Why Treat Patients with a Major Orthopaedic Surgery Only to Send Them Back to the Vulnerable Conditions That Made Them Sick in the First Place? A Conceptual Scenario to Improve Patient's Journey.

Individuals with severe cartilage degeneration of the hip or knee or collapsed vertebrae that cause spine deformities can suffer from joint and neuropathic pain in the back, disuse of the affected limb, and restriction of movements. Surgical intervention is the most widespread and successful solution to date. There is a general belief that eating healthy and staying physically and mentally active might have a preventive role against musculoskeletal disease occurrence, while instead, we are more certain of the benefits deriving from a healthy diet and exercise therapy after major orthopaedic procedures. These aspects are in fact vital components in enhanced recovery after surgery programmes. However, they are applied in hospital settings, are often centre-dependent, and lack primary and tertiary preventive efficacy since end once the patient is discharged. There is the lack of initiatives at the territorial level that ensure a continuum in the patient's journey towards orthopaedic surgery, home transition, and a healthy and long-lasting life. The expert panel advocates the integration of an intermediate lifestyle clinic that promotes healthy eating, physical activity, and sleep hygiene. In this facility directed by professionals in enhancing recovery after surgery, patients can be referred after the surgical indication and before home discharge. Surgery is in fact a moment when individuals are more curious to do their best to heal and stay healthy, representing a timepoint and opportunity for educating patients on how lifestyle changes may optimise not only their surgical recovery but also long-term future health state.

Perioperative adverse events in adult and pediatric spine surgery: A prospective cohort analysis of 364 consecutive patients.

Introduction: A precise knowledge of the possible Adverse Events (AEs) related to spinal surgical procedures is crucial in clinical practice. Research Question: Purposes of this study are: to determine the prevalence and severity of perioperative AEs associated with pediatric and adult spine surgery in a high volume center; to estimate the impact of perioperative AEs on length of hospital stay (LOS). Material and Methods: This is a prospective, observational, monocenter study, including 346 consecutive patients (294 adults and 52 pediatrics). The SAVES-V2 questionnaire was used to record AEs. The form was updated by the medical staff every time an adverse event was recorded during hospitalization. Results: 21,2% of pediatric patients and 20,7% of adults had at least 1 perioperative AEs. In adults, dural tear (3.1%) and neuropathic pain (4,8%), were the most frequent intraoperative and postoperative AE, respectively. In pediatric patients, neurologic deterioration was the most frequent postoperative AE. A diagnosis of deformity (p=0.01), an ASA grade equal or superior to 3 (p=0.023) and the procedure 'Posterior Spinal Fusion' (p=0.001) were associated with a higher frequency of AEs. AEs required prolonged LOS in 40 cases, 7 (70%) pediatric patients and 33 (65%) adults. Discussion and Conclusion: The overall prevalence of AEs is 20.8%, and, although the distribution is almost equal between adult and pediatric patients, their severity is related to age, being higher in pediatric patients. Deformities, deformity correction, revision surgery and AP surgery are the most impactful factors. AEs seriously affect hospitalization, with prolonged LOS (mean 6 days).

Sero-survey on long-term care facility residents reveals increased risk of sub-optimal antibody response to BNT162b2: implications for breakthrough prevention.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on residents of long-term care facilities (LTCFs) has been dramatic on global scale as older age and comorbidities pose an increased risk of severe disease and death. METHODS: Aim of this study was to evaluate SARS-CoV-2 Spike-specific IgG (S-IgG) antibody titers in 478 residents and 649 health care workers of a large Italian long-term care facility two months after complete vaccination with BNT162b2. Associations among resident-related factors and predictors of humoral response were investigated. RESULTS: By stratifying levels of humoral responses, we found that 62.1%, 21.6%, 12.1% and 4.2% of residents had high (>1,000 BAU/ml), medium (101-1,000), low (1-100) and null (<1 BAU/mL) S-IgG titers, respectively. Residents with documented previous COVID-19 and those with SARS-CoV-2 nucleocapsid-specific IgG (N-IgG) positive serology showed higher level of serological response, while significant associations were observed for cancer with suboptimal response (p = 0.005) and the administration of corticosteroid for suboptimal response (p = 0.028) and a null one (p = 0.039). According to multivariate logistic regression, predictors of an increased risk of null response were advanced age (Odd ratio, OR: 2.630; Confidence interval, CI: 1.13-6.14; p = 0.025), corticosteroid therapy (OR: 4.964; CI: 1.06-23.52; p = 0.042) and diabetes mellitus (OR:3.415; CI:1.08-10.8; p = 0.037). In contrast, previous diagnosis of COVID-19 was strongly associated with a reduced risk of null response to vaccination (OR:0.126; CI:0.02-0.23; p < 0.001). CONCLUSIONS: SARS-CoV-2 specific antibodies in elderly individuals should be consider when deciding the need of a third dose of vaccine for prevention of reinfections in LTCFs despite the maintenance of barrier measures.

