Waning Immunity after the BNT162b2 Vaccine in Israel.

BACKGROUND: In December 2020, Israel began a mass vaccination campaign against coronavirus disease 2019 (Covid-19) by administering the BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a resurgent Covid-19 outbreak began in mid-June 2021. Possible reasons for the resurgence were reduced vaccine effectiveness against the delta (B.1.617.2) variant and waning immunity. The extent of waning immunity of the vaccine against the delta variant in Israel is unclear. METHODS: We used data on confirmed infection and severe disease collected from an Israeli national database for the period of July 11 to 31, 2021, for all Israeli residents who had been fully vaccinated before June 2021. We used a Poisson regression model to compare rates of confirmed SARS-CoV-2 infection and severe Covid-19 among persons vaccinated during different time periods, with stratification according to age group and with adjustment for possible confounding factors. RESULTS: Among persons 60 years of age or older, the rate of infection in the July 11-31 period was higher among persons who became fully vaccinated in January 2021 (when they were first eligible) than among those fully vaccinated 2 months later, in March (rate ratio, 1.6; 95% confidence interval [CI], 1.3 to 2.0). Among persons 40 to 59 years of age, the rate ratio for infection among those fully vaccinated in February (when they were first eligible), as compared with 2 months later, in April, was 1.7 (95% CI, 1.4 to 2.1). Among persons 16 to 39 years of age, the rate ratio for infection among those fully vaccinated in March (when they were first eligible), as compared with 2 months later, in May, was 1.6 (95% CI, 1.3 to 2.0). The rate ratio for severe disease among persons fully vaccinated in the month when they were first eligible, as compared with those fully vaccinated in March, was 1.8 (95% CI, 1.1 to 2.9) among persons 60 years of age or older and 2.2 (95% CI, 0.6 to 7.7) among those 40 to 59 years of age; owing to small numbers, the rate ratio could not be calculated among persons 16 to 39 years of age. CONCLUSIONS: These findings indicate that immunity against the delta variant of SARS-CoV-2 waned in all age groups a few months after receipt of the second dose of vaccine.

Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel.

BACKGROUND: Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance. METHODS: We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition. We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons. RESULTS: Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal. The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46). As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20). The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637. CONCLUSIONS: The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.

The robotic NICE procedure outperforms conventional laparoscopic extracorporeal-assisted colorectal resection: results of a matched cohort analysis.

INTRODUCTION: We introduced the robotic NICE procedure for left-sided colorectal resection in 2018 in which the entire procedure is performed without loss of pneumoperitoneum and without an abdominal wall incision by performing natural orifice-assisted transrectal extraction of the specimen and intracorporeal anastomosis. We compare the results of the NICE procedure versus conventional laparoscopic resection, which was our standard approach prior to 2018. METHODS: A matched pair case-control study compared patients following the NICE procedure versus those who underwent laparoscopic left-sided colorectal resection with conventional extracorporeal-assisted technique. Cases were performed at an Academic Medical Center and recorded in a prospective database to analyze perioperative outcomes. RESULTS: From a total cohort of 352 patients, 83 were matched in each group. When comparing the NICE procedure vs. the Extracorporeal-Assisted laparoscopic group, there were no significant differences in age (58.5 vs. 59.3 years old), sex (47 vs. 42 Female), body mass index (27.4 vs. 27.5 kg/m2), ASA, diagnosis, or type of surgery. Operative time (198.8 vs. 197.7 min), blood loss (56.0 vs. 53.3 ml), intraoperative complications (0.0% vs. 0.0%), and conversion rates (0.0% vs. 0.0%) were similar in both groups. The NICE procedure was associated with significantly earlier return of bowel function (40.7 vs. 23.6 h), shorter length of stay (3.1 vs. 2.2 days), and lower total opioid use (94.6 vs. 70.5 morphine milligram equivalents). Overall, there were no differences in postoperative abscess formation, complications, readmission, or reoperation rates. CONCLUSION: When compared to conventional laparoscopic resection, the NICE procedure is associated with short-term benefits including earlier recovery and less opioid use without increased operative time or increased risk of complications. Multicenter studies are recommended to validate benefits and limitations of this technique.

The success rate of robotic natural orifice intracorporeal anastomosis and transrectal extraction (NICE procedure) in a large cohort of consecutive unselected patients.

