Is It Time to Create Training Pathways Allowing Earlier Subspecialization within the "House of Orthopaedics"?: AOA Critical Issues.

ABSTRACT: The ability to train an orthopaedic resident in all aspects of orthopaedics in 5 years has become increasingly difficult due to the growth in knowledge and techniques, work-hour restrictions, and reduced resident autonomy. It has become nearly universal for our residents to complete at least 1 subspecialty fellowship prior to entering practice. In some subspecialties, the skills necessary to practice competently have become difficult to master. Simply adding to the current length of training may not address these issues effectively and would add to the economic cost of residency training. Novel training pathways that allow residents to focus earlier and in greater depth on their intended subspecialty while maintaining general orthopaedic competencies can be created without lengthening training. It is time to initiate discussions about these possibilities.

Post-operative morbidity in Crohn's disease: what is the impact of patient-, disease- and surgery-related factors?

PURPOSE: Over 50% of patients suffering from Crohn's disease (CD) require surgery in their lifetime. Predictors/risk factors of post-operative morbidity and mortality in CD are poorly investigated. We aimed to assess the risk factors of post-operative morbidity/mortality in CD. METHODS: We performed a retrospective cohort study in which all CD patients operated and followed up at our tertiary Inflammatory Bowel Disease Centre from 2014 to 2019 were enrolled. For each patient, we evaluated patient-dependent, disease-dependent and surgery-dependent variables. All patients underwent small bowel and/or colic resections. RESULTS: Of the 165 operated patients, forty-two (25.5%) developed post-operative complications (major complication rate = 9.8%) including wound infection (12.1%), respiratory complications (4.8%), prolonged ileum (4.2%), anastomotic leak (3.6%), urinary infections (3%), abdominal abscess (2.4%), anastomotic bleeding (3.6%), abdominal bleeding (1.2%) and obstruction (0.6%). Two subjects (1.2%) required re-operation within 30 days, and one died. A surgery duration < 141 min was predictive of a better post-operative outcome (sensitivity 80.9%, specificity 43.1%, PPV 32.7%, NPV 86.9%). The multivariable analysis showed stricturing/fistulizing behaviour (OR 3.7, 95% CI 1.6-6.4, p = 0.02), need for total parenteral nutrition (OR 4.1, 95% CI 2.4-9.2, p = 0.01), pre-operative bowel cleansing (OR 0.6, 95% CI 0.41-0.83, p = 0.01) and surgery duration < 141 min (OR 0.2, 95% CI 0.08-0.7, p = 0.03) as the only risk factors associated with post-operative morbidities. CONCLUSIONS: About 25% of CD patients develop post-operative complications. Several patient-related, disease-related and surgery-related factors should be considered risk factors for post-operative morbidity. The recognition of these factors, as well as a multidisciplinary approach to the pre-operative management of CD, could reduce post-operative complications.

Operative costs associated with arthroscopic assisted open reduction and internal fixation of acute ankle fractures.

BACKGROUND: Ankle fractures are a common orthopedic injury that frequently involves associated cartilage lesions, soft tissue damage, and a significant inflammatory burden. Despite studies revealing intra-articular pathology in up to 79% of ankle fractures, only 1% of open reduction and internal fixation (ORIF) procedures undergo arthroscopic evaluation. The primary purpose of this study was to determine the cost effectiveness of ankle arthroscopy performed at time of ORIF for ankle fracture. METHODS: An IRB approved retrospective review of patients who sustained ankle fractures and underwent ORIF with and without concomitant arthroscopic surgery between 2015 and 2020 were investigated. Patient demographics, fracture characteristics, outcomes, and cost data were collected and analyzed. RESULTS: There were 567 total ORIF and 28 ORIF and scope included for cost analysis purposes. Total surgical costs averaged $6,537.62 and $6,886.46 for the ORIF only and ORIF and scope procedures respectively. Total direct costs, including operating room time, for the same procedures were found to average $6,212.34 and $7,312.10 for the ORIF only and ORIF and scope procedures respectively. The cost difference between the ORIF only and with arthroscopy was not statistically significant (p = 0.1174). Twelve of the 28 arthroscopic patients (42.86%) had grade 3 or full thickness chondral lesions, and 11/28 (39.28%) arthroscopic patients were found to have grade 1-2 cartilage changes. CONCLUSION: In the acute treatment of ankle fractures, concurrent arthroscopic evaluation does not add a significant cost to the procedure and may result in improved short and long term benefits for the patient. With improved arthroscopic efficiency, the cost differential can be further reduced. LOE: IV.

