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Infections that are unusually severe or caused by opportunistic pathogens are a hallmark of primary immunodeficiency (PID). Anti-cytokine autoantibodies (ACA) are an emerging cause of acquired immunodeficiency mimicking PID. Nocardia spp. are Gram-positive bacteria generally inducing disseminated infections in immunocompromised patients, but seldom also occurring in apparently immunocompetent hosts. Anti-GM-CSF autoantibodies are associated with autoimmune pulmonary alveolar proteinosis (PAP). In those patients, an increased incidence of disseminated nocardiosis and cryptococcosis has been observed. It is unclear whether the PAP or the autoantibodies predispose to the infection. We report an apparently immunocompetent woman presenting with disseminated nocardiosis without any evidence of PAP. Clinical data and radiological images were retrospectively collected. Lymphocyte populations were analyzed by flow cytometry. Anti-GM-CSF autoantibodies were measured by ELISA. A 55-year-old otherwise healthy woman presented with cerebral and pulmonary abscesses. Personal and familial history of infections or autoimmunity were negative. After extensive examinations, a final diagnosis of disseminated nocardiosis was made. Immunologic investigations including neutrophilic function and IFN-γ/IL-12 circuitry failed to identify a PID. Whole-exome sequencing did not find pathogenic variants associated with immunodeficiency. Serum anti-GM-CSF autoantibodies were positive. There were no clinical or instrumental signs of PAP. Trimethoprim-sulfamethoxazole and imipenem were administered, with progressive improvement and recovery of the infectious complication. We identified anti-GM-CSF autoantibodies as the cause of disseminated nocardiosis in a previously healthy and apparently immunocompetent adult. This case emphasizes the importance of including ACA in the differential diagnosis of PID, especially in previously healthy adults. Importantly, anti-GM-CSF autoantibodies can present with disseminated nocardiosis without PAP. [ABSTRACT FROM AUTHOR]

Association of advanced age, neoplastic disease and immunocompromission (IC) may lead to surgical emergencies. Few data exist about this topic. Present study reports the preliminary data from the WIRES-T trial about patients managed for colorectal neoplastic emergencies in immunocompromised patients. The required data were taken from a prospective observational international register. The study was approved by the Ethical Committee with approval n. 17575; ClinicalTrials.gov Identifier: NCT03643718. 839 patients were collected; 753 (80.7%) with mild–moderate IC and 86 (10.3%) with severe. Median age was 71.9 years and 73 years, respectively, in the two groups. The causes of mild–moderate IC were reported such malignancy (753–100%), diabetes (103–13.7%), malnutrition (26–3.5%) and uremia (1–0.1%), while severe IC causes were steroids treatment (14–16.3%); neutropenia (7–8.1%), malignancy on chemotherapy (71–82.6%). Preoperative risk classification were reported as follow: mild–moderate: ASA 1–14 (1.9%); ASA 2–202 (26.8%); ASA 3–341 (45.3%); ASA 4–84 (11.2%); ASA 5–7 (0.9%); severe group: ASA 1-1 patient (1.2%); ASA 2–16 patients (18.6%); ASA 3–41 patients (47.7%); ASA 4–19 patients (22.1%); ASA 5–3 patients (3.5%); lastly, ASA score was unavailable for 105 cases (13.9%) in mild–moderate group and in 6 cases (6.9%) in severe group. All the patients enrolled underwent urgent/emergency surgery Damage control approach with open abdomen was adopted in 18 patients. Mortality was 5.1% and 12.8%, respectively, in mild–moderate and severe groups. Long-term survival data: in mild–moderate disease-free survival (median, IQR) is 28 (10–91) and in severe IC, it is 21 (10–94). Overall survival (median, IQR) is 44 (18–99) and 26 (20–90) in mild–moderate and severe, respectively; the same is for post-progression survival (median, IQR) 29 (16–81) and 28, respectively. Univariate and multivariate analyses showed as the only factor influencing mortality in mild–moderate and severe IC is the ASA score. Colorectal neoplastic emergencies in immunocompromised patients are more frequent in elderly. Sigmoid and right colon are the most involved. Emergency surgery is at higher risk of complication and mortality; however, management in dedicated emergency surgery units is necessary to reduce disease burden and to optimize results by combining oncological and acute care principles. This approach may improve outcomes to obtain clinical advantages for patients like those observed in elective scenario. Lastly, damage control approach seems feasible and safe in selected patients. [ABSTRACT FROM AUTHOR]

