Reducing the neurosurgical waiting list burden: is it a futile endeavour?

BACKGROUND: Cancellation of elective operations during the COVID-19 pandemic has led to a significant increase in the number of patients waiting for treatment. In neurosurgery, treatment for spinal diseases, in particular, has been disproportionately delayed. We aim to describe the waiting list burden at our institution and forecast the time and theatre capacity required to return to pre-pandemic levels. METHODS: A retrospective evaluation of the waiting list records (both cranial and spinal), from January 2015-October 2022, inclusive, was conducted at a high-volume neurosciences centre. The average monthly decrease in the waiting list was calculated for the months since the waiting list was noted to fall consistently during or after the pandemic, as applicable. Five different scenarios were modelled to identify the time required to reduce the waiting list to the pre-pandemic level of December 2019. Data collection and analyses were performed on Excel (Microsoft). RESULTS: At the pre-pandemic threshold (December 2019), 782 patients were on the waiting list. Between January 2015-January 2020, inclusive, an average of 673 patients were on the waiting list but this has doubled over the subsequent months to a peak of 1388 patients in December 2021. Between December 2021-October 2022, on average, the waiting list reduced by 18 per month. At the current rate of change, the waiting list would fall to the pre-pandemic level by October 2024, an interval of 24 months. A seven-day service would require 18 months to clear the backlog. Doubling or tripling the current rate of change would require 12 months and 8 months, respectively. CONCLUSIONS: Pre-existing, pandemic-related, and new NHS-wide challenges continue to have negative influences on reducing the backlog. Proposals for surgical hubs to tackle this carry the risks of removing staff from hospitals which cannot avoid emergency/urgent operating thereby further reducing those institutions' capacity to undertake elective work.

Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults

The SARS-CoV-2 Omicron variant has challenged the control of the COVID-19 pandemic even in highly vaccinated countries. While a second booster of mRNA vaccines improved the immunity against SARS-CoV-2, the humoral and cellular responses induced by a second booster of an inactivated SARS-CoV-2 vaccine have not been studied. In the context of a phase 3 clinical study, we report that a second booster of CoronaVac(R) increased the neutralizing response against the ancestral virus yet showed poor neutralization against the Omicron variant. Additionally, isolated PBMCs displayed equivalent activation of specific CD4+ T cells and IFN-{gamma} production when stimulated with a mega-pool of peptides derived from the spike protein of the ancestral virus or the Omicron variant. In conclusion, a second booster dose of CoronaVac(R) does not improve the neutralizing response against the Omicron variant compared with the first booster dose, yet it helps maintaining a robust spike-specific CD4+ T cell response.

Differential immune response induced by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial

BackgroundThe development of vaccines to control the COVID-19 pandemic progression is a worldwide priority. CoronaVac(R) is an inactivated SARS-CoV-2 vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. MethodsThis study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged [≥]18 years. Volunteers received two doses of CoronaVac(R) separated by two (0-14 schedule) or four weeks (0-28 schedule). 2,302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. ResultsBoth schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern between schedules. Stimulation of PBMCs with MPs induced the secretion of IFN-{gamma} and the expression of activation induced markers for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-{gamma} secretion. ConclusionsImmunization with CoronaVac(R) in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule. FundingMinistry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile. Clinical trial numberNCT04651790. summaryTwo immunization schedules were evaluated for the inactivated SARS-CoV-2 vaccine, Coronavac(R), with two doses of the vaccine separated by two or four weeks. We compared humoral and cellular immune responses, showing they are mostly similar, with differences in neutralization capacities.

Safety and efficacy of two immunization schedules with an inactivated SARS-CoV-2 vaccine in adults. A randomized non-inferiority clinical trial.

