2 Minute Medicine Rewind August 10, 2020

Robotic Approach to Paraesophageal Hernia Repair Results in Low Long-Term Recurrence Rate and Beneficial Patient-Centered Outcomes

1. The use of robotic techniques to repair paraesophageal hernias resulted in low rates of recurrence and had positive patient outcomes at five years.

Evidence Rating Level: 3 (Average)

Since the advent of laparoscopic surgery in the 1980s, morbidity and mortality involving the repair of paraesophageal hernias (PEHs) has dramatically reduced. It is estimated, however, that the rate of recurrence of PEH is as high as 57% at some high-volume centers. Furthermore, PEH repair is one of the more demanding and technically challenging procedures in the foregut; thus, there is room for improvement in outcomes, in this instance with the use of robotic surgery. This prospective cohort study involved 233 patients (mean [SD] age = 67.8 [11.3] years, 66.1% female) who underwent either primary repair or secondary revision of a symptomatic PEH using a robotic surgery approach. Primary outcomes assessed serially over five years included the gastroesophageal reflux disease-health related quality of life questionnaire (GERD-HRQL) score, a standardized symptom questionnaire, and screening for recurrence with an esophagram. Five-year post-operative data were available for 145 (62%) patients. 70% of patients underwent primary repair while 30% underwent secondary revision. It was found that 13 of 145 patients experienced recurrence, with the most common residual symptoms being heartburn (12 of 145), bloating (11 of 145), and regurgitation (8 of 145). Average GERD-HRQL score was found to be significantly reduced when comparing pre-operative to five-year post-operative scores (25.6±8.7 vs. 4.5±1.7, 95% CI 19.7 to 22.5). Furthermore, between the pre-operative and the five-year post-operative cohorts, there were substantial reductions in occasional-to-daily anti-reflux medication usage (63.1% vs 13.8%, OR 0.094, 95% CI 0.054 to 0.161) and symptoms of dysphagia (11.2% vs. 2.8%, OR 0.224, 95% CI 0.076 to 0.652). Overall, this study suggested that robotic repair of PEHs is a safe, well-tolerated procedure with low rates of recurrence, results in a positive lifestyle impact among patients, and may represent a viable alternative to laparoscopic repair.

 

Afabicin, a first-in-class anti-staphylococcal antibiotic, in the treatment of acute bacterial skin and skin structure infections: clinical non-inferiority to vancomycin/linezolid

1. Afabicin, a novel, narrow-spectrum antibiotic, was found to be non-inferior to vancomycin and linezolid in treating staphylococcal skin and soft tissue infections.

Evidence Level Rating: 1 (Excellent)

Staphylococcus spp., especially Staphylococcus aureus, are the predominant agents responsible for many serious infections, including acute bacterial skin and skin structure infections (ABSSSIs), infective endocarditis, and prosthetic device infections. Numerous antibiotics are used to treat staphylococcal infections, yet many exhibit reduced efficacy due to antibiotic resistance. In particular, there are many concerns regarding the safety, resistance, and oral bioavailability of agents used to treat ABSSSIs. As such, the need for new agents to treat staphylococcal ABSSSIs are essential. Afabicin is novel antibiotic designed specifically to target fatty acid synthesis in Staphylococcus spp. The objective of this double-blinded, randomized, phase 2 study was to evaluate the efficacy, safety, and tolerability of IV and oral afabicin compared with IV vancomycin and oral linezolid in the treatment of staphylococcal ABSSSIs. Patients were randomized 1:1:1, with 92 patients (mean [SD] age = 43.8 [11.9] years, 66.3% male) receiving low-dose afabicin (80 mg IV BID followed by 120 mg PO BID); 91 patients (mean [SD] age = 42.3 [11.7] years, 65.9% male) receiving high-dose afabicin (160 mg IV BID followed by 240 mg PO BID); and 101 patients (mean [SD] age = 44.9 [10.6] years, 72.6% male) receiving vancomycin/linezolid (vancomycin 1 g IV or 15 mg/kg BID followed by linezolid 600 mg PO BID). All patients received at least two doses of IV antibiotics, after which the decision to transition to oral antibiotics was made at the discretion of the clinician. The primary outcome was clinical response, defined as size change in primary ABSSSI lesion, at 48 to 72 hours. Both low- and high-dose afabicin were found to be non-inferior to vancomycin/linezolid (low-dose: difference -3.5%, 95% CI -10.8 to 3.9%; high-dose: difference 1.0%, 95% CI -7.3 to 9.2%). Furthermore, all patients in the high- and low-dose afabicin groups who had polymicrobial infections were responders for the primary outcome. The most common adverse effect attributed to the intervention was headache, 17.8% in the high-dose afabicin group, compared with 9.1% in the low-dose and 10.3% in the vancomycin/linezolid groups. Overall, this phase 2 trial demonstrated that two different doses and routes of administration of afabicin were non-inferior to, well-tolerated, and showed minimal side effects in the treatment of ABSSSIs when compared with treatment with vancomycin or linezolid. This represents an exciting new development in the realm of narrow-spectrum antibiotics that aligns not only with positive patient outcomes but also with antibiotic stewardship.