SARS-CoV-2 infection does not induce HIV viral escape in the central nervous system: A case series.

We report two cases of HIV positive patients with SARS-CoV-2 infection and a recent diagnosis of opportunistic infections of central nervous system (CNS). We investigated the potential impact of coinfection with SARS-CoV-2 on HIV replication in CNS.

Laboratory-based surveillance of invasive listeriosis in Northern Italy over a fourteen-year period: epidemiological and clinical results.

INTRODUCTION: Invasive listeriosis is a rare foodborne disease with a significant impact on public health worldwide, because of the severity of its clinical manifestations and high fatality rate. In this study, we provide a snapshot of epidemiology of listeriosis in Lombardy Region, Northern Italy, reviewing enhanced surveillance data collected over fourteen years, after the implementation of a voluntary laboratory-based surveillance system for the referral of clinical isolates of Listeria monocytogenes to a regional reference laboratory, since 2005. METHODS: Invasive listeriosis cases data from 2005 to 2018 were extracted from the regional laboratory-based surveillance system database and compared with the regional mandatory notification disease system data. RESULTS: Over the fourteen-year period under study, 533 Listeria monocytogenes isolates were detected by the laboratory surveillance system, 55 of which from pregnancy-related cases. The median age of non-pregnancy-associated patients was 71 years, with 64.6% of cases observed in the elderly. Cases with underlying medical risk conditions accounted for 92.1%, and the fatality rate was 26.2%. By integrating data from the mandatory notification system and the laboratory-based surveillance system, a total of 935 cases were recorded. The collection of data through the laboratory surveillance system allowed to increase the surveillance sensitivity by 18%. CONCLUSIONS: Our results documented the growing epidemiological relevance of listeriosis through the analysis of two information sources, the regional mandatory notification system and the regional laboratory-based surveillance system. The data we obtained were consistent with the literature, except for pregnancy-related cases, which are often underdiagnosed. This study highlighted the importance of laboratory-based surveillance system, which led to a significant increase in the sensitivity of the mandatory notification system.

Genetic variability of the measles virus hemagglutinin gene in B3 genotype strains circulating in Northern Italy.

Sequencing the whole measles virus hemagglutinin (H) gene, in conjunction with a 450-nucleotide region of the nucleoprotein gene (N-450), is helpful for the identification of new genotypes and as an auxiliary in outbreak characterization. In addition, it is essential to be able to predict the antigenic changes of the H protein to gain a better monitoring of the response to the vaccine. In this study, we obtained the full-length H gene sequences from 19 measles virus (MV) strains belonging to two B3 genotype variants circulating in Lombardy (Northern Italy) between July 2015 and February 2016 and evaluated the variability of the whole MV-H gene. Furthermore, we compared the obtained H amino acid sequences to all MV sequences available in the GenBank database (n = 1152 in total) and analyzed the amino acid substitutions in the H protein within clades where the Italian strains were included. We identified a higher variability in the H gene compared to the N-450 region and our results support previous studies, highlighting that the H gene is more informative for characterizing the MV B3 genotype than the N-450 sequence. Some of the amino acid substitutions were fixed in the viral population and, remarkably, some of the amino acid substitutions were typically present only in the Italian sequences. Accumulating further molecular information about MV-H gene will be necessary to enable in-depth analyses of the variability of this gene in the vaccinated population.