BackgroundSeveral vaccines have been developed to control the COVID-19 pandemic. CoronaVac(R) (Sinovac Life Sciences), an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity in previous studies, preventing severe COVID-19 cases. We further investigated the safety and efficacy of two immunization schedules of CoronaVac(R) in a non-inferiority trial in healthy adults. MethodsThis is a multi-center and randomized clinical trial. Healthy adults were enrolled at eight centers in Chile. Participants were randomly assigned to two vaccination schedules, receiving two doses with either 14 (0-14) or 28 (0-28) days between each. 2302 participants were vaccinated. The primary safety and efficacy endpoints were solicited adverse events (AE) within 7 days after each dose and compared the number of cases of SARS-CoV-2 infection 14 days after the second dose between schedules, respectively. FindingsThe most frequent local AE was pain at the injection site, which was less frequent in participants aged [≥]60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. The remaining AEs were minor allergic reactions and fever. Most AEs were mild and transient. There were no significant differences for local and systemic AE between schedules. No anaphylactic reactions or vaccine-related severe AEs were observed. 58 COVID-19 cases were confirmed, and all but two of them were mild. No differences were observed in protection between schedules. InterpretationCoronaVac(R) is safe, especially in [≥]60 years-old participants. Both schedules protected against COVID-19 hospitalizations. FundingMINSAL, Chile, CPC & IMII, Chile. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSCoronaVac(R) (an inactivated SARS-CoV-2 vaccine) was approved on June 1st, 2021, by the WHO for its use in humans. Sinovac Life Sciences generated this vaccine in China and conducted phase 1/2 trials. Good safety, efficacy, and immunogenicity profiles were reported. The results from this study led to the use of CoronaVac(R) in other countries, such as Brazil, Turkey, and Chile, with phase 3 trials being held on them. Added-value of this studyThis work compares the safety and efficacy of two immunization schedules with CoronaVac(R), with each dose administrated two or four weeks after the first dose on healthy Chilean adults. To date, no studies showing the safety and efficacy of these two immunization schedules with CoronaVac(R) in healthy adults in a population other than the Chinese have been published. We show that CoronaVac(R) is safe and prevents hospitalization due to COVID-19 in both immunization schedules. No differences were found in the incidence of adverse events between both schedules, and no related severe adverse events were reported. These results give further insight into the immune response induced by CoronaVac(R) and are relevant when deciding on the immunization schedule chosen for vaccination. Implications of all the available evidenceThe data reported here show that using either immunization schedule with two doses of CoronaVac(R) protects against SARS-CoV-2. The data also indicate that CoronaVac(R) does not induce severe adverse events in either immunization schedule, and the adverse events registered are mild and transient, confirming the safety of this vaccine.

A pumpless artificial lung without systemic anticoagulation: The Nitric Oxide Surface Anticoagulation system.

BACKGROUND: Artificial lungs have the potential to serve as a bridge to transplantation or recovery for children with end-stage lung disease dependent on extracorporeal life support, but such devices currently require systemic anticoagulation. We describe our experience using the novel Nitric Oxide (NO) Surface Anticoagulation (NOSA) system-an NO-releasing circuit with NO in the sweep gas-with the Pediatric MLung-a low-resistance, pumpless artificial lung. METHODS: NO flux testing: MLungs (n = 4) were tested using veno-venous extracorporeal life support in a sheep under anesthesia with blood flow set to 0.5 and 1 L/min and sweep gas blended with 100 ppm NO at 1, 2, and 4 L/min. NO and NO2 were measured in the sweep and exhaust gas to calculate NO flux across the MLung membrane. Pumpless implants: Sheep (20-100 kg, n = 3) underwent thoracotomy and cannulation via the pulmonary artery (device inflow) and left atrium (device outflow) using cannulae and circuit components coated with an NO donor (diazeniumdiolated dibutylhexanediamine; DBHD-N2O2) and argatroban. Animals were connected to the MLung with 100 ppm NO in the sweep gas under anesthesia for 24 h with no systemic anticoagulation after cannulation. RESULTS: NO flux testing: NO flux averaged 3.4 ± 1.0 flux units (x10-10 mol/cm2/min) (human vascular endothelium: 0.5-4 flux units). Pumpless implants: 3 sheep survived 24 h with patent circuits. MLung blood flow was 716 ± 227 mL/min. Outlet oxygen saturation was 98.3 ± 2.6%. Activated clotting time was 151±24 s. Platelet count declined from 334,333 ± 112,225 to 123,667 ± 7,637 over 24 h. Plasma free hemoglobin and leukocyte and platelet activation did not significantly change. CONCLUSIONS: The NOSA system provides NO flux across a gas-exchange membrane of a pumpless artificial lung at a similar rate as native vascular endothelium and achieves effective local anticoagulation of an artificial lung circuit for 24 h.

A booster dose of an inactivated vaccine increases neutralizing antibodies and T cell responses against SARS-CoV-2

BackgroundCoronaVac(R) is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization. Previous studies reported increased levels of neutralizing antibodies and specific T cells two- and four-weeks after two doses of CoronaVac(R), but the levels of neutralizing antibodies are reduced at six to eight months after two doses. Here we report the effect of a booster dose of CoronaVac(R) on the anti-SARS-CoV-2 immune response generated against variants of concern (VOC) Delta and Omicron in adults participating in a phase 3 clinical trial in Chile. MethodsVolunteers immunized with two doses of CoronaVac(R) in a four-week interval received a booster dose of the same vaccine between twenty-four and thirty weeks after the 2nd dose. Four weeks after the booster dose, neutralizing antibodies and T cell responses were measured. Neutralization capacities and T cell activation against VOC Delta and Omicron were detected at four weeks after the booster dose. FindingsWe observed a significant increase in neutralizing antibodies at four weeks after the booster dose. We also observed an increase in CD4+ T cells numbers over time, reaching a peak at four weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2 specific T cells induced by the booster showed activity against VOC Delta and Omicron. InterpretationOur results show that a booster dose of CoronaVac(R) increases the anti-SARS-CoV-2 humoral and cellular immune responses in adults. Immunity induced by a booster dose of CoronaVac(R) is active against VOC, suggesting an effective protection.