 

Intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): a randomized, placebo-controlled, double-blinded trial

1. Among post-myocardial infarction patients with left ventricular dysfunction, an infusion of cardiosphere-derived cells did not significantly reduce scar size at six months.

2. Favorable changes among the infusion cohort, however, were noted in markers of left ventricular remodeling and heart failure.

Evidence Level Rating: 1 (Excellent)

Cardiovascular disease is responsible for significant morbidity and mortality worldwide. Novel treatments are always in the pipeline, including the use of cardiosphere-derived cells (CDCs), heart progenitor cells that have been studied for use in regenerative therapy post-myocardial infarction (MI), hypoplastic left heart syndrome, and dilated cardiomyopathy. This study was a double-blinded, randomized, placebo-controlled trial evaluating the safety and efficacy of intracoronary administration of allogeneic CDCs in patients with post-MI left ventricular (LV) dysfunction. The primary endpoint was the percent change in scar (infarct) size in an antibody-matched cohort at 12 months post-infusion as assessed by contrast-enhanced MRI. 90 patients (mean [SD] age = 55 [11] years, 84.4% male) were randomized to receive an infusion of CDCs, while 44 patients (mean [SD] age = 54 [10] years, 86.4% male) received a placebo. 121 patients were antibody-matched while 13 were antibody-mismatched. It was found that there was no statistically significant change in scar size between the CDC and placebo groups (-5.0±7.4% vs. -4.1±9.1%, p = 0.54). However, the infusion of CDCs had a favorable impact on six-month percent change in LV end-diastolic volume (p = 0.02) and LV end-systolic volume (p = 0.02), as well as NT-proBNP levels (p = 0.02). Adverse events were infrequent in both groups. Of note, no patient mounted an immune response to infused CDCs. The study was terminated early at six months due to concern for futility; thus, the primary endpoint was assessed at six rather than 12 months. Overall, this trial showed that an infusion of CDCs in patients with post-MI LV dysfunction did not significantly reduce scar size when compared with placebo, the primary endpoint. It did, however, favorably impact secondary endpoints, such as LV end-systolic/diastolic volumes, markers of LV remodeling, and NT-proBNP levels, a marker of heart failure. As the infusion was shown to be safe and well-tolerated, more research is needed to determine if alternate dosing regimens or routes of administration have any benefit for select patients.

 

Low serum albumin concentration predicts the need for surgical intervention in neonates with necrotising enterocolitis

1. Among infants with necrotizing enterocolitis, serum albumin ≤ 20 g/L was associated with a significantly greater likelihood of requiring surgical intervention.

