Mathew, Amal

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant demyelinating neuropathy characterized by an increased susceptibility to peripheral nerve injury from trauma, compression, or shear forces. Patients with this condition are unique, necessitating distinct considerations for anesthesia and surgical teams. This review describes the etiology, prevalence, clinical presentation, and management of HNPP and presents contemporary evidence and recommendations for optimal care for HNPP patients in the perioperative period. While the incidence of HNPP is reported at 7–16:100,000, this figure may be an underestimation due to underdiagnosis, further complicating medicolegal issues. With the subtle nature of symptoms associated with HNPP, patients with this condition may remain unrecognized during the perioperative period, posing significant risks. Several aspects of caring for this population, including anesthetic choices, intraoperative positioning, and monitoring strategy, may deviate from standard practices. As such, a tailored approach to caring for this unique population, coupled with meticulous preoperative planning, is crucial and requires a multidisciplinary approach.

This research analyzes immunological response patterns to SARS-CoV-2 infection in blood and urine in individuals with serum cotinine-confirmed exposure to nicotine. Samples of blood and urine were obtained from a total of 80 patients admitted to hospital within 24 h of admission (tadm), 48 h later (t48h), and 7 days later (t7d) if patients remained hospitalized or at discharge. Serum cotinine above 3.75 ng/mL was deemed as biologically significant exposure to nicotine. Viral load was measured with serum SARS-CoV-2 S-spike protein. Titer of IgG, IgA, and IgM against S- and N-protein assessed specific antiviral responses. Cellular destruction was measured by high mobility group box protein-1 (HMGB-1) serum levels and heat shock protein 60 (Hsp-60). Serum interleukin 6 (IL-6), and ferritin gauged non-specific inflammation. The immunological profile was assessed with O-link. Serum titers of IgA were lower at tadm in smokers vs. nonsmokers (p = 0.0397). IgM at t48h was lower in cotinine-positive individuals (p = 0.0188). IgG did not differ between cotinine-positive and negative individuals. HMGB-1 at admission was elevated in cotinine positive individuals. Patients with positive cotinine did not exhibit increased markers of non-specific inflammation and tissue destruction. The blood immunological profile had distinctive differences at admission (MIC A/B↓), 48 h (CCL19↓, MCP-3↓, CD28↑, CD8↓, IFNγ↓, IL-12↓, GZNB↓, MIC A/B↓) or 7 days (CD28↓) in the cotinine-positive group. The urine immunological profile showed a profile with minimal overlap with blood as the following markers being affected at tadm (CCL20↑, CXCL5↑, CD8↑, IL-12↑, MIC A/B↑, GZNH↑, TNFRS14↑), t48h (CCL20↓, TRAIL↓) and t7d (EGF↑, ADA↑) in patients with a cotinine-positive test. Here, we showed a distinctive immunological profile in hospitalized COVID-19 patients with confirmed exposure to nicotine.

The release of danger signals from tissues in response to trauma during cardiac surgery creates conditions to reprogram the immune system to subsequent challenges posed by pathogens in the postoperative period. To demonstrate this, we tested immunoreactivity before surgery as the baseline (tbaseline), followed by subsequent challenges during the acute phase (t24h), convalescence (t7d), and long-term recovery (t3m). For 108 patients undergoing elective heart surgery, whole blood was stimulated with lipopolysaccharide (LPS), Influenza A virus subtype N2 (H3N2), or the Flublok™ vaccine to represent common pathogenic challenges. Leukocytosis, platelet count, and serum C-reactive protein (CRP) were used to measure non-specific inflammation. Cytokines were measured after 18 h of stimulation to reflect activation of the various cell types (activated neutrophils–IL-8; activated T cells-IL-2, IFNγ, activated monocyte (MO)-TNFα, IL-6, and deactivated or atypically activated MO and/or T cells–M-CSF, IL-10). IL-2 and IL-10 were increased at t7d, while TNFα was suppressed at t24h when LPS was utilized. Interestingly, M-CSF and IL-6 production was elevated at seven days in response to all stimuli compared to baseline. While some non-specific markers of inflammation (white cell count, IL-6, and IL-8) returned to presurgical levels at t3m, CRP and platelet counts remained elevated. We showed that surgical stimulus reprograms leukocyte response to LPS with only partial restoration of non-specific markers of inflammation.