Impact of lymph nodal stage on gallbladder cancer survival after extended cholecystectomy and adjuvant radiochemotherapy: long-term results from an oncology institute, Chile.

INTRODUCTION: Gallbladder cancer (GBC) is one of the most important causes of cancer death in Chile. MATERIALS AND METHODS: A retrospective review of 103 patients with a diagnosis of GBC who were treated with surgery and adjuvant radiochemotherapy (RT-CT) was carried out at the Oncological Institute of Viña del Mar, Chile. Of these, 56 underwent surgery with oncological criteria, in which the impact of lymph node involvement and prognostic factors for survival were analysed. RESULTS: The median follow-up was 47.5 months. The 5-year survival of the patients operated on with oncological surgery was 55%, and for those resected without oncological criteria, it was 32% (p = 0.02). Regarding the impact of lymph node involvement, 5-year overall survival (OS) in patients with compromised lymph nodes was 32% versus 68% for patients without compromised lymph nodes (p = 0.006). Five-year OS in patients without involved nodes, with 1 involved node or with>1 involved node was 68%, 44% and 12%, respectively (p = 0.0002). The N ratio was grouped in 0, <10% and ≥10%. Five-year OS was 71%, 0% and 24%, respectively (p = 0.003). There was no evidence of differences in survival with respect to the number of lymph nodes studied. CONCLUSION: Our data provide information regarding the importance of lymph node involvement in patients with GBC undergoing surgery with oncological criteria and adjuvant RT-CT. In the absence of randomised studies, it is suggested to have a more aggressive therapeutic approach in those patients with two or more involved nodes or with a lymph node ratio >10%.

Interim Report: Safety And Immunogenicity Of An Inactivated Vaccine Against Sars-Cov-2 In Healthy Chilean Adults In A Phase 3 Clinical Trial

BackgroundThe ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile. MethodsThis is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov (NCT04651790). FindingsThe recruitment of participants occurred between November 27th, 2020, until January 9th, 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were [≥]60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the [≥]60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the [≥]60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The [≥]60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants [≥]60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-{gamma} upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity. InterpretationImmunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-{gamma}, upon recognition of SARS-CoV-2 antigens. FundingMinistry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

Neurosurgical Referral Patterns During the Coronavirus Disease 2019 Pandemic: A United Kingdom Experience.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a severe respiratory viral illness that has spread rapidly across the world. However, the United Kingdom has been particularly affected. Evidence has suggested that stroke, cardiac, and spinal presentations decreased during the pandemic as the public avoided seeking care. The effect on neurosurgical presentations and referrals during COVID-19 is unclear. Our aim, therefore, was to describe the referral patterns to a high-volume neurosurgical department in the United Kingdom during the COVID-19 pandemic. METHODS: Electronic referrals were identified from the referrals database from January 1, 2020 to May 31, 2020, inclusive, with January used as the baseline. The demographic data and referral diagnoses were captured on Excel (Microsoft, Redmond, Washington, USA). Statistical analyses were performed using SPSS, version 22 (IBM Corp., Armonk, New York, USA). Differences between referral volumes were evaluated using χ2 goodness-of-fit tests. RESULTS: A total of 2293 electronic referrals had been received during the study period. The median age was 63 years. Overall, the referrals had decreased significantly in volume during the study period [χ2(4) = 60.95; P < 0.001]. We have described the patterns in the daily referrals as the pandemic progressed. The reduction in the volume of referrals for degenerative spine cases and traumatic brain injuries was statistically significant (P < 0.001). CONCLUSIONS: The referrals for degenerative spine and traumatic brain injuries decreased significantly during the pandemic, which can be explained by the lower vehicular traffic and patient avoidance of healthcare services, respectively. The risk of neurological deterioration and increased morbidity and mortality, as a consequence, is of concern, and neurosurgeons worldwide should consider the optimal strategies to mitigate these risks as the pandemic eases.

[Complicated acute appendicitis as intercurrent disease in patient with advanced gastric cancer]. / Apendicitis complicada como enfermedad intercurrente en pacientes con cáncer gástrico avanzado.

We report a case of a male 64 years old with acute abdomen who was operated with the presumptive diagnosis of complicated acute appendicitis. However the patient had black stools for two months, associated with epigastric pain. Endoscopic diagnosis was: Advanced Gastric Cancer: Borrmann II. Histology was informed as: Infiltrating adenocarcinoma intestinal type middlingly differentiated. Surgery findings were: peritonitis with perforated appendicitis in its base: Free coprolites and carcinomatosis. Histology was reported as: ulcerated mucous in caecal appendix, necrosis and perforation of the muscular wall in the base. Mesentery samples were informed with fat tissue involvement by infiltration of tubular adenocarcinoma.middlingly differentiated, suitable with primary gastric cancer.