Background: The surgical treatment for perforated peptic ulcers (PPUs) can be safely performed laparoscopically. This study aimed to compare the outcomes of patients who received different surgical approaches for PPU and to identify the predictive factors for conversion to open surgery. Methods: This retrospective study analyzed patients treated for PPUs from 2002 to 2020. Three groups were identified: a complete laparoscopic surgery group (LG), a conversion to open group (CG), and a primary open group (OG). After univariate comparisons, a multivariate analysis was conducted to identify the predictive factors for conversion. Results: Of the 175 patients that underwent surgery for PPU, 104 (59.4%) received a laparoscopic-first approach, and 27 (25.9%) required a conversion to open surgery. Patients treated directly with an open approach were older (p < 0.0001), had more comorbidities (p < 0.0001), and more frequently had a previous laparotomy (p = 0.0001). In the OG group, in-hospital mortality and ICU need were significantly higher, while the postoperative stay was longer. Previous abdominal surgery (OR 0.086, 95% CI 0.012–0.626; p = 0.015), ulcer size (OR 0.045, 95% CI 0.010–0.210; p < 0.0001), and a posterior ulcer location (OR 0.015, 95% CI 0.001–0.400; p = 0.012) were predictive factors for conversion to an open approach. Conclusion: This study confirms the benefits of the laparoscopic approach for the treatment of PPUs. Previous laparotomies, a greater ulcer size, and a posterior location of the ulcer are risk factors for conversion to open surgery during laparoscopic repair. [ABSTRACT FROM AUTHOR]

Background and Purpose: Waning immunity and the surge of SARS-CoV-2 variants are responsible for breakthrough infections, i.e., infections in fully vaccinated individuals. Although the majority of vaccinated infected subjects report mild or no symptoms, some others require hospitalization. The clinical and immunological features of vaccinated hospitalized COVID-19 patients are currently unknown. Methods: Twenty-nine unvaccinated and 36 vaccinated hospitalized COVID-19 patients were prospectively enrolled and clinical and laboratory data were gathered. Immunophenotyping of leukocytes' subsets, T and B cell SARS-CoV-2-specific responses were evaluated via flow cytometry. Anti-IFN-α autoantibodies were measured via ELISA. Results: Despite vaccinated patients were older and with more comorbidities, unvaccinated subjects showed higher levels of pro-inflammatory markers, more severe disease, and increased mortality rate. Accordingly, they presented significant alterations in the circulating leukocyte composition, typical of severe COVID-19. Vaccinated patients displayed higher levels of anti-Spike IgGs and Spike-specific B cells. Of all participants, survivors showed higher levels of anti-Spike IgGs and Spike-specific CD4+ T cells than non-survivors. At hospital admission, 6 out of 65 patients (9.2%) displayed high serum concentrations of autoantibodies targeting IFN-α. Remarkably, 3 were unvaccinated and eventually died, while the other 3 were vaccinated and survived. Conclusion: Despite more severe pre-existing clinical conditions, vaccinated patients have good outcome. A rapid activation of anti-SARS-CoV-2-specific immunity is fundamental for the resolution of the infection. Therefore, prior immunization through vaccination provides a significant contribution to prevention of disease worsening and can even overcome the presence of high-risk factors (i.e., older age, comorbidities, anti-IFN-α autoantibodies). [ABSTRACT FROM AUTHOR]

