Purpose Laparoscopic partial nephrectomy is an increasingly performed, minimally invasive alternative to open partial nephrectomy. We compared early postoperative outcomes in 1,800 patients ...undergoing open partial nephrectomy by experienced surgeons with the initial experience with laparoscopic partial nephrectomy in patients with a single renal tumor 7 cm or less. Materials and Methods Data on 1,800 consecutive open or laparoscopic partial nephrectomies were collected prospectively or retrospectively in tumor registries at 3 large referral centers. Demographic, intraoperative, postoperative and followup data were compared between the 2 groups. Results Compared to the laparoscopic partial nephrectomy group of 771 patients the 1,028 undergoing open partial nephrectomy were a higher risk group with a greater percent presenting symptomatically with decreased performance status, impaired renal function and tumor in a solitary functioning kidney (p <0.0001). More tumors in the open partial nephrectomy group were more than 4 cm and centrally located and more proved to be malignant (p <0.0001 and 0.0003, respectively). Based on multivariate analysis laparoscopic partial nephrectomy was associated with shorter operative time (p <0.0001), decreased operative blood loss (p <0.0001) and shorter hospital stay (p <0.0001). The chance of intraoperative complications was comparable in the 2 groups. However, laparoscopic partial nephrectomy was associated with longer ischemia time (p <0.0001), more postoperative complications, particularly urological (p <0.0001), and an increased number of subsequent procedures (p <0.0001). Renal functional outcomes were similar 3 months after laparoscopic and open partial nephrectomy with 97.9% and 99.6% of renal units retaining function, respectively. Three-year cancer specific survival for patients with a single cT1N0M0 renal cell carcinoma was 99.3% and 99.2% after laparoscopic and open partial nephrectomy, respectively. Conclusions Early experience with laparoscopic partial nephrectomy is promising. Laparoscopic partial nephrectomy offered the advantages of less operative time, decreased operative blood loss and a shorter hospital stay. When applied to patients with a single renal tumor 7 cm or less, laparoscopic partial nephrectomy was associated with additional postoperative morbidity compared to open partial nephrectomy. However, equivalent functional and early oncological outcomes were achieved.
The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms ...about the effectiveness of current medical countermeasures. To address this concern, we measured the neutralization of the Omicron BA.1 variant pseudovirus by postvaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex was associated with the differences in postvaccination antibody responses. We also evaluated 18 clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants.
The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We ...measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.
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•Antigenic cartography of convalescent sera shows BA.1 as the most distinct variant•SARS-CoV-2 convalescent or vaccinee sera distinguish BA.1 and BA.4/BA.5 variants•Third vaccine boosts BA.1 and BA.2 neutralization more than BA.2.12.1 and BA.4/BA.5•BA.1 infection after two or three vaccinations broadens neutralization similarly
Wang et al. show that SARS-CoV-2 Omicron BA.1 or BA.1.1 infection after a second or third mRNA COVID-19 vaccination broadens neutralizing antibody responses to all variants, including Omicron, more than three vaccinations alone. BA.2.12.1 and BA.4/BA.5 evade neutralization more than BA.1 and BA.2 after three vaccinations or Omicron infection post-vaccination.
Abstract
Little is known about severe acute respiratory syndrome coronavirus 2 “vaccine-breakthrough” infections (VBIs). Here we characterize 24 VBIs in predominantly young healthy persons. While ...none required hospitalization, a proportion endorsed severe symptoms and shed live virus as high as 4.13 × 103 plaque-forming units/mL. Infecting genotypes included both variant-of-concern (VOC) and non-VOC strains.
Abstract Background Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory ...profiles may improve clinical prognostication and trial endpoints. Methods This analysis included 1988 SARS-CoV-2 positive U.S. Military Health System beneficiaries who had quantitative post–COVID symptom scores. Among participants who reported moderate-to-severe symptoms on surveys collected 6 months post-SARS-CoV-2 infection, principal component analysis followed by k-means clustering identified distinct clusters of symptoms. Results Three symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster. Individuals within the sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization than those with no/mild symptoms at 6 months post-infection. Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking and elevated ICAM-1 concentrations to sensory symptoms. Conclusions We identified three distinct symptom-based PCC phenotypes with specific clinical risk factors and early post-infection inflammatory predictors. With further validation and characterization, this framework may allow more precise classification of PCC cases and potentially improve the diagnosis, prognostication, and treatment of PCC.
ABSTRACT
Introduction
Tele-critical care (TCC) has improved outcomes in civilian hospitals and military treatment facilities (MTFs). Tele-critical care has the potential to concurrently support MTFs ...and operational environments and could increase capacity and capability during mass casualty events. TCC services distributed across multiple hub sites may flexibly adapt to rapid changes in patient volume and complexity to fully optimize resources. Given the highly variable census in MTF intensive care units (ICU), the proposed TCC solution offers system resiliency and redundancy for garrison, operational, and mass casualty needs, while also maximizing return on investment for the Defense Health Agency.
Materials and Methods
The investigators piloted simultaneous TCC support to the MTF during three field exercises: (1) TCC concurrently monitored the ICU during a remote mass casualty exercise: the TCC physician monitored a high-risk ICU patient while the nurse monitored 24 simulated field casualties; (2) TCC concurrently monitored the garrison ICU and a remote military medical field exercise: the physician provided tele-mentoring during prolonged field care for a simulated casualty, and the nurse provided hospital ICU TCC; (3) the TCC nurse simultaneously monitored the ICU while providing reach-back support to field hospital nurses training in a simulation scenario.
Results
TCC proved feasible during multiple exercises with concurrent tele-mentoring to different care environments including physician and nurse alternating operational and hospital support roles, and an ICU nurse managing both simultaneously. ICU staff noted enhanced quality and safety of bedside care. Field exercise participants indicated TCC expanded multipatient monitoring during mass casualties and enhanced novice caregiver procedural capability and scope of patient complexity.
Conclusions
Tele-critical care can extend critical care services to anywhere at any time in support of garrison medicine, operational medicine, and mass casualty settings. An interoperable, flexibly staffed, and rapidly expandable TCC network must be further developed given the potential for large casualty volumes to overwhelm a single TCC provider with multiple duties. Lessons learned from development of this capability should have applicability for managing military and civilian mass casualty events.
Chronic neuropsychological sequelae following SARS-CoV-2 infection, including depression, anxiety, fatigue, and general cognitive difficulties, are a major public health concern. Given the potential ...impact of long-term neuropsychological impairment, it is important to characterize the frequency and predictors of this post-infection phenotype.
The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal study assessing the impact of SARS-CoV-2 infection in U.S. Military Healthcare System (MHS) beneficiaries, i.e. those eligible for care in the MHS including active duty servicemembers, dependents, and retirees. Four broad areas of neuropsychological symptoms were assessed cross-sectionally among subjects 1-6 months post-infection/enrollment, including: depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), fatigue (PROMIS® Fatigue 7a), and cognitive function (PROMIS® Cognitive Function 8a and PROMIS® Cognitive Function abilities 8a). Multivariable Poisson regression models compared participants with and without SARS-CoV-2 infection history on these measures, adjusting for sex, ethnicity, active-duty status, age, and months post-first positive or enrollment of questionnaire completion (MPFP/E); models for fatigue and cognitive function were also adjusted for depression and anxiety scores.
The study population included 2383 participants who completed all five instruments within six MPFP/E, of whom 687 (28.8%) had at least one positive SARS-CoV-2 test. Compared to those who had never tested positive for SARS-CoV-2, the positive group was more likely to meet instrument-based criteria for depression (15.4% vs 10.3%, p<0.001), fatigue (20.1% vs 8.0%, p<0.001), impaired cognitive function (15.7% vs 8.6%, p<0.001), and impaired cognitive function abilities (24.3% vs 16.3%, p<0.001). In multivariable models, SARS-CoV-2 positive participants, assessed at an average of 2.7 months after infection, had increased risk of moderate to severe depression (RR: 1.44, 95% CI 1.12-1.84), fatigue (RR: 2.07, 95% CI 1.62-2.65), impaired cognitive function (RR: 1.64, 95% CI 1.27-2.11), and impaired cognitive function abilities (RR: 1.41, 95% CI 1.15-1.71); MPFP/E was not significant.
Participants with a history of SARS-CoV-2 infection were up to twice as likely to report cognitive impairment and fatigue as the group without prior SARS-CoV-2 infection. These findings underscore the continued importance of preventing SARS-CoV-2 infection and while time since infection/enrollment was not significant through 6 months of follow-up, this highlights the need for additional research into the long-term impacts of COVID-19 to mitigate and reverse these neuropsychological outcomes.
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