BACKGROUND: The Robotic NICE procedure is a total intracorporeal natural orifice approach in which specimen extraction and anastomosis is accomplished without an abdominal wall incision other than the port sites themselves. We aim to present the success rate of the NICE procedure in a large cohort of unselected consecutive patients presenting with colorectal disease using a stepwise and reproducible robotic approach. METHODS: Consecutive patients who presented with benign or malignant disease requiring left-sided colorectal resection and anastomosis between May 2018 and June 2021 were evaluated. Data abstracted included demographic, clinical data, disease features, intervention data, and outcomes data. The main outcome was success rate of Intracorporeal anastomosis (ICA), transrectal extraction of specimen (TRSE), and conversion rate. RESULTS: A total of 306 patients underwent NICE procedure. Diverticulitis was the main diagnosis (64%) followed by colorectal neoplasm (27%). Median operative time was 219 min, and the median estimated blood loss was 50 ml. ICA was achieved in all cases (100%). TRSE was successfully achieved in 95.4% of cases. In 14 patients (4.6%), an abdominal incision was required due to inability to extract a bulky specimen through the rectum. There overall postoperative complications rate was 12.4%. Eight patients (2.6%) experienced postoperative ileus. There were no superficial or deep surgical site infection (SSI). Eleven patients (3.6%) developed organ SSI space including 5 patients with intra-abdominal abscess and 4 patients with anastomotic leak. There was one mortality (0.3%) due to toxic megacolon from resistant Clostridium difficile. The 30-day reoperation rate was 2.9% (n = 9) including six patients presenting with organ space SSI and three patients with postoperative obstruction at the diverting loop ileostomy site. CONCLUSION: The NICE procedure is associated with a very high success rate for both intracorporeal anastomosis and transrectal specimen extraction in a large cohort of unselected patients.

Success rates and outcomes of the robotic NICE procedure across complicated and uncomplicated diverticulitis cases.

INTRODUCTION: We implemented the NICE procedure as a robotic natural orifice colorectal resection utilizing the rectum to extract the specimen and complete an intracorporal anastomosis for diverticulitis in 2018. Although complicated diverticulitis is associated with higher rates of conversion and post-operative morbidity, we hypothesized that the stepwise approach of the NICE procedure can be equally successful in this cohort. We aimed to compare feasibility and outcomes of the NICE procedure for uncomplicated and complicated diverticulitis. METHODS: Consecutive patients presenting with diverticulitis who underwent robotic NICE procedure from May 2018 through June 2021 were included. Cases were stratified into uncomplicated and complicated diverticulitis (fistula, abscess, or stricture). Demographic, clinical, disease, intervention, and outcomes data were analyzed. The main outcome measures were return of bowel function, length of stay, opioid consumption, and postoperative complications. RESULTS: Of a total of 190 patients, those presenting with uncomplicated diverticulitis (53.2%) were compared to those with complicated diverticulitis (47.8%). Uncomplicated diverticulitis had fewer low anterior resections (15.8% vs 49.4%; p < 0.001) and shorter median operative time (186 vs 220 min; p < 0.001). Both cohorts had equal rates of successful intracorporeal anastomosis (100%) and successful transrectal extraction (100% vs 98.9%; p = 0.285). Both cohorts had similar return of bowel function (median 21 h and 18.5; p = 0.149), median length of hospital stay (2 days, p = 0.015) and mean total opioid use (68.4 MME vs 67.3; p = 0.91). There were also no significant differences in overall postoperative complication rate over a 30-day time period (8.9% vs 12.5%; p = 0.44), readmission (6.9% vs 5.6%; p = 0.578) and reoperation (3% vs 4.5%; p = 0.578). CONCLUSION: Despite being inherently more complex and technically challenging, complicated diverticulitis patients have similar success rates and post-operative outcomes compared to uncomplicated diverticulitis patients when undergoing the NICE procedure. These results implicate the benefits of robotic natural orifice techniques may be even more pronounced in complicated diverticulitis patients.

Why can insects not biosynthesize cholesterol?

Two aspects of insect lipid biochemistry differ from the mammalian background. In one aspect, nearly a hundred years ago scientists demonstrated that the polyunsaturated fatty acid (PUFAs), linoleic acid (LA; 18:2n-6) is an essential nutrient in the diets of all mammals that have been studied in that regard. An unknown number of insect species are able to biosynthesize LA de novo. Some species take the biosynthesized LA into fatty acid elongation/desaturation pathways to produce other PUFAs, 18:3n-6, 20:3n-6 and 20:4n-6. A couple of species use the de novo produced LA to biosynthesize prostaglandins and other eicosanoids, short-lived signal moieties that mediate important physiological actions in immunity and reproduction. Insects differ from mammals, also, in their lack of genes that encode enzymes acting in biosynthesis of cholesterol. Insects require dietary cholesterol to meet their cellular, physiological, developmental, and reproductive needs. Looking at a broader view of invertebrate biochemistry, most protostomes lost all or most genes involved in cholesterol biosynthesis. The massive gene loss occurred during the Ediacaran Period, which lasted 96 million years, from the end of the Cryogenian Period (635 million years ago; MYA) to the beginning of the Cambrian Period (538.6 MYA). The key point here is that the inability to biosynthesize cholesterol is not limited to insects; it occured in most protostomes. We address the protostome need and benefits of acquiring exogenous sterols.

Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data.

BACKGROUND: Following the emergency use authorisation of the Pfizer-BioNTech mRNA COVID-19 vaccine BNT162b2 (international non-proprietary name tozinameran) in Israel, the Ministry of Health (MoH) launched a campaign to immunise the 6·5 million residents of Israel aged 16 years and older. We estimated the real-world effectiveness of two doses of BNT162b2 against a range of SARS-CoV-2 outcomes and to evaluate the nationwide public-health impact following the widespread introduction of the vaccine. METHODS: We used national surveillance data from the first 4 months of the nationwide vaccination campaign to ascertain incident cases of laboratory-confirmed SARS-CoV-2 infections and outcomes, as well as vaccine uptake in residents of Israel aged 16 years and older. Vaccine effectiveness against SARS-CoV-2 outcomes (asymptomatic infection, symptomatic infection, and COVID-19-related hospitalisation, severe or critical hospitalisation, and death) was calculated on the basis of incidence rates in fully vaccinated individuals (defined as those for whom 7 days had passed since receiving the second dose of vaccine) compared with rates in unvaccinated individuals (who had not received any doses of the vaccine), with use of a negative binomial regression model adjusted for age group (16-24, 25-34, 35-44, 45-54, 55-64, 65-74, 75-84, and ≥85 years), sex, and calendar week. The proportion of spike gene target failures on PCR test among a nationwide convenience-sample of SARS-CoV-2-positive specimens was used to estimate the prevelance of the B.1.1.7 variant. FINDINGS: During the analysis period (Jan 24 to April 3, 2021), there were 232 268 SARS-CoV-2 infections, 7694 COVID-19 hospitalisations, 4481 severe or critical COVID-19 hospitalisations, and 1113 COVID-19 deaths in people aged 16 years or older. By April 3, 2021, 4 714 932 (72·1%) of 6 538 911 people aged 16 years and older were fully vaccinated with two doses of BNT162b2. Adjusted estimates of vaccine effectiveness at 7 days or longer after the second dose were 95·3% (95% CI 94·9-95·7; incidence rate 91·5 per 100 000 person-days in unvaccinated vs 3·1 per 100 000 person-days in fully vaccinated individuals) against SARS-CoV-2 infection, 91·5% (90·7-92·2; 40·9 vs 1·8 per 100 000 person-days) against asymptomatic SARS-CoV-2 infection, 97·0% (96·7-97·2; 32·5 vs 0·8 per 100 000 person-days) against symptomatic COVID-19, 97·2% (96·8-97·5; 4·6 vs 0·3 per 100 000 person-days) against COVID-19-related hospitalisation, 97·5% (97·1-97·8; 2·7 vs 0·2 per 100 000 person-days) against severe or critical COVID-19-related hospitalisation, and 96·7% (96·0-97·3; 0·6 vs 0·1 per 100 000 person-days) against COVID-19-related death. In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined. 8006 of 8472 samples tested showed a spike gene target failure, giving an estimated prevalence of the B.1.1.7 variant of 94·5% among SARS-CoV-2 infections. INTERPRETATION: Two doses of BNT162b2 are highly effective across all age groups (≥16 years, including older adults aged ≥85 years) in preventing symptomatic and asymptomatic SARS-CoV-2 infections and COVID-19-related hospitalisations, severe disease, and death, including those caused by the B.1.1.7 SARS-CoV-2 variant. There were marked and sustained declines in SARS-CoV-2 incidence corresponding to increasing vaccine coverage. These findings suggest that COVID-19 vaccination can help to control the pandemic. FUNDING: None.

Robotic NICE Procedure Using Handsewn Technique.

