surgical pathologies and corresponding general-surgery procedures obey circannual patterns. Surgical workforce remains in high demand throughout the year except for fall and winter holidays. Understanding seasonal variation in such demand may be important for staffing and resource planning.

Nintedanib in children and adolescents with fibrosing interstitial lung diseases.

BACKGROUND: Childhood interstitial lung disease (ILD) comprises a spectrum of rare ILDs affecting infants, children and adolescents. Nintedanib is a licensed treatment for pulmonary fibrosis in adults. The primary objectives of the InPedILD trial were to determine the dose-exposure and safety of nintedanib in children and adolescents with fibrosing ILD. METHODS: Patients aged 6-17 years with fibrosing ILD on high-resolution computed tomography and clinically significant disease were randomised 2:1 to receive nintedanib or placebo for 24 weeks and then open-label nintedanib. Dosing was based on weight-dependent allometric scaling. Co-primary end-points were the area under the plasma concentration-time curve at steady state (AUCτ,ss) at weeks 2 and 26 and the proportion of patients with treatment-emergent adverse events at week 24. RESULTS: 26 patients received nintedanib and 13 patients received placebo. The geometric mean (geometric coefficient of variation) AUCτ,ss for nintedanib was 175 µg·h·L-1 (85.1%) in patients aged 6-11 years and 160 µg·h·L-1 (82.7%) in patients aged 12-17 years. In the double-blind period, adverse events were reported in 84.6% of patients in each treatment group. Two patients discontinued nintedanib due to adverse events. Diarrhoea was reported in 38.5% and 15.4% of the nintedanib and placebo groups, respectively. Adjusted mean±se changes in percentage predicted forced vital capacity at week 24 were 0.3±1.3% in the nintedanib group and -0.9±1.8% in the placebo group. CONCLUSIONS: In children and adolescents with fibrosing ILD, a weight-based dosing regimen resulted in exposure to nintedanib similar to adults and an acceptable safety profile. These data provide a scientific basis for the use of nintedanib in this patient population.

Measured versus Estimated Blood Loss: Interim Analysis of a Prospective Quality Improvement Study.

Estimated blood loss (EBL) is an increasingly important factor used to predict outcomes, such as morbidity and mortality, length of stay, and readmissions, after major abdominal operations. However, blood loss is difficult to estimate, with frequent under- and overestimations, consequences of which can be potentially dangerous for individual patients and confounding for scoring systems relying on EBL. We hypothesized that EBL is often inaccurate and have prospectively enrolled consecutive patients undergoing major elective intra-abdominal operations. Actual hemoglobin levels were measured and used to calculate the measured blood loss (MBL), which was compared with the EBL, as estimated both by surgeons (sEBL) and anesthesiologists (aEBL). Of 23 eligible cases at interim analysis, pancreaticoduodenectomy (n = 8) was the most common, followed by colectomy (n = 3), hepatectomy (n = 3) and gastrectomy (n = 2), biliary excision and reconstruction (n = 2), combined gastrectomy + colectomy (n = 1), radical nephrectomy (n = 1), open cholecystectomy (n = 1), pancreatic debridement (n = 1), and exploratory laparotomy (n = 1). aEBL overestimated MBL by 192 mL (143%) on average. The aEBL was significantly greater than the MBL (P = 0.004), whereas the sEBL was significantly less than the MBL (P = 0.009). In conclusion, surgeons significantly underestimate and anesthesiologists significantly overestimate EBL. This finding impacts not only immediate patient care but also the interpretation of scoring systems relying on EBL.

Raoultella ornithinolytica and Klebsiella oxytoca pyogenic liver abscess presenting as chronic cough.

Raoultella ornithinolytica is a Gram-negative rod belonging to the Enterobacteriaceae family and closely related to Klebsiella spp. It is commonly present in aquatic environments. Human infections caused by R. ornithinolytica are being increasingly recognized. It has been documented to cause various hospital-acquired infections including but not limited to gastrointestinal, skin, and genitourinary infections. The organism has been particularly associated with invasive procedures and is commonly seen in patients with malignancy, diabetes, chronic kidney disease and immunodeficiency. To our knowledge, we report the first case of pyogenic liver abscess caused by this organism. The patient presented subtly with a chronic, nonresolving cough and was managed successfully by surgical drainage and appropriate antimicrobials.