Mast Cell Cytokines IL-1, IL-33, and IL-36 Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-Inflammatory Cytokines IL-37, IL-38, and IL-1Ra.

Psoriasis (PS) is a skin disease with autoimmune features mediated by immune cells, which typically presents inflammatory erythematous plaques, and is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells, including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature, and reside in vascularized tissues. They can be activated by antigen-provoking overexpression of proinflammatory cytokines, and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophages to release IL-36-a powerful proinflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic proinflammatory diseases such as psoriasis. Suppression of IL-36 could result in a dramatic improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra, which binds to IL-36 receptor ligands, but suppression can also occur by binding IL-38 to the IL-36 receptor (IL-36R). IL-38 specifically binds only to IL-36R, and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs-a process that activates macrophages to secrete proinflammatory IL-36 inhibited by IL-38. IL-37 belongs to the IL-1 family, and broadly suppresses innate inflammation via IL-1 inhibition. IL-37, in murine models of inflammatory arthritis, causes the suppression of joint inflammation through the inhibition of IL-1. Therefore, it is pertinent to think that IL-37 can play an inhibitory role in inflammatory psoriasis. In this article, we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis, and hold promise as an innovative therapeutic tool.

Changes of clinical activities in an orthopaedic institute in North Italy during the spread of COVID-19 pandemic: a seven-week observational analysis.

PURPOSE: The COVID-19 pandemic is importantly affecting the orthopaedic practice all over the world with Northern Italy being the first European area that faced the worst scenario. In this study, the changes in clinical practice occurred in an orthopaedic center in Milan are described. METHODS: Number and type of admissions, outpatients cancelled and preserved, emergency room, and intensive care unit activities have been analyzed in the timeframe of seven weeks since the beginning of the pandemic (from February 24th to April 10th) and compared with the same period in 2019. RESULTS: The planned surgical admissions declined from 2172 in 2019 to 664 in 2020 (69.42%, p < 0.0001), while emergencies increased from 158 to 268 (69.62%). The rehabilitation admissions declined from 414 to 69 (83.33%). The overall admission decreased by 63.52%, the trend showed a drop in the last weeks. Surgery performed in the COVID-19 operating room increased by 16.7% in the last week. Seven deaths occurred (0.7% of all orthopaedics and trauma admissions) compared with four (0.1%) which happened in the same period in 2019 (p = 0.004). Six of these patients were suffering from COVID-19. A total of 23,580 outpatients (93.8%) were cancelled. Emergency room consultations declined by 68.14% and 63.47% among white and green priority, respectively, while increased by 25% and 100% among yellow and red, respectively. CONCLUSION: These numbers show the radical changed scenario in an orthopaedic center in Milan during COVID-19 pandemic. Elective surgery declined rapidly going close to zero, outpatient admissions were restricted to cases that cannot be postponed, while emergencies increased due to the role played by the hospital as referral orthopaedic centre during the pandemic. The still ongoing emergency will have important impacts on the overall orthopaedic healthcare management for the next months.

Does specialty matter? A survey on 176 Italian neurosurgeons and orthopedic spine surgeons confirms similar competency for common spinal conditions and supports multidisciplinary teams in comprehensive and complex spinal care.

BACKGROUND CONTEXT: Spine surgery is a multifaceted subspeciality requiring a breadth of knowledge and skill from different branches of medicine for the treatment of pathologies varying from degenerative to deformity, oncological, and trauma. PURPOSE: The aim of the study was to investigate the self-perceived competency of spine surgeons in relation to different types of spinal procedures. STUDY DESIGN/SETTING: This is a survey study. METHODS: We conducted a survey on 176 surgeons (orthopedic surgeons and neurosurgeons). The instrument used for the assessment of the perceived ability was a survey consisting of 21 items (scenarios) developed and distributed through a professional online survey service to ensure confidentiality and anonymity. A newly proposed procedure-specific rating survey was used for the evaluation. Kruskal-Wallis non-parametric test was used to assess validity. A p-value of <.05 was considered statistically significant. A Cronbach α value of >0.8 indicated reliability. RESULTS: Between the respondents (101), 47.5% were orthopedic surgeons and 52.5% were neurosurgeons. The internal consistency of the questionnaire was satisfactory (Cronbach α=0.93). For common spinal conditions, the orthopedic surgeons and the neurosurgeons perceived a similar competency. The neurosurgeons felt more competent in some cervical conditions (upper cervical procedures, myelopathy) and in neurologic tumors of the spine. The orthopedic surgeons felt more competent in deformities of the spine and in pelvic trauma. CONCLUSIONS: Self-perceived surgical competency for common spinal conditions is similar for orthopedic and neurosurgically trained spine surgeons. For less common conditions and clinical scenarios, the combination of both specialties seems to cover better the full spectrum of surgical care for spinal conditions. Multidisciplinary teams and comprehensive, multidisciplinary spinal surgical training should be considered to provide full coverage of spinal pathology.