INTRODUCTION: In 2018, we described a robotic natural orifice-assisted left-sided colorectal resection with intracorporeal anastomosis and transrectal extraction of the specimen and termed it the natural orifice intracorporeal anastomosis with transrectal extraction procedure. More recently, we have explored the feasibility, safety, and utility of performing total handsewn intracorporeal anastomosis. We present a technical video and initial experience depicting the unique steps to accomplish this procedure with colorectal end-to-end handsewn anastomosis. TECHNIQUE: Twenty natural orifice intracorporeal anastomosis with transrectal extraction procedures with end-to-end handsewn intracorporeal anastomosis were performed. A video depicting the essential steps with 2 variations of the handsewn techniques is presented along with short-term outcomes. RESULTS: The most common indication was complicated diverticulitis followed by rectal cancer and deep infiltrative endometriosis of the rectum. The mean operative time was 235 minutes (99-294 min), and there were no intraoperative complications or conversions. Handsewn end-to-end intracorporeal anastomosis was successful in all patients. Natural orifice transrectal extraction was successful in 17 of 20 (85%) patients. The mean postoperative length of stay was 2.1 days (±1.05 SD). There were 3 major complications. One patient developed a deep surgical site infection, and another patient had an organ space abscess. Both patients required readmission and were treated with antibiotics alone. One patient, who had a diverting ileostomy performed at the time of the index procedure, developed subclinical dehiscence of the anastomosis, which healed without intervention but resulted in a delay in ileostomy reversal. There were no additional readmissions and no reoperations or mortalities. CONCLUSIONS: Robotic natural orifice intracorporeal anastomosis with transrectal extraction procedure and colorectal end-to-end handsewn anastomosis was feasible and safe in this initial series. This technique can be successfully performed in a total intracorporeal manner without the need for an abdominal wall extraction incision or any circular stapling devices.

Real-World Data on Liposomal Bupivacaine and Inpatient Hospital Costs After Colorectal Surgery.

INTRODUCTION: This study compared costs of care among colorectal surgery patients who received liposomal bupivacaine versus those who did not (control) from a health institution perspective. MATERIAL AND METHODS: This pharmacoeconomic evaluation was conducted among adults undergoing open or minimally invasive colorectal resection at an academic medical center from May 2016 to February 2018. Healthcare resource utilization was derived from the electronic health record. Total cost of care (2018 USD) was analyzed using a generalized linear model adjusted for American Society of Anesthesiologists score, enhanced recovery after surgery management, open surgery, opioid use before surgery, height, cancer, and age. The primary analysis used public costs. A sensitivity analysis used internal costs from the hospital to maximize internal validity. RESULTS: Of 486 included patients, 286 (59%) received liposomal bupivacaine. Total cost of care using public costs included perioperative local anesthetics (mean ± standard deviation [SD]: $392 ± 74 liposomal bupivacaine versus $8 ± 13 control), analgesics within 48 h after surgery (mean ± SD: $132 ± 99 liposomal bupivacaine versus $117 ± 127 control), postoperative ileus management (mean ± SD: $5 ± 51 liposomal bupivacaine versus $65 ± 284 control), and hospital length of stay (mean ± SD: $4459 ± 3576 liposomal bupivacaine versus $7769 ± 7082 control). Liposomal bupivacaine was associated with an adjusted absolute difference in total cost of care of -$1435 (95% confidence interval -$2401 to -$470; P = 0.004) using public costs and -$1345 (95% confidence interval -$2215 to -$476; P = 0.002) using internal costs. CONCLUSIONS: Use of liposomal bupivacaine in colorectal surgery was associated with a significant reduction in total cost of care that was predominately driven by reduced costs for hospital stay and postoperative ileus management despite higher medication costs.

A national evaluation of the use and survival impact of adjuvant chemotherapy in Stage II colon cancer from the national cancer database.

AIM: Stage II colon cancers are a heterogeneous category, with controversy over use of adjuvant chemotherapy (AC). Patients with high-risk features may benefit from AC to improve overall survival (OS). Current guidelines do not routinely recommend AC in low-risk cases, but the actual use and benefit on OS in this cohort have not been fully examined on a national scale. We aimed to evaluate the use and impact of AC on OS in low-risk Stage II colon cancer. METHODS: The national cancer database was reviewed for Stage II colon cancers undergoing curative resection (2010-2015). Cases with preoperative radio-chemotherapy or high-risk features were excluded. Cases were stratified into 'AC' and 'no AC' cohorts, and then propensity score matched. Kaplan-Meier and Cox regression analysed OS. The main outcome measures were the incidence and impact of AC on OS in low-risk Stage II colon cancer. RESULTS: Of 39 926 patients evaluated, 8.2% (n = 3275) received AC. Matching resulted in 3275 cases per cohort. AC significantly improved 1-, 3- and 5-year OS versus no AC (P = 0.0017). The 5-year absolute risk reduction was 2.6%, relative risk reduction 12%, with a number needed to treat of 38. In the Cox model, AC remained significantly associated with increased OS (hazard ratio 0.816; 95% CI 0.713-0.934; P < 0.003). CONCLUSIONS: From this dataset, AC was associated with improved OS in low-risk Stage II disease. These findings from a large-scale sample question current guidelines and the need for better risk stratification. Further study with more robust variables is warranted to determine AC best practices.

