Research Spotlight

Iskandar, M., Fingerhut, A. and Ferzli, G. (2021). “Posterior infundibular dissection: safety first in laparoscopic cholecystectomy.” Surg Endosc Feb 8. [Epub ahead of print].

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BACKGROUND: Laparoscopic cholecystectomy is still fraught with bile duct injuries (BDI). A number of methods such as intra-operative cholangiography, use of indocyanine green (ICG) with infrared imaging, and the critical view of safety (CVS) have been suggested to ensure safer Laparoscopic cholecystectomy (LC).To these, we add posterior infundibular dissection as the initial operative maneuver during LC. Here, we report specific technical details of this approach developed over 30 years with no bile duct injuries and update our experience in 1402 LC. METHODS: In this manuscript, we present a detailed and illustrated description of a posterior infundibular dissection as the initial approach to laparoscopic cholecystectomy (LC). This technique developed after thirty years of experience with LC and have used it routinely over the past ten years with no bile duct injury. RESULTS: Between January of 2010 and December 2019, 1402 Laparoscopic cholecystectomies were performed using the posterior infundibular approach. Operations performed on elective basis constituted 80.3% (1122/1402) and 19.97% were emergent (280/1402). One intra-operative cholangiogram was performed after a posterior sectoral duct was identified. There was one conversion to open cholecystectomy due to bleeding. There were 4 bile leaks that were managed with endoscopic retrograde cholangio-pancreatography (ERCP). There were no bile duct injuries. CONCLUSION: Adopting an initial posterior mobilization of the gallbladder infundibulum lessens the need for medial and cephalad dissection to the node of Lund, allowing for a safer laparoscopic cholecystectomy. In fact the safety of the technique comes from the initial dissection of the lateral border of the infundibulum. The risk of BDI can be reduced to null as was our experience. This approach does not preclude the use of other intra-operative maneuvers or methods.

Powles, T., Atkins, M.B., Escudier, B., Motzer, R.J., Rini, B.I., Fong, L., Joseph, R.W., Pal, S.K., Sznol, M., Hainsworth, J., Stadler, W.M., Hutson, T.E., Ravaud, A., Bracarda, S., Suarez, C., Choueiri, T.K., Reeves, J., Cohn, A., Ding, B., Leng, N., Hashimoto, K., Huseni, M., Schiff, C. and McDermott, D.F. (2021). “Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial.” Eur Urol Mar 4;S0302-2838(21)00003-8. [Epub ahead of print].

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BACKGROUND: The use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively. OBJECTIVE: To evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC. DESIGN, SETTING, AND PARTICIPANTS: IMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab. INTERVENTION: Patients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods. RESULTS AND LIMITATIONS: Fifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19-37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6-13.7) mo. The median event follow-up duration was 19.4 (12.9-21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors. CONCLUSIONS: The atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC. PATIENT SUMMARY: Patients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable.

Liang, F., Xu, Q., Jiang, M., Feng, R., Jiang, S., Yuan, B., Xu, S., Wu, T., Wang, F. and Huang, J.H. (2021). “Emotion Induced Monoamine Neuromodulator Release Affects Functional Neurological Disorders.” Front Cell Dev Biol 9: 633048.

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Functional neurologic disorders (FNDs), also called conversion disorder (previously called hysteria), can show almost all the symptoms of other neurological diseases, including both physical (for example, seizure, weakness, fatigue) and psychological (for instance, depression, anxiety) symptoms. In spite of our general knowledge about emotional processes and developmental defects in the formation of these somatic symptoms, there is still no systemic and comprehensive research on the effects of emotional developmental variables in FND. Recently, both experimental and theoretical emotion studies have been greatly increased, such as prediction error, conceptual act model, basic emotional theory, and monoamine neuromodulator based three primary emotions. In addition, a large amount of evidence has confirmed the role of psychosocial adversity (such as stressful life events, interpersonal difficulties) as an important risk factor for FND. Here, we review recent advances about emotional stress on FND, and pay special attention to the effects of monoamine neuromodulators, such as how norepinephrine and serotonin affect behaviors. Then, we discuss the significance of these changes for FND, which may contribute to clarifying the pathogenesis of FND, and thus provide potential therapeutic drug targets or psychological intervention methods in the future.