Correlation of pre-operative planning to surgical correction of opening wedge HTO: a radiographic study utilizing a manual measurement method.

High tibial osteotomy (HTO) utilizing a medial opening wedge has become a common and effective surgical technique for treatment of isolated medial compartment knee osteoarthritis secondary to varus malalignment. To reduce the risk of under- or overcorrection, accurate preoperative planning is important. This is a radiographic study to evaluate the reliability of preoperative measurement on full-length weight-bearing X-rays (FLWBXr) compared to post-operative X-rays after healing. In addition, we calculated if the intraoperative opening wedge performed was consistent with the preoperative calculation and the postoperative correction. Three independent observers measured preoperative and postoperative FLWBXr at three different times. The angle of varus deformity; the angle to correct and the wedge needed to achieve desired alignment: the angle achieved postoperatively, and the postoperative mechanical axis deviation were measured. Intra- and inter-rater reliability showed high values for all the investigated parameters. The discrepancy between the calculated wedge and the wedge actually used in surgery ranged from 1 mm of over-correction to 3 mm of undercorrection, averaging -1.3 mm. The mechanical axis crossed the tibial plateau an average of 53% ±12.7. Clustering the data by the plate type statistically significant differences were found for preoperative varus alignment, advocated correction, intraoperative correction and post-op alignment. The Dugdale method can be considered highly reliable. Possible factors affecting the final correction are: surgeon's desire not to overcorrect in young patients and minimal osteoarthritis; measurement errors; variability in the method the FLWBXr is performed. In addition, the under correction could be the result of some collapse with time or the correction could be affected by the fixation system. Further investigation should include complete post-operative evaluation of outcomes and assess the role of these potential factors and their relationship to correction. Level of Evidence: Level III, Retrospective study.

Talar exostosis (epiphyseal dysplasia): case report of posterior arthroscopic excision.

Posterior ankle impingement is a syndrome characterized by discomfort or pain at the hind foot during plantarflexion. The etiology can be divided into three main categories: overuse, trauma and anatomic abnormalities. Regarding overuse, usually patients that complain of posterior ankle pain are ballet dancers, downhill runners, field athletes and soccer players secondary to flexor hallucis tendinitis.

Genetic characterisation of Measles virus variants identified during a large epidemic in Milan, Italy, March-December 2017.

In 2017, Italy experienced a large measles epidemic with 5408 cases and four deaths. As Subnational Reference Laboratory of the Measles and Rubella surveillance NETwork (MoRoNET), the EpiSoMI (Epidemiology and Molecular Surveillance of Infections) Laboratory (University of Milan) set up rapid and active surveillance for the complete characterisation of the Measles virus (Mv) responsible for the large measles outbreak in Milan and surrounding areas (Lombardy, Northern Italy). The aims of this study were to describe the genetic profile of circulating viruses and to track the pathway of measles transmission. Molecular analysis was performed by sequencing the highly variable 450 nucleotides region of the N gene (N-450) of Mv genome. Two-hundred and ninety-nine strains of Mv were analysed. The phylogenetic analysis showed five different variants, two not previously described in the studied area, belonging to D8 and B3 genotypes. Three events of continuous transmission of autochthonous variants (D8-Osaka, D8-London and B3-Milan variants) and two events of continuous transmission of imported variants (B3-Dublin and D8-Hulu Langat) tracked five different transmission pathways. These pathways outlined two epidemic peaks: the first in April and the second in July 2017. The correlation between Mv variant and the epidemiological data may enable us to identify the sources of virus importation and recognise long-lasting virus transmission pathways.

Measles surveillance activities in the Metropolitan Area of Milan during 2017-2018.