Colorectal cancer in the 45-to-50 age group in the United States: a National Cancer Database (NCDB) analysis.

BACKGROUND: Amid increasing awareness of early-onset colorectal cancer (CRC), guidelines in the United States (US) recently lowered the recommended routine CRC screening age from 50 to 45 in average-risk individuals. There are little data on the number of patients in this age group diagnosed with CRC prior to these changes. Our objective was to audit the historic CRC case trends and impact of CRC in the 45-to-50-year-old category prior to new screening recommendations. METHODS: Colorectal adenocarcinoma cases in 45-to-50-year-old patients were queried from the NCDB (2004-2017). Cases were stratified by sex, race, and site. The disability-adjusted lost years (DALY) and lost earnings were estimated. The average annual percentage changes (AAPC) of CRC incidence were estimated using jointpoint analysis. The main outcome measures were DALY and lost earnings. Secondary outcome measures were the 2004-2017 AAPC and the cumulative incidence of potential CRC cases in the 45-to-50 cohort through 2030 without guideline changes. RESULTS: 67,442 CRC patients in the 45-to-50 demographic were identified. The CRC burden resulted 899,905 DALY and $17 billion in lost earnings. The 2004-2017 AAPC was 1.6%, with an estimated 13-year increase of 25%. There were sex-, race-, and anatomic site-specific discrepancies with estimated 13-year increases of 30% for males, 110% for American Indian/ Alaska Natives/ Asian American/ Pacific Islander races, and 31% for rectal cancer by 2030. CONCLUSION: CRC has been steadily increasing in the 45-to-50 age group, with tremendous disability and cost ensuing. There is great potential benefit from lowering the recommended routine CRC screening age to 45. Targeted intervention could ensure the most vulnerable segments benefit from the new guidelines, in both reducing the incidence and improving survivorship in CRC patients.

Extracellular Vesicles Protect the Neonatal Lung from Hyperoxic Injury through the Epigenetic and Transcriptomic Reprogramming of Myeloid Cells.

Rationale: Mesenchymal stem/stromal cell (MSC)-small extracellular vesicle (MEx) treatment has shown promise in experimental models of neonatal lung injury. The molecular mechanisms by which MEx afford beneficial effects remain incompletely understood. Objectives: To investigate the therapeutic mechanism of action through assessment of MEx biodistribution and impact on immune cell phenotypic heterogeneity. Methods: MEx were isolated from the conditioned medium of human umbilical cord Wharton's jelly-derived MSCs. Newborn mice were exposed to hyperoxia (HYRX, 75% O2) from birth and returned to room air at Postnatal Day 14 (PN14). Mice received either a bolus intravenous MEx dose at PN4 or bone marrow-derived myeloid cells (BMDMy) pretreated with MEx. Animals were killed at PN4, PN7, PN14, or PN28 to characterize MEx biodistribution or for assessment of pulmonary parameters. The therapeutic role of MEx-educated BMDMy was determined in vitro and in vivo. Measurements and Main Results: MEx therapy ameliorated core histological features of HYRX-induced neonatal lung injury. Biodistribution and mass cytometry studies demonstrated that MEx localize in the lung and interact with myeloid cells. MEx restored the apportion of alveolar macrophages in the HYRX-injured lung and concomitantly suppressed inflammatory cytokine production. In vitro and ex vivo studies revealed that MEx promoted an immunosuppressive BMDMy phenotype. Functional assays demonstrated that the immunosuppressive actions of BMDMy are driven by phenotypically and epigenetically reprogrammed monocytes. Adoptive transfer of MEx-educated BMDMy, but not naive BMDMy, restored alveolar architecture, blunted fibrosis and pulmonary vascular remodeling, and improved exercise capacity. Conclusions: MEx ameliorate hyperoxia-induced neonatal lung injury though epigenetic and phenotypic reprogramming of myeloid cells.

Perfusion Assessment in Left-Sided/Low Anterior Resection (PILLAR III): A Randomized, Controlled, Parallel, Multicenter Study Assessing Perfusion Outcomes With PINPOINT Near-Infrared Fluorescence Imaging in Low Anterior Resection.