Immunogenicity and safety of seasonal influenza vaccination in patients with classic Kaposi's sarcoma.

Classic Kaposi's sarcoma (cKS) is a human herpesvirus-8 (HHV-8)-associated lympho-angioproliferative tumor typically occurring in the elderly. It is associated with HHV-8-driven perturbed balance of peripheral B-cell subsets, which may have an impact on immune responses to antigenic stimulation. We took advantage of the common practice of cKS patients to undergo seasonal influenza vaccination because of advanced age and analyzed the immunogenicity and safety of licensed trivalent influenza vaccine in 46 cKS patients and 44 matched controls. Licensure criteria for immunogenicity were fulfilled in both groups. Four weeks after vaccination, hemagglutination-inhibition antibody titers against each viral strain contained in the vaccine increased in patients and controls (all P<0.001). Protection against at least one strain was achieved by 96% of cKS and 91% of control subjects. Protection against all strains persisted after 12 weeks, demonstrating a long-lasting response to vaccination. The vaccine was equally well tolerated by patients and controls, as assessed by evaluating solicited local and systemic reactions to the vaccine, and appearance or increase of antinuclear autoantibodies. HHV-8 virological rebound was observed in four cKS patients, but was not accompanied by progression of KS lesions. We conclude that seasonal influenza vaccine given to cKS patients is immunogenic and safe.

Long-term patterns of humoral and cellular response after vaccination against influenza A (H1N1) in patients with hematologic malignancies.

OBJECTIVES: The efficacy of a novel vaccine against influenza virus A (H1N1) in patients with hematologic malignancies is largely unknown. METHODS: We prospectively evaluated the humoral and cellular immune responses after one injection of monovalent adjuvanted 2009 H1N1 vaccine in 47 adults with hematologic malignancies and 77 controls by hemagglutination-inhibition assay and flow-cytometry analysis on day 0, 28, 50, and 90. RESULTS: On day 28 postvaccination, patients had lower seroprotection (95.2% vs. 75.2%, P < 0.01) and seroconversion (88.7% vs. 51.1%, P < 0.01) rates, as well as geometric mean titer (GMT; 256 vs. 134, P < 0.05), relative to controls. Response to vaccination varied according to the evaluated time point and the patient status: Patients not receiving chemotherapy had seroprotection and GMTs similar to controls in all time points, while patients receiving chemotherapy or allogeneic hematopoietic stem cell transplant (HSCT) had lower seroprotection and seroconversion levels than controls on day 28 and 50. EMEA cutoffs for efficacy were reached from day 28 by patients in follow-up or under treatment and only from day 90 by those with HSCT, especially if still under immunosuppressants. Patients treated with immunomodulatory drugs had higher antibody responses in terms of seroprotection and GMTs. T- and NK cell-mediated responses mounted from day 50 and did not differ between patients and controls. CONCLUSIONS: According to EMEA recommendation, H1N1 vaccination strategy was effective at protecting most of the hematologic patients, but needed to be improved in those more immunocompromised.

Human herpesvirus-8 infection leads to expansion of the preimmune/natural effector B cell compartment.

BACKGROUND: Human herpesvirus-8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS) and of some lymphoproliferative disorders of B cells. Most malignancies develop after long-lasting viral dormancy, and a preventing role for both humoral and cellular immune control is suggested by the high frequency of these pathologies in immunosuppressed patients. B cells, macrophages and dendritic cells of peripheral lymphoid organs and blood represent the major reservoir of HHV-8. Due to the dual role of B cells in HHV-8 infection, both as virus reservoir and as agents of humoral immune control, we analyzed the subset distribution and the functional state of peripheral blood B cells in HHV-8-infected individuals with and without cKS. METHODOLOGY/PRINCIPAL FINDINGS: Circulating B cells and their subsets were analyzed by 6-color flow cytometry in the following groups: 1- patients HHV-8 positive with classic KS (cKS) (n = 47); 2- subjects HHV-8 positive and cKS negative (HSP) (n = 10); 3- healthy controls, HHV-8 negative and cKS negative (HC) (n = 43). The number of B cells belonging to the preimmune/natural effector compartment, including transitional, pre-naïve, naïve and MZ-like subsets, was significantly higher among HHV-8 positive subjects, with or without cKS, while was comparable to healthy controls in the antigen-experienced T-cell dependent compartment. The increased number of preimmune/natural effector B cells was associated with increased resistance to spontaneous apoptosis, while it did not correlate with HHV-8 viral load. CONCLUSIONS/SIGNIFICANCE: Our results indicate that long-lasting HHV-8 infection promotes an imbalance in peripheral B cell subsets, perturbing the equilibrium between earlier and later steps of maturation and activation processes. This observation may broaden our understanding of the complex interplay between viral and immune factors leading HHV-8-infected individuals to develop HHV-8-associated malignancies.