Evidence Level Rating: 2 (Good)

Necrotizing enterocolitis (NEC) is the most common emergent condition affecting the gastrointestinal tract of neonates, and predominantly prevalent in premature and low birth weight infants during the first week of life. Mortality is high, between 12 and 32%, especially among infants requiring surgical intervention. The purpose of this retrospective cohort study was to evaluate the predictive role of serum albumin (SA) in identifying neonates with NEC that eventually went on to require surgery. 151 infants (median [range] age = 28.2 [23.1-39.0] weeks, 57% male) with confirmed NEC were identified. 132 infants had NEC Bell’s stage 2, while 19 had NEC Bell’s stage 3. Among NEC Bell’s stage 2 infants, 64.7% ultimately required surgical intervention. SA ≤ 20 g/L (or 2 g/dL) at day one of diagnosis was associated with a higher risk of needing surgery (OR 4.32, 95% CI 1.50 to 12.46, p = 0.007), with an increasing likelihood seen at day two (OR 3.44, 95% CI 1.53 to 7.71, p = 0.003). Other risk factors – including male sex, gestational age ≤ 28 weeks, and birth weight ≤ 1000 g – were also associated with the need for surgery, but only SA ≤ 20 g/L on day two of diagnosis remained significant after multivariate analysis, with an aOR of 3.14 (p = 0.019). ROC curve analysis revealed that SA ≤ 20 g/L at day two of diagnosis had a sensitivity of 41.0% and a specificity of 83.3% in predicting the need for future surgical intervention in neonates with NEC Bell’s stage 2. The positive and negative predictive values were 71.4% and 58.1%, respectively. In all, this study suggested that SA level is a useful biomarker for the severity of NEC among infants that predicts the need for future surgical intervention and may be a tool clinicians can use to risk stratify patients.

 

Maternal Use of Specific Antidepressant Medications During Early Pregnancy and the Risk of Selected Birth Defects

1. Many first-line agents for depression and anxiety – including specific SSRIs, bupropion, and especially venlafaxine – were associated with an increased risk of birth defects if used during early pregnancy.

Evidence Level Rating: 2 (Good)

The management of depression and anxiety during pregnancy is challenging, especially considering that they affect 7.1% and 19.1%, respectively, of the US adult population. As such, a robust understanding of the teratogenicity of drugs used to treat depression and anxiety is of the essence. This case-control study used data from the National Birth Defects Prevention Study (NBDPS) to examine associations between the use of specific antidepressants and select birth defects. 30,630 case mothers of infants with birth defects and 11,478 control mothers were included for analysis. Among them, 1,562 case mothers and 467 control mothers reported antidepressant use during early pregnancy. Mothers with antidepressant exposure during early pregnancy were compared with (1) mothers unexposed before or during pregnancy, and (2) mothers exposed only outside of pregnancy. In set one, mothers using venlafaxine during early pregnancy had an elevated risk for most examined birth defects, with some associations being quite strong (aORs 3.34 [95% CI 1.69 to 6.60] – 5.26 [95% CI 1.96 to 14.12]). Furthermore, it was found that among mothers using SSRIs, paroxetine and fluoxetine resulted in the highest risk for specific birth defects. No association between escitalopram use and birth defects was seen. In set two, many of the previously observed findings were attenuated, with some notable exceptions. Fluoxetine use was associated with coarctation of the aorta (aOR 2.06, 95% CI 0.89 to 4.74), while citalopram use was associated with atrioventricular septal defect (aOR 3.73, 95% CI 0.86 to 16.27). Despite adjusting for underlying conditions, the associations observed with venlafaxine use largely persisted; in some instances, such as for anencephaly and craniorachischisis, the association strengthened (aOR 9.14, 95% CI 1.91 to 43.83). Additionally, bupropion was associated with an increased risk of diaphragmatic hernia (aOR 6.50, 95% CI 1.85 to 22.88). In all, this study suggested that the use of specific SSRIs, bupropion, and venlafaxine during early pregnancy carry a varying risk of causing birth defects. Venlafaxine use, in particular, was associated with multiple birth defects. These data represent the first effort to characterize the teratogenic effects of specific antidepressants, and more work is needed to validate these findings.

Image: PD

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