Spontaneous inflammation and necrosis of the falciform and round ligaments: a case report and review of the literature.

BACKGROUND: Necrosis of the falciform and round ligaments is extremely rare, thus making the diagnosis challenging. It is often misdiagnosed as gallbladder pathology due to the presenting symptoms. Due to the rarity of this pathology, there is limited literature available. CASE PRESENTATION: A 53-year-old white man presented to our hospital with signs and symptoms of gallbladder pain but turned out to have the rare entity of necrosis of the falciform and round ligaments. An extensive review of the world literature was performed using PubMed. Manual cross-referencing of reference lists was performed to obtain all available articles. The personal operative log of the senior author was also searched to reveal one additional case. Statistical analysis was descriptive only, given the small number of reported cases. Thirty-nine articles were found, among which forty-three case were identified, and one additional case was extracted from the operative log of the senior author. Unlike previous reports, we found that isolated inflammation and necrosis of the ligaments occurs at nearly the same frequency in both men and women, not predominantly in women as previously reported in smaller series. The mean age at presentation was 59.5 years old, and cases were typically initially diagnosed as gallbladder pathology, most commonly acute cholecystitis. Computed tomography more frequently than ultrasound revealed the falciform and round-ligament pathology. CONCLUSIONS: Isolated falciform and round-ligament inflammation and necrosis is a rare condition that is difficult to diagnose because it can present mimicking a wide variety of intra-abdominal pathologies, particularly gallbladder pathologies. It is often best treated by laparoscopic resection. Unlike prior reports, our review of the literature, which is the largest that we know of to date, shows that males and females are equally affected. Greater awareness of this entity will aid in future diagnosis.

Plasmacytoma as a cause of small bowel obstruction in a virgin abdomen in a patient with multiple myeloma: a case report.

BACKGROUND: Multiple myeloma is a hematological malignancy that classically results in an abnormal clonal proliferation of plasma cells in the bone marrow. Extramedullary disease in the setting of multiple myeloma, referred to as secondary extramedullary plasmacytoma, is found in 7-17% of cases of multiple myeloma at the time of diagnosis and can involve any organ system. Small bowel obstruction is a rare but important gastrointestinal manifestation of multiple myeloma that should be considered in patients with multiple myeloma who present with concerning abdominal symptoms. CASE PRESENTATION: We present the case of a 52-year-old African-American man with a history of deep venous thrombosis (he is on anticoagulation) and pathologic fracture secondary to multiple myeloma diagnosed 4 months prior to our encounter. He presented with abdominal pain, constipation, nausea, and vomiting. An abdominal X-ray showed distended bowel loops concerning for bowel obstruction and a contrast-enhanced computed tomography scan of his abdomen and pelvis showed a 5.4 cm soft tissue mass involving a loop of distal ileum. He underwent laparoscopic exploration of his abdomen with small bowel resection and primary anastomosis for a small intussusception. He had an uneventful postoperative course and was discharged on postoperative day 6. CONCLUSIONS: Multiple myeloma has myriad presentations. Gastrointestinal involvement, although rare, can manifest as small bowel obstruction for which early recognition and appropriate surgical management are key to improving outcome. Intussusception is the most common mechanism of obstruction from extramedullary plasmacytoma causing small bowel obstruction and this has been seen in five of six case reports, including this case. It is important to recognize and consider the risks of immunosuppression, venous thromboembolism, and malnutrition in the surgical management of gastrointestinal complications of multiple myeloma.

Airway clearance physiotherapy improves ventilatory dynamics during exercise in patients with cystic fibrosis: a pilot study.

