Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course.

Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential.

Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein.

Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2' site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization, and, similar to fp.006 and hr2.016, protects mice expressing human angiotensin-converting enzyme 2 against infection when present as a bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants.

Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2.

Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera , including the nine human coronaviruses, through recognition of a conserved motif that includes the S2' site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae , including SARS-CoV-2 variants. One sentence summary: Broadly cross-reactive antibodies that protect from SARS-CoV-2 variants are revealed by virus coldspot-driven discovery.

Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course.

Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 infection and autoimmune disorders, but they target different chemokines than those in COVID-19. Monoclonal antibodies derived from COVID- 19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID-19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential. One-Sentence Summary: Naturally arising anti-chemokine antibodies associate with favorable COVID-19 and predict lack of long COVID.

Primary jejunogastric intussusception: A case report and review of the literature.

INTRODUCTION: Jejunogastric intussusception following gastric surgery is a rare complication that, if not diagnosed early, can have catastrophic outcomes. PRESENTATION OF CASE: We have reported a case, never described previously, of an acute spontaneous retrograde JGI, presenting with obstruction and hematemesis, in a 70-year-old woman who has never, previously, undergone abdominal surgery. DISCUSSION: As in all cases of intestinal intussusception, early diagnosis is important for acute JGI as mortality rates increase from 10% when the intervention occurs within 48 h. to 50% if treatment is delayed for 96 h. The diagnosis of JGI can be determined with many imaging studies, such as endoscopy, ultrasonography (US), barium stadium and CT scan. Although JGI, up to now, has been described as a rare complication after any type of gastric surgery, this disease must, however, be suspected also in patients who have never undergone abdominal surgery, if they present with non-sedable abdominal pain associated with signs of high intestinal obstruction and hematemesis. CONCLUSION: Our hope is to add to the available literature to aid physicians in their diagnostic work-up and in developing management plans for similar cases occurring in the future.

Gangrenous appendicitis in Amyand's hernia: Surgical approach under local anesthesia. Case report and review of the literature.

INTRODUCTION AND IMPORTANCE: Amyand hernia is a rare disease seen in approximatively 1% of all hernias, complications of it, like acute appendicitis, or perforated appendicitis are even more rare, about 0.1%. Its diagnosis is very difficult in the preoperative period: it is usually an incidental finding. CASE PRESENTATION: We report an unusual case of perforated gangrenous appendicitis with peri-appendicular abscess occurring in an irreducible Amyand's hernia. An 80-year-old male, with chronic obstructive disease and pulmonary emphysema, atrial fibrillation, acute myocardial infarction, underwent urgent surgery, under local anesthesia, for right incarcerated inguinoscrotal hernia. He was found to have a perforated gangrenous appendicitis with peri-appendicular abscess within a right indirect inguinal hernia sac. Appendicectomy and Bassini's hernia repair were performed under local anesthesia without any complications. CLINICAL DISCUSSION: The treatment of Amyand's hernia is not standardized. The current generally accepted algorithm for Amyand's hernia is essentially contingent on the appendix's condition within the hernia sac. CONCLUSION: Appendectomy and primary herniorrhaphy, under local anesthesia, for type 3 of Amyand's hernia, is a safe procedure and easy to perform and, if confirmed by further study, could be part of every surgeon's knowledge.

Laparoscopic vs. open approach for colorectal cancer: evolution over time of minimal invasive surgery.

BACKGROUND: In the late '80s the successes of the laparoscopic surgery for gallbladder disease laid the foundations on the modern use of this surgical technique in a variety of diseases. In the last 20 years, laparoscopic colorectal surgery had become a popular treatment option for colorectal cancer patients. DISCUSSION: Many studies emphasized on the benefits stating the significant advantages of the laparoscopic approach compared with the open surgery of reduced blood loss, early return of intestinal motility, lower overall morbidity, and shorter duration of hospital stay, leading to a general agreement on laparoscopic surgery as an alternative to conventional open surgery for colon cancer. The reduced hospital stay may also decrease the cost of the laparoscopic surgery for colorectal cancer, despite th higher operative spending compared with open surgery. The average reduction in total direct costs is difficult to define due to the increasing cost over time, making challenging the comparisons between studies conducted during a time range of more than 10 years. However, despite the theoretical advantages of laparoscopic surgery, it is still not considered the standard treatment for colorectal cancer patients due to technical limitations or the characteristics of the patients that may affect short and long term outcomes. CONCLUSIONS: The laparoscopic approach to colectomy is slowly gaining acceptance for the management of colorectal pathology. Laparoscopic surgery for colon cancer demonstrates better short-term outcome, oncologic safety, and equivalent long-term outcome of open surgery. For rectal cancer, laparoscopic technique can be more complex depending on the tumor location. The advantages of minimally invasive surgery may translate better care quality for oncological patients and lead to increased cost saving through the introduction of active enhanced recovery programs which are likely cost-effective from the perspective of the hospital health-care providers.

Laparoscopic-assisted versus open surgery for colorectal cancer: short- and long-term outcomes comparison.

BACKGROUND: Despite the theoretical advantages of laparoscopic surgery, it is still not considered the standard treatment for colorectal cancer patients because of criticism concerning oncologic stability. This study aimed at examining the short- and long-term follow-up results of laparoscopic surgery versus open surgery for colorectal cancer and at investigating clinical outcomes, oncologic safety, and any potential advantages of laparoscopic colorectal cancer resection. SUBJECTS AND METHODS: We retrospectively analyzed a database containing the information about patients who underwent surgery for stage I-III colorectal cancer from January 2004 to January 2012 at our institution. RESULTS: The patients who underwent the laparoscopic-assisted procedure showed a significantly faster recovery than those who underwent open surgery, namely, less time to first passing flatus (P=.041), time of first bowel motion (P=.04), time to resume normal diet (P=.043), and time to walk independently (P=.031). Laparoscopic colorectal surgery caused less pain for patients, leading to lower need of analgesic (P=.002) and less hospital recovery time (P=.034), compared with patients who underwent open surgery. No differences were found in 3- and 5-year overall and disease-free survival rates. CONCLUSIONS: Our results suggested that the laparoscopic approach was as safe as the open alternative. Laparoscopic-assisted surgery has been shown to be a favorable surgical option with better short-term outcomes and similar long-term oncological control compared with open resection.