INTRODUCTION: In Italy, the transmission of measles is still endemic, and 7,919 cases were reported to the National Surveillance System between January 2017 and December 2018. Aim of this study is to report the results of the measles surveillance activities in the Metropolitan City of Milan from March 2017 to December 2018, and to evaluate the surveillance performance WHO indicators. METHODS: The Local Health Units (LHUs) carried out case investigations and collected specimens to send to the EpiSoMI Lab (Subnational Reference Laboratory, SRL) of the University of Milan for cases/outbreaks confirmation and genotyping performed according to the WHO Guidelines. RESULTS: Overall, 610 suspected measles cases were reported by the surveillance system of the Metropolitan City of Milan. A total of 439 out of 540 cases with adequate specimens were laboratory-confirmed by molecular and/or serological assays. Two-hundred and thirty-six cases were notified as sporadic and 203 as related to 94 outbreaks. The most confirmed cases were aged 15-39 years, almost all not vaccinated. Overall, 282 cases were genotype D8 and 118 genotype B3.The evaluation of a set of indicators to monitor the quality of surveillance activities demonstrated the proficiency of the EpiSoMI Lab. CONCLUSIONS: A well-done investigation of cases and outbreaks by the surveillance local system, in a timely manner, in order to notify and investigate suspected cases and to laboratory confirm or discard cases is fundamental to reduce morbidity, to prevent further virus transmission and to achieve measles elimination.

Cervical Human Papillomavirus genotypes in HIV-infected women: a cross-sectional analysis of the VALHIDATE study.

INTRODUCTION: Primary-prevention by prophylactic vaccination against HPV-related cancers and HPV-based screening programs are based on HPV-type distribution in immunocompetent individuals. HIV-infected women are at high risk of invasive HPV-disease sustained by a broader range of HPV-types and have higher multi-type infection rates than immunocompetent hosts. METHODS: This is a cross-sectional analysis of High Risk HPV (HR HPV) type distribution in 805 HIV+ women (HIW) compared with a control group of 1402 immunocompetent HIV- women (SPW) enrolled in the VALHIDATE study in order to define HPV type-specific distribution according to cytology. RESULTS: HIW had a 3.8, 3.6, and 2.7 times higher risk of atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL) than SPW respectively. HPV-DNA prevalence was 28.4% in HIW and 11.81% in SPW (p<0.0001). The prevalence of infection increased from normal cytology to HSIL both in HIW (from 21.45% to 90.91%) and SPW (from 9.54% to 75%). The OR for women with normal cytology of having a positive HPV-DNA test result of was 2.6 times higher in HIW than in SPW. The cumulative prevalence of HPV-16/18 in HSIL is much lower in HIW (36.4±28.4) than SPW (62.5±33.5). CONCLUSIONS: A higher prevalence of infection and broader HPV type distribution were observed in HIV+ women compared to the general population. More than 60% of HSIL lesions of HIW patients are caused by single or multi-type infections from non-HPV16/18 HPVs. The potential 9v-HPV vaccine coverage could be even higher than that expected for the general population given the wide panel of HPV-types observed in the HSIL of HIV+ women.

Molecular epidemiology and genotyping of Chlamydia trachomatis infection in a cohort of young asymptomatic sexually active women (18-25 years) in Milan, Italy.

INTRODUCTION: Chlamydia trachomatis (Ct) is the most common bacterial cause of sexually transmitted infections (STI) and is associated with severe long-term sequelae in female populations. In Italy Ct infections are not submitted to a screening programme, and its epidemiological profile is understudied. Even scarcer information is available about the genetic diversity on ompA gene, whose sequence defines 18 different genovars. This study aims at evaluating the prevalence of Ct infection in young sexually active asymptomatic women aged 18-25, and characterizing the molecular epidemiology of the different circulating genovars in this population. METHODS: Cervical samples collected from 909 sexually-activeyoung women (mean age 21.5 years) were analyzed through molecular assay for the detection of Ct infection. Phylogenetic analysis on the ompA gene was performed on Ct positive samples to identify the circulating genovars. RESULTS: The overall prevalence of Ct-infection was 4.4% (95%CI: 3.2-5.9%): 5.3% among women aged 18-21 years and 3.5% among those aged 22-25 years. Phylogenetic analysis has identified 5 different genovars: D, E, F, G, and H. The most common genovar was the E (46%), followed by genovar F and G (18.9% each), D (13.5%), and H (2.7%). CONCLUSIONS: This study underlines the high prevalence of asymptomatic Ct-infections among young women. Overall, about half of the asymptomatic infections is sustained by genovar E. The introduction in Italy of a systematic screening program should be considered to allow a better understanding of Ct spreading and providing women with an opportunity for early treatment to protect their sexual and reproductive health.