BACKGROUND: Airflow limitation and dynamic hyperinflation may limit exercise capacity in patients with cystic fibrosis (CF). The aim was to investigate whether the undertaking of airway clearance physiotherapy (ACT) prior to cardiopulmonary exercise testing (CPET) results in improvements in exercise capacity. METHODS: A prospective randomised, cross-over pilot study was performed in children aged >9 years. Spirometry, plethysmography and CPET were performed on two separate occasions-one test with ACT prior to CPET and the other without. RESULTS: 12 patients with CF were included in the study with a mean (SD) age of 12.83 (1.85) years. No significant difference in peak oxygen uptake (VO2) was found between the tests. However, lower minute ventilation (VE) and ventilatory equivalents (VEVO2 and VEVCO2) at ventilatory threshold (VT) were noted when ACT was undertaken prior to CPET. The mean(SD) VE (L/min) at VT was 26.67 (5.49) vs 28.92 (6.3) (p=0.05), VEVO2 (L/min) at VT was 24.5 (1.75) vs 26.05 (2.5) (p=0.03) and VEVCO2 (L/min) at VT was 26.58 (2.41) vs 27.98 (2.11) (p=0.03). CONCLUSIONS: These pilot data suggest that ACT prior to exercise may lead to improved ventilatory dynamics during exercise in individuals with CF.

Clues to predict incidental gallbladder cancer.

BACKGROUND: Consequences of incidental gallbladder cancer (iGBC) following cholecystectomy may include repeat operation (depending on T stage) and worse survival (if bile spillage occurred), both avoidable if iGBC were suspected preoperatively. METHODS: A retrospective single-institution review was done. Ultrasound images for cases and controls were blindly reviewed by a radiologist. Chi-square and Student's t tests, as well as logistic regression and Kaplan-Meier analyses were used. A P ≤ 0.01 was considered significant. RESULTS: Among 5796 cholecystectomies performed 2000-2013, 26 (0.45%) were iGBC cases. These patients were older (75.61 versus 52.27 years), had more laparoscopic-to-open conversions (23.1% versus 3.9%), underwent more imaging tests, had larger common bile duct diameter (7.13 versus 5.04 mm) and higher alkaline phosphatase. Ultrasound imaging showed that gallbladder wall thickening (GBWT) without pericholecystic fluid (PCCF), but not focal-versus-diffuse GBWT, was associated significantly with iGBC (73.9% versus 47.4%). On multivariable logistic regression analysis, GBWT without PCCF, and age were the strongest predictors of iGBC. The consequences iGBC depended significantly on intraoperative bile spillage, with nearly all such patients developing carcinomatosis and significantly worse survival. CONCLUSIONS: Besides age, GBWT, dilated common bile duct, and elevated alkaline phosphatase, number of preoperative imaging modalities and the presence of GBWT without PCCF are useful predictors of iGBC. Bile spillage causes poor survival in patients with iGBC.

How much pain relief do patients expect after cholecystectomy?

BACKGROUND: Cholecystectomy is a common operation, increasingly performed, in the USA, for "functional gall bladder disorder" (FGBD). Outcomes of these surgeries are uncertain. In planning a study of FGBD, we needed to define the best outcome measures. METHODS: We sought the opinions of patients (52 with FGBD and 100 with stones for comparison) coming to cholecystectomy. They were asked to respond in four ways about the minimum benefit they would count as "success." RESULTS: We found that most patients do not expect cholecystectomy to relieve their pain-related disability completely, regardless of the presence or absence of stones. CONCLUSIONS: Future studies of the success of surgery should use patient-centered outcome assessments, such as PGIC (patient's global impression of change), in addition to objective measures of the impact of treatment on key symptoms, such as pain.

Minimally invasive and open gallbladder cancer resections: 30- vs 90-day mortality.

BACKGROUND: Minimally invasive surgery is increasingly used for gallbladder cancer resection. Postoperative mortality at 30 days is low, but 90-day mortality is underreported. METHODS: Using National Cancer Database (1998-2012), all resection patients were included. Thirty- and 90-day mortality rates were compared. RESULTS: A total of 36 067 patients were identified, 19 139 (53%) of whom underwent resection. Median age was 71 years and 70.7% were female. Ninety-day mortality following surgical resection was 2.3-fold higher than 30-mortality (17.1% vs 7.4%). There was a statistically significant increase in 30- and 90-day mortality with poorly differentiated tumors, presence of lymphovascular invasion, tumor stage, incomplete surgical resection and low-volume centers (P<0.001 for all). Even for the 1885 patients who underwent minimally invasive resection between 2010 and 2012, the 90-day mortality was 2.8-fold higher than the 30-day mortality (12.0% vs 4.3%). CONCLUSIONS: Ninety-day mortality following gallbladder cancer resection is significantly higher than 30-day mortality. Postoperative mortality is associated with tumor grade, lymphovascular invasion, tumor stage, type and completeness of surgical resection as well as type and volume of facility.

