Surgical treatment of GERD: systematic review and meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) has a high worldwide prevalence in adults and children. There is uncertainty regarding medical versus surgical therapy and different surgical techniques. This review assessed outcomes of antireflux surgery versus medical management of GERD in adults and children, robotic versus laparoscopic fundoplication, complete versus partial fundoplication, and minimal versus maximal dissection in pediatric patients. METHODS: PubMed, Embase, and Cochrane databases were searched (2004-2019) to identify randomized control and non-randomized comparative studies. Two independent reviewers screened for eligibility. Random effects meta-analysis was performed on comparative data. Study quality was assessed using the Cochrane Risk of Bias and Newcastle Ottawa Scale. RESULTS: From 1473 records, 105 studies were included. Most had high or uncertain risk of bias. Analysis demonstrated that anti-reflux surgery was associated with superior short-term quality of life compared to PPI (Std mean difference = - 0.51, 95%CI - 0.63, - 0.40, I2 = 0%) however short-term symptom control was not significantly superior (RR = 0.75, 95%CI 0.47, 1.21, I2 = 82%). A proportion of patients undergoing operative treatment continue PPI treatment (28%). Robotic and laparoscopic fundoplication outcomes were similar. Compared to total fundoplication, partial fundoplication was associated with higher rates of prolonged PPI usage (RR = 2.06, 95%CI 1.08, 3.94, I2 = 45%). There was no statistically significant difference for long-term symptom control (RR = 0.94, 95%CI 0.85, 1.04, I2 = 53%) or long-term dysphagia (RR = 0.73, 95%CI 0.52, 1.02, I2 = 0%). Ien, minimal dissection during fundoplication was associated with lower reoperation rates than maximal dissection (RR = 0.21, 95%CI 0.06, 0.67). CONCLUSIONS: The available evidence regarding the optimal treatment of GERD often suffers from high risk of bias. Additional high-quality randomized control trials may further inform surgical decision making in the treatment of GERD.

Tailored approach to gastroparesis significantly improves symptoms.

BACKGROUND: Gastroparesis is difficult to treat and many patients do not report relief of symptoms with medical therapy alone. Several operative approaches have been described. This study shows the results of our selective surgical approach for patients with gastroparesis. MATERIALS AND METHODS: This is a retrospective study of prospective data from our electronic medical record and data symptom sheet. All patients had a pre-operative gastric emptying study showing gastroparesis, an esophagogastroduodenoscopy, and either a CT or an upper GI series with small bowel follow-through. All patients had pre- and post-operative symptom sheets where seven symptoms were scored for severity and frequency on a scale of 0-4. The scores were analyzed by a professional statistician using paired sample t test. RESULTS: 58 patients met inclusion criteria. 33 had gastric stimulator (GES), 7 pyloroplasty (PP), 16 with both gastric stimulator and pyloroplasty (GSP), and 2 sleeve gastrectomy. For patients in the GSP group, the second procedure was performed if there was inadequate improvement with the first procedure. There was no mortality. The follow-up period was 6-316 weeks (mean 66.107, SD 69.42). GES significantly improved frequency and severity for all symptoms except frequency of bloating and postprandial fullness. PP significantly improved nausea and vomiting severity, frequency of nausea, and early satiety. Symptom improvement for GSP was measured from after the first to after the second procedure. GSP significantly improved all but vomiting severity and frequency of early satiety, postprandial fullness, and epigastric pain. CONCLUSION: All procedures significantly improved symptoms, although numbers are small in the PP group. GES demonstrates more improvement than PP, and if PP or GES does not adequately improve symptoms GSP is appropriate. In our practice, gastrectomy was reserved as a last resort.