Howell, A., Havens, L., Swinford, W. and Arroliga, A. (2021). “PPE Effectiveness – Yes, the Buck and Virus can Stop Here.” Infect Control Hosp Epidemiol Feb 19;1-3. [Epub ahead of print].

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We conducted an observational study of a multi-center healthcare system to determine the effectiveness of our infection control/PPE program during the care of COVID-19 patients. The COVID-19 conversion rate in the patient care setting was 0.70%. Comparatively, the conversion rate noted in the non-patient care/community setting was 15.17%.

Gottlieb, R.L., Nirula, A., Chen, P., Boscia, J., Heller, B., Morris, J., Huhn, G., Cardona, J., Mocherla, B., Stosor, V., Shawa, I., Kumar, P., Adams, A.C., Van Naarden, J., Custer, K.L., Durante, M., Oakley, G., Schade, A.E., Holzer, T.R., Ebert, P.J., Higgs, R.E., Kallewaard, N.L., Sabo, J., Patel, D.R., Klekotka, P., Shen, L. and Skovronsky, D.M. (2021). “Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial.” Jama 325(7): 632-644.

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IMPORTANCE: Coronavirus disease 2019 (COVID-19) continues to spread rapidly worldwide. Neutralizing antibodies are a potential treatment for COVID-19. OBJECTIVE: To determine the effect of bamlanivimab monotherapy and combination therapy with bamlanivimab and etesevimab on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in mild to moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: The BLAZE-1 study is a randomized phase 2/3 trial at 49 US centers including ambulatory patients (N = 613) who tested positive for SARS-CoV-2 infection and had 1 or more mild to moderate symptoms. Patients who received bamlanivimab monotherapy or placebo were enrolled first (June 17-August 21, 2020) followed by patients who received bamlanivimab and etesevimab or placebo (August 22-September 3). These are the final analyses and represent findings through October 6, 2020. INTERVENTIONS: Patients were randomized to receive a single infusion of bamlanivimab (700 mg [n = 101], 2800 mg [n = 107], or 7000 mg [n = 101]), the combination treatment (2800 mg of bamlanivimab and 2800 mg of etesevimab [n = 112]), or placebo (n = 156). MAIN OUTCOMES AND MEASURES: The primary end point was change in SARS-CoV-2 log viral load at day 11 (±4 days). Nine prespecified secondary outcome measures were evaluated with comparisons between each treatment group and placebo, and included 3 other measures of viral load, 5 on symptoms, and 1 measure of clinical outcome (the proportion of patients with a COVID-19-related hospitalization, an emergency department [ED] visit, or death at day 29). RESULTS: Among the 577 patients who were randomized and received an infusion (mean age, 44.7 [SD, 15.7] years; 315 [54.6%] women), 533 (92.4%) completed the efficacy evaluation period (day 29). The change in log viral load from baseline at day 11 was -3.72 for 700 mg, -4.08 for 2800 mg, -3.49 for 7000 mg, -4.37 for combination treatment, and -3.80 for placebo. Compared with placebo, the differences in the change in log viral load at day 11 were 0.09 (95% CI, -0.35 to 0.52; P = .69) for 700 mg, -0.27 (95% CI, -0.71 to 0.16; P = .21) for 2800 mg, 0.31 (95% CI, -0.13 to 0.76; P = .16) for 7000 mg, and -0.57 (95% CI, -1.00 to -0.14; P = .01) for combination treatment. Among the secondary outcome measures, differences between each treatment group vs the placebo group were statistically significant for 10 of 84 end points. The proportion of patients with COVID-19-related hospitalizations or ED visits was 5.8% (9 events) for placebo, 1.0% (1 event) for 700 mg, 1.9% (2 events) for 2800 mg, 2.0% (2 events) for 7000 mg, and 0.9% (1 event) for combination treatment. Immediate hypersensitivity reactions were reported in 9 patients (6 bamlanivimab, 2 combination treatment, and 1 placebo). No deaths occurred during the study treatment. CONCLUSIONS AND RELEVANCE: Among nonhospitalized patients with mild to moderate COVID-19 illness, treatment with bamlanivimab and etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11; no significant difference in viral load reduction was observed for bamlanivimab monotherapy. Further ongoing clinical trials will focus on assessing the clinical benefit of antispike neutralizing antibodies in patients with COVID-19 as a primary end point. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04427501.