HPV genotypes detected in the oropharyngeal mucosa of HIV-infected men who have sex with men in Northern Italy.

The aim of this study was to investigate the epidemiological profile of HPV oropharyngeal infections in HIV-infected men who have sex with men. A total of 135 subjects were enrolled at the L. Sacco University Hospital (Milan, Italy) to evaluate their HPV oropharyngeal infection status at baseline and at a follow-up visit at least 12 months later. HPV DNA was detected from oropharyngeal swabs using an in-house nested PCR that amplifies a segment of the L1 gene. The PCR products were then sequenced and genotyped. A greater percentage of high-risk genotypes was identified compared to low-risk genotypes (13·7% vs. 6·9%, P < 0·05), and two uncommon alpha-HPV genotypes were detected, i.e. HPV-102 and HPV-114. HPV infection prevalence was 24·4% and the cumulative incidence was 24·1%. During the follow-up period, one case of HPV infection (HPV-33) persisted, while the overall rate of infection clearance was 58·3%. HPV oropharyngeal infection was widespread in the cohort examined, and most of the infections were transient and cleared within 12 months. These results may help to clarify the role of HPV in the oropharynx and may also improve our understanding of the need to implement preventive strategies in at-risk populations.

KOOS pain as a marker for significant knee pain two and six years after primary ACL reconstruction: a Multicenter Orthopaedic Outcomes Network (MOON) prospective longitudinal cohort study.

OBJECTIVE: The prevalence of radiographic osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR) approaches 50%, yet the prevalence of significant knee pain is unknown. We applied three different models of Knee injury and Osteoarthritis Outcome Score (KOOS) thresholds for significant knee pain to an ACLR cohort to identify prevalence and risk factors. DESIGN: Multicenter Orthopaedic Outcomes Network (MOON) prospective cohort patients with a unilateral primary ACLR and normal contralateral knee were assessed at 2 and 6 years. Independent variables included patient demographics, validated Patient Reported Outcomes (PRO; Marx activity score, KOOS), and surgical characteristics. Models included: (1) KOOS criteria for a painful knee = quality of life subscale <87.5 and ≥2 of: KOOSpain <86.1, KOOSsymptoms <85.7, KOOSADL <86.8, or KOOSsports/rec <85.0; (2) KOOSpain subscale score ≤72 (≥2 standard deviations below population mean); (3) 10-point KOOSpain drop from 2 to 6 years. Proportional odds models (alpha ≤ 0.05) were used. RESULTS: 1761 patients of median age 23 years, median body mass index (BMI) 24.8 kg/m(2) and 56% male met inclusion, with 87% (1530/1761) and 86% (1506/1761) follow-up at 2 and 6 years, respectively. At 6 years, n = 592 (39%), n = 131 (9%) and n = 169 (12%) met criteria for models #1 through #3, respectively. The most consistent and strongest independent risk factor at both time-points was subsequent ipsilateral knee surgery. Low 2-year Marx activity score increased the odds of a painful knee at 6 years. CONCLUSIONS: Significant knee pain is prevalent after ACLR; with those who undergo subsequent ipsilateral surgery at greatest risk. The relationship between pain and structural OA warrants further study.

Bone marrow CD34+ progenitor cells may harbour HIV-DNA even in successfully treated patients.

The issue about bone marrow hematopoietic progenitor cells harbouring HIV-DNA in infected patients is still under scrutiny. We