Antibiotics for ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a significant cause of morbidity and mortality, complicating the medical course of approximately 10% of mechanically-ventilated patients, with an estimated attributable mortality of 13%. To treat VAP empirically, the American Thoracic Society currently recommends antibiotic therapy based on the patients' risk of colonisation by an organism with multidrug resistance. The selection of initial antibiotic therapy in VAP is important, as inappropriate initial antimicrobial treatment is associated with higher mortality and longer hospital stay in intensive care unit (ICU) patients.While guidelines exist for the antibiotic treatment of hospital-acquired pneumonia (HAP) from the American Thoracic Society and the British Society for Antimicrobial Chemotherapy, there are many limitations in the quality of available evidence. This systematic review aimed to summarise the results of all randomised controlled trials (RCTs) that compare empirical antibiotic regimens for VAP. OBJECTIVES: The primary objective of this review was to assess the effect of different empirical antimicrobial therapies on the survival and clinical cure of adult patients with ventilator-associated pneumonia (VAP). Secondary objectives included reporting the incidence of adverse events, new superinfections, length of hospital stay, and length of intensive care unit (ICU) stay associated with these therapies. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CINAHL and Web of Science to December 2015; we searched ClinicalTrials.gov to September 2016. SELECTION CRITERIA: Two review authors independently assessed RCTs comparing empirical antibiotic treatments of VAP in adult patients, where VAP was defined as new-onset pneumonia that developed more than 48 hours after endotracheal intubation. Physicians and researchers were not required to be blinded for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted study data. We pooled studies and analysed them in two ways. We examined monotherapy, or a single experimental antimicrobial drug, versus combination therapy, or multiple experimental antimicrobial drugs. We also examined carbapenem therapy versus non-carbapenem therapy. MAIN RESULTS: We included 12 studies with 3571 participants. All included studies examined the empiric use of one antimicrobial regimen versus another for the treatment of adults with VAP, but the particular drug regimens examined by each study varied. There was potential for bias because some studies did not report outcomes for all participants. All but one study reported sources of funding or author affiliations with pharmaceutical companies.We found no statistical difference in all-cause mortality between monotherapy and combination therapy (N = 4; odds ratio (OR) monotherapy versus combination 0.97, 95% confidence interval (CI) 0.73 to 1.30), clinical cure (N = 2; OR monotherapy versus combination 0.88, 95% CI 0.56 to 1.36), length of stay in ICU (mean difference (MD) 0.65, 95% CI 0.07 to 1.23) or adverse events (N = 2; OR monotherapy versus combination 0.93, 95% CI 0.68 to 1.26). We downgraded the quality of evidence for all-cause mortality, adverse events, and length of ICU stay to moderate for this comparison. We determined clinical cure for this comparison to be of very low-quality evidence.For our second comparison of combination therapy with optional adjunctives only one meta-analysis could be performed due to a lack of trials comparing the same antibiotic regimens. Two studies compared tigecycline versus imipenem-cilastatin for clinical cure in the clinically evaluable population and there was a statistically significant increase in clinical cure for imipenem-cilastatin (N = 2; OR tigecycline versus imipenem-cilastatin 0.44, 95% CI 0.23 to 0.84). Of importance, this effect was due to a single study.We found no statistical difference in all-cause mortality between carbapenem and non-carbapenem therapies (N = 1; OR carbapenem versus non-carbapenem 0.59, 95% CI 0.30 to 1.19) or adverse events (N = 3; OR carbapenem versus non-carbapenem 0.78, 95% CI 0.56 to 1.09), but we found that carbapenems are associated with a statistically significant increase in the clinical cure (N = 3; OR carbapenem versus non-carbapenem 1.53, 95% CI 1.11 to 2.12 for intention-to-treat (ITT) analysis and N = 2; OR carbapenem versus non-carbapenem 2.29, 95% CI 1.19 to 4.43 for clinically evaluable patients analysis). For this comparison we downgraded the quality of evidence for mortality, and clinical cure (ITT and clinically evaluable populations) to moderate. We determined the quality of evidence for adverse events to be low. AUTHORS' CONCLUSIONS: We did not find a difference between monotherapy and combination therapy for the treatment of people with VAP. Since studies did not identify patients with increased risk for multidrug-resistant bacteria, these data may not be generalisable to all patient groups. However, this is the largest meta-analysis comparing monotherapy to multiple antibiotic therapies for VAP and contributes further evidence to the safety of using effective monotherapy for the empiric treatment of VAP.Due to lack of studies, we could not evaluate the best antibiotic choice for VAP, but carbapenems as a class may result in better clinical cure than other tested antibiotics.

Factors That Predict Biological Aggressiveness in Estrogen Receptor-Positive / Human Epidermal Growth Factor Receptor 2-Negative / Lymph Node-Negative Breast Cancer.

Background: Traditionally, breast cancer is staged using TNM criteria: tumor size (T), nodal status (N), and metastasis (M). The Oncotype DX assay provides a recurrence score (RS) based on genomics that predicts the likelihood of distant recurrence in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-)/lymph node-negative (LN-) tumors. Methods: We retrospectively reviewed the medical records of patients with ER+/HER2-/LN- breast cancer tumors who were evaluated between 2007 and 2017 with Oncotype DX RS. We compared the RS to tumor size, patient age, progesterone receptor (PR) status, and LN immunohistochemistry to assess for factors that may independently predict recurrence risk. We also compared tumor size to tumor grade. Results: The data set included 296 tumors: 248 ER+/PR-positive (PR+)/HER2- and 48 ER+/PR-negative (PR-)/HER2-. RS ranged from 0 to 66, patient age ranged from 33 to 77 years, and tumor size ranged from 1 to 65 mm. No significant correlation was found between age and RS (r=-0.073, P=0.208). PR- tumors had a significantly higher RS regardless of size (PR- mean RS 30.8 ± 12.7; PR+ mean RS 16.3 ± 7.3; t(53)=7.6, P<0.0001). No significant correlation was seen between tumor size and RS for all tumors (r=-0.028, P=0.635), and this finding remained true for the PR+ tumor subgroup (r=0.114, P=0.072). However, a significant negative correlation was seen between tumor size and RS in the PR- subgroup (r=-0.343, P=0.017). Further analysis to ensure that differences in tumor grade did not account for this correlation showed equal distribution of well differentiated, moderately differentiated, and poorly differentiated tumors with no significant correlation between tumor size and grade. Conclusion: Increasing tumor size may not be associated with increasing biological aggressiveness. Traditionally, smaller tumors are thought to be lower risk and larger tumors higher risk, with a tendency to use chemotherapy with large tumors. However, our data showed a negative correlation between tumor size and RS in the PR- subgroup. A tumor with PR negativity that reaches a large size without metastasizing may suggest a favorable tumor biology. These tumors may not receive as much benefit from chemotherapy as previously thought. Also, the higher RS seen in smaller PR- tumors may demonstrate PR- status as a predictor for higher risk of distant recurrence. We propose that all tumors meeting the ER+/PR-/LN- criteria, regardless of size, should be considered for genotyping, with the RS used to guide chemotherapy benefit.