BACKGROUND: Indocyanine green fluoroscopy has been shown to improve anastomotic leak rates in early phase trials. OBJECTIVE: We hypothesized that the use of fluoroscopy to ensure anastomotic perfusion may decrease anastomotic leak after low anterior resection. DESIGN: We performed a 1:1 randomized controlled parallel study. Recruitment of 450 to 1000 patients was planned over 2 years. SETTINGS: This was a multicenter trial. PATIENTS: Included patients were those undergoing resection defined as anastomosis within 10 cm of the anal verge. INTERVENTION: Patients underwent standard evaluation of tissue perfusion versus standard in conjunction with perfusion evaluation using indocyanine green fluoroscopy. MAIN OUTCOME MEASURES: Primary outcome was anastomotic leak, with secondary outcomes of perfusion assessment and the rate of postoperative abscess requiring intervention. RESULTS: This study was concluded early because of decreasing accrual rates. A total of 25 centers recruited 347 patients, of whom 178 were randomly assigned to perfusion and 169 to standard. The groups had comparable tumor-specific and patient-specific demographics. Neoadjuvant chemoradiation was performed in 63.5% of perfusion and 65.7% of standard (p > 0.05). Mean level of anastomosis was 5.2 ± 3.1 cm in perfusion compared with 5.2 ± 3.3 cm in standard (p > 0.05). Sufficient visualization of perfusion was reported in 95.4% of patients in the perfusion group. Postoperative abscess requiring surgical management was reported in 5.7% of perfusion and 4.2% of standard (p = 0.75). Anastomotic leak was reported in 9.0% of perfusion compared with 9.6% of standard (p = 0.37). On multivariate regression analysis, there was no difference in anastomotic leak rates between perfusion and standard (OR = 0.845 (95% CI, 0.375-1.905); p = 0.34). LIMITATIONS: The predetermined sample size to adequately reduce the risk of type II error was not achieved. CONCLUSIONS: Successful visualization of perfusion can be achieved with indocyanine green fluoroscopy. However, no difference in anastomotic leak rates was observed between patients who underwent perfusion assessment versus standard surgical technique. In experienced hands, the addition of routine indocyanine green fluoroscopy to standard practice adds no evident clinical benefit. See Video Abstract at http://links.lww.com/DCR/B560. VALORACIN DE LA IRRIGACIN DE LADO IZQUIERDO/RESECCIN ANTERIOR BAJA PILAR III UN ESTUDIO ALEATORIZADO, CONTROLADO, PARALELO Y MULTICNTRICO QUE EVALA LOS RESULTADOS DE LA IRRIGACIN CON PINPOINT IMGENES DE FLUORESCENCIA CERCANA AL INFRARROJO EN LA RESECCIN ANTERIOR BAJA: ANTECEDENTES:Se ha demostrado que la fluoroscopia con verde de indocianina mejora las tasas de fuga anastomótica en ensayos en fases iniciales.OBJETIVO:Nuestra hipótesis es que la utilización de fluoroscopia para asegurar la irrigación anastomótica puede disminuir la fuga anastomótica luego de una resección anterior baja.DISEÑO:Realizamos un estudio paralelo, controlado, aleatorizado 1:1. Se planificó el reclutamiento de 450-1000 pacientes durante 2 años.AMBITO:Multicéntrico.PACIENTES:Pacientes sometidos a resección definida como una anastomosis dentro de los 10cm del margen anal.INTERVENCIÓN:Pacientes que se sometieron a la evaluación estándar de la irrigación tisular contra la estándar en conjunto con la valoración de la irrigación mediante fluoroscopia con verde indocianina.PRINCIPALES VARIABLES EVALUADAS:El principal resultado fue la fuga anastomótica, y los resultados secundarios fueron la evaluación de la perfusión y la tasa de absceso posoperatorio que requirió intervención.RESULTADOS:Este estudio se cerró anticipadamente debido a la disminución de las tasas de acumulación. Un total de 25 centros reclutaron a 347 pacientes, de los cuales 178 fueron, de manera aleatoria, asignados a perfusión y 169 a estándar. Los grupos tenían datos demográficos específicos del tumor y del paciente similares. Recibieron quimio-radioterapia neoadyuvante el 63,5% de la perfusión y el 65,7% del estándar (p> 0,05). La anastomosis estuvo en un nivel promedio de 5,2 + 3,1 cm en perfusión en comparación con 5,2 + 3,3 cm en estándar (p> 0,05). Se reportó una visualización suficiente de la perfusión en el 95,4% de los pacientes del grupo de perfusión. El absceso posoperatorio que requirió tratamiento quirúrgico fue de 5,7% de los perfusion y en el 4,2% del estándar (p = 0,75). Se informó fuga anastomótica en el 9,0% de la perfusión en comparación con el 9,6% del estándar (p = 0,37). En el análisis de regresión multivariante, no hubo diferencias en las tasas de fuga anastomótica entre la perfusión y el estándar (OR 0,845; IC del 95% (0,375; 1,905); p = 0,34).LIMITACIONES:No se logró el tamaño de muestra predeterminado para reducir satisfactoriamente el riesgo de error tipo II.CONCLUSIÓN:Se puede obtener una visualización adecuada de la perfusión con ICG-F. Sin embargo, no se observaron diferencias en las tasas de fuga anastomótica entre los pacientes que se sometieron a evaluación de la perfusión versus la técnica quirúrgica estándar. En manos expertas, agregar ICG-F a la rutina de la práctica estándar no agrega ningún beneficio clínico evidente. Consulte Video Resumen en http://links.lww.com/DCR/B560. (Traducción-Dr Juan Antonio Villanueva-Herrero).