Prepancreatic postduodenal portal vein: a case report and review of the literature.

BACKGROUND: Prepancreatic postduodenal portal vein is extremely rare, with only 13 cases reported in the literature. CASE PRESENTATION: A 55-year-old white woman presented to our emergency department with abdominal pain. She underwent a computed tomography of her abdomen, which showed a portal vein coursing anterolaterally to her pancreas and posteriorly to the first portion of her duodenum, constituting a prepancreatic postduodenal portal vein. Imaging revealed choledocholithiasis, requiring endoscopic sphincterotomy, but due to a history of a gastric bypass procedure, she was lost to follow-up after being referred to an advanced endoscopist. This represents the 14th reported case of prepancreatic postduodenal portal vein. CONCLUSIONS: Awareness of this rare anomaly is paramount, and will help surgeons and interventional radiologists to avoid complications related to inadvertent injury to the portal vein, which could be life-threatening.

Age-related differences pre-, intra-, and postcholecystectomy: A retrospective cohort study of 6,868 patients.

BACKGROUND: Cholecystectomy (CCY) is increasingly performed in older individuals. We sought to examine age-related differences in pre-, intra-, and postoperative factors at a community hospital, using a very large, single-institution cholecystectomy database. MATERIALS AND METHODS: A retrospective review of 6868 patients who underwent CCY from 2001 to 2013 was performed. ROC analysis identified the optimal age cutoff when complications reached a significant inflection point (<55 and ≥55 years). Multiple clinical features and outcomes were measured and compared by age. Logistic regression was used to examine how well a set of covariates predicted postoperative complications. RESULTS: Older patients had significantly higher rates of comorbidities and underwent more extensive preoperative imaging. Intraoperatively, older patients had more blood loss, longer operative times, and more open operations. Postoperatively, older patients experienced more complications and had significantly different pathological findings. While holding age and gender constant, regression analyses showed that preoperative creatinine level, blood loss and history of previous operation were the strongest predictors of complications. The risk for developing complications increased by 2% per year of life. CONCLUSION: Older patients have distinct pre-, intra-, and postoperative characteristics. Their care is more imaging- and cost-intensive. CCY in this population is associated with higher risks, likely due to a combination of comorbidities and age-related worsened physiological status. Pathologic findings are significantly different relative to younger patients. While removing the effect of age, preoperative creatinine levels, blood loss, and history of previous operation predict postoperative complications. Quantifying these differences may help to inform management decisions for older patients.

The role of surgery in the treatment of endoscopic complications.

As the number, diversity, and complexity of endoscopic complications has increased, so too has the number, diversity, and complexity of operative interventions required to treat them. The most common complications of endoscopy in general are bleeding and perforation, but each endoscopic modality has specific nuances of these and other complications. Accordingly, this review considers the surgical complications of endoscopy by location within the gastrointestinal tract, as opposed to by complication types, since there are many complication types that are specific for only one or few locations, such as buried-bumper syndrome after percutaneous endoscopic gastrostomy and pancreatitis after endoscopic retrograde cholangiopancreatography, and since the management of a given complication, such as perforation, may be vastly different in one area than in another area, such as perforations of the esophagus versus the retroperitoneal duodenum versus the intraperitoneal duodenum. It is hoped that this review will provide guidance for gastroenterologists considering a particular procedure, either to assess the risks for surgical complications in preparation for patient counseling, or assist in assessing a patient who seems to be having a severe complication, or to learn what operation might be required to treat a given complication and how that operation might be performed. As with many operations, those for the treatment of endoscopic complications are typically performed only when less invasive, nonoperative strategies fail.