Purpose: SARS-CoV-2 infection in immunocompromised hosts is challenging, and prolonged viral shedding can be a common complication in these patients. We describe the clinical, immunological, and virological course of a patient with eosinophilic granulomatosis with polyangiitis, who developed the status of long-term asymptomatic SARS-CoV-2 carrier for more than 7 months. Methods: Over the study period, the patient underwent 20 RT-PCR tests for SARS-CoV-2 detection on nasopharyngeal swabs. In addition, viral cultures and genetic investigation of SARS-CoV-2 were performed. As for immunological assessment, serological and specific T-cell testing was provided at different time points. Results: Despite the patient showing a deep drug-induced B and T adaptive immunity impairment, he did not experience COVID-19 progression to severe complications, and the infection remained asymptomatic during the follow-up period, but he was not able to achieve viral clearance for more than 7 months. The infection was finally cleared by SARS-CoV-2-specific monoclonal antibody treatment, after that remdesivir and convalescent plasma failed in this scope. The genetic investigations evidenced that the infection was sustained by multiple viral subpopulations that had apparently evolved intra-host during the infection. Conclusion: Our case suggests that people with highly impaired B- and T-cell adaptive immunity can prevent COVID-19 progression to severe complications, but they may not be able to clear SARS-CoV-2 infection. Immunocompromised hosts with a long-term infection may play a role in the emergence of viral variants. [ABSTRACT FROM AUTHOR]

Background: Intra-abdominal abscesses (IAA) may develop after laparoscopic appendectomies (LA) for acute appendicitis. The identification of risk factors for postoperative IAA could lead to a decrease in the readmission rate and surgery redoes after LA for acute appendicitis. Materials and methods: The present study retrospectively analyzed patients undergone LA for acute appendicitis during the period 2001–2017. Clinical, intraoperative, and postoperative outcomes were described. Comparison between groups was made via univariate and multivariate analyses. Results: The charts of 2076 patients undergone LA were reviewed. Thirty-seven patients (1.8%) developed a postoperative IAA. Male gender (p < 0.05), ASA score ≥ 2 (p < 0.05), a gangrenous or perforated appendicitis (p < 0.0001), abscess or pelvic peritonitis (p < 0.0001), clipping the mesoappendix (p < 0.0001), appendix division by mechanical stapler (p < 0.05), prolonged antibiotic therapy (p < 0.05), and piperacillin/tazocin regimen (p < 0.0001) were significantly more frequent in the group of patients with IAA. In terms of multivariate analysis, only pelvic peritonitis (p = 0.010), perforated appendicitis (p = 0.0002), and clipping the mesoappendix (p = 0.0002) were independent predictive factors for postoperative IAA. Conclusion: Patients with peritonitis or a perforated appendicitis, and those who had their mesoappendix clipped showed a higher likelihood of developing an IAA. At risk patients should be provided with careful follow-up for the early detection and management of this complication. [ABSTRACT FROM AUTHOR]

Sphingosine 1-phosphate (S1P) has a role in many cellular processes. S1P is involved in cell growth and apoptosis, regulation of cell trafficking, production of cytokines and chemokines. The kinases SphK1 and SphK2 (SphKs) phosphorilate Sphingosine (Sph) to S1P and several phosphatases revert S1P to sphingosine, thus assuring a balanced pool that can be depleted by a Sphingosine lyase in hexadecenal compounds and aldehydes. There are evidences that SphK1 and 2 may per se control cellular processes. Here, we report that Sph kinases regulate IL-17 expression in human T cells. SphKs inhibition impairs the production of IL-17, while their overexpression up-regulates expression of the cytokine through acetylation of IL-17 promoter. SphKs were up-regulated also in PBMCs of patients affected by IL-17 related diseases. Thus, S1P/S1P kinases axis is a mechanism likely to promote IL-17 expression in human T cells, representing a possible therapeutic target in human inflammatory diseases. [ABSTRACT FROM AUTHOR]