Opioid-Sparing Effect of Liposomal Bupivacaine and Intravenous Acetaminophen in Colorectal Surgery.

BACKGROUND: This study evaluated the opioid-sparing effect of liposomal bupivacaine and intravenous acetaminophen in colorectal surgery. MATERIALS AND METHODS: This study was a retrospective, 2 × 2 factorial cohort conducted at an academic medical center from May 2016 to February 2018. Patients undergoing open or minimally invasive colorectal resection were included. Exclusion criteria were age <18 y, surgery after second hospital day, ostomy, and allergy to acetaminophen, opioids, or bupivacaine. Intraoperative liposomal bupivacaine and intravenous acetaminophen administration within 18 h after surgery were evaluated. The primary outcome was intravenous morphine milligram equivalents administered within 24 h after surgery. A linear regression model adjusted for American Society of Anesthesiologists score, enhanced recovery after surgery management, open surgery, opioid use before surgery, and height was used for the primary analysis. RESULTS: Among 486 included patients, 193 received both liposomal bupivacaine and intravenous acetaminophen, 93 received liposomal bupivacaine only, 104 received intravenous acetaminophen only, and 96 did not receive either. On average, patients received 21 (SD = 31) morphine equivalents over 24 h. Intraoperative liposomal bupivacaine was associated with a reduction of morphine equivalents (adjusted change -11, 95% CI -17 to -6), but intravenous acetaminophen was not (2, 95% CI -3 to 7). Intraoperative liposomal bupivacaine was associated with a reduction of length of stay (adjusted change = -1.2 d, 95% CI -2.1 to -0.3), but intravenous acetaminophen was not (adjusted change = 1.5 d, 95% CI 0.7 to 2.2). CONCLUSIONS: Liposomal bupivacaine was associated with a significant reduction of opioid use within 24 h after colorectal surgery, but intravenous acetaminophen was not.

Robotic natural-orifice IntraCorporeal anastomosis with Extraction (NICE procedure) for complicated diverticulitis.

BACKGROUND: Totally intracorporeal surgery for left-sided resection carries numerous potential advantages by avoiding crossing staple lines and eliminating the need for an abdominal incision. For those with complicated diverticulitis, minimally invasive surgery is known to be technically challenging due to inflamed tissue, distorted pelvic anatomy, and obliterated tissue planes, resulting in high conversion rates. We aim to illustrate the stepwise approach and modifications required to successful complete the robotic Natural-orifice IntraCorporeal anastomosis with transrectal specimen Extraction (NICE) procedure in this cohort. METHODS: Consecutive, elective, unselected patients presenting with complicated diverticulitis defined as fistula, abscess and stricture underwent the NICE procedure over a 24-month period. Demographic and intraoperative data were collected, and video recordings were reviewed and edited on encrypted server. RESULTS: A total of 60 patients (50% female) underwent the NICE procedure for complicated diverticulitis with a mean age of 58.9 years and mean BMI of 30.7 kg/m2. The mean operative time was 231.6 min. All cases (100%) were achieved with intracorporeal anastomosis using a circular stapling device. All but one patient (98.3%) had successful transrectal extraction of the specimen. Forty-four (73%) of the specimens required a specimen-thinning maneuver to successfully extract the specimen and there were no conversions. We identified seven key technical modifications and considerations to facilitate successful completion of the procedure which are illustrated, including early release of the disease, mesentery-sparing dissection, dual instrument control of the mesenteric vasculature, release of the rectal reflection, use of NICE back table, specimen-thinning maneuver, and closure of the rectal cuff. CONCLUSION: We present a stepwise approach with key modifications to successfully achieve totally robotic intracorporeal resection for those presenting with complicated diverticulitis. This approach may help overcome the technical challenges and provide a foundation for reproducible results.

Outbreak of human leptospirosis linked to contaminated water bodies in Northern Israel, June to August 2018.

We report preliminary findings of a large outbreak of human leptospirosis with 36 confirmed/probable and 583 suspected cases from June-August 2018, linked to contaminated water bodies in Northern Israel. There was a travel-associated case in Germany; additional cases are being investigated in other countries. The presumed chain of transmission, implicating wild boar and cattle, raises multiple challenges for risk assessment, risk management and risk communication currently being addressed by a public health response team.

A new perspective on the value of minimally invasive colorectal surgery-payer, provider, and patient benefits.

BACKGROUND: The clinical benefits of minimally invasive surgery (MIS) are proven, but overall financial benefits are not fully explored. Our goal was to evaluate the financial benefits of MIS from the payer's perspective to demonstrate the value of minimally invasive colorectal surgery. METHODS: A Truven MarketScan® claim-based analysis identified all 2013 elective, inpatient colectomies. Cases were stratified into open or MIS approaches based on ICD-9 procedure codes; then costs were assessed using a similar distribution across diagnosis related groups (DRGs). Care episodes were compared for average allowed costs, complication, and readmission rates after adjusting costs for demographics, comorbidities, and geographic region. RESULTS: A total of 4615 colectomies were included-2054 (44.5 %) open and 2561 (55.5 %) MIS. Total allowed episode costs were significantly lower MIS than open ($37,540 vs. $45,284, p < 0.001). During the inpatient stay, open cases had significantly greater ICU utilization (3.9 % open vs. 2.0 % MIS, p < 0.001), higher overall complications (52.8 % open vs. 32.3 % MIS, p < 0.001), higher colorectal-specific complications (32.5 % open vs. 17.9 % MIS, p < 0.001), longer LOS (6.39 open vs. 4.44 days MIS, p < 0.001), and higher index admission costs ($39,585 open vs. $33,183 MIS, p < 0.001). Post-discharge, open cases had significantly higher readmission rates/100 cases (11.54 vs. 8.28; p = 0.0013), higher average readmission costs ($3055 vs. $2,514; p = 0.1858), and greater 30-day healthcare costs than MIS ($5699 vs. $4357; p = 0.0033). The net episode cost of care was $7744/patient greater for an open colectomy, even with similar DRG distribution. CONCLUSIONS: In a commercially insured population, the risk-adjusted allowed costs for MIS colectomy episodes were significantly lower than open. The overall cost difference between MIS and open was almost $8000 per patient. This highlights an opportunity for health plans and employers to realize financial benefits by shifting from open to MIS for colectomy. With increasing bundled payment arrangements and accountable care sharing programs, the cost impact of shifting from open to MIS introduces an opportunity for cost savings.

Ongoing mumps outbreak in Israel, January to August 2017.

In Israel, 262 mumps cases were registered between 1 January and 28 August 2017 despite a vaccine coverage of ≥ 96%. The majority (56.5%) of cases were adolescents and young adults between 10 and 24 years of age. Nearly twice as many cases were reported in males than in females. Sequence information identified genotype G and suggested specific transmission chains in different religious communities, with the Muslim population in Jerusalem being most severely affected.

Transversus abdominis plane blocks: pilot of feasibility and the learning curve.

BACKGROUND: Our goal was to evaluate the learning curve for transversus abdominis plane (TAP) block placement and identify issues that impede successful placement. METHODS: Three novices were prospectively evaluated performing ultrasound-guided TAP blocks in 10 consecutive patients. Operators were assessed on medication knowledge, setup/placement, procedural steps, and performance time. Times were compared to an expert for efficiency and competence. The main outcome measures were procedures needed for competence and variables associated with increased coaching/procedure time. RESULTS: In the 30 patient sample, the mean body mass index (BMI) was 30.9 (standard deviation [SD], 5.79). Fifteen patients were obese (BMI > 30), seven (23.3%) super obese (BMI > 35), and 15 had prior abdominal surgery. The mean setup time was 107.5 s (SD, 87), right-side placement was 131.8 s (SD, 60.3), left-side placement 114.8 s (SD, 40.5), and total time 354 s (SD, 111). By the second attempt, all operators were fluent in the medication and setup. At block 3, operators 1 and 3 reached competence in performance time; by block 4, all three operators reached time competence. After reaching competence, outliers in procedure times were only experienced for extremes in BMI (<20 and >35). Additional coaching was needed in four patients with prior abdominal surgery to decipher the correct planes. CONCLUSIONS: Based on our pilot, by four attempts, novices reach appropriate speeds with progressively less coaching to safely and efficiently place TAP blocks. Extremes of BMI and prior abdominal surgery impact procedural time and may required additional coaching to facilitate placement. Given the promising results, further work on developing best practices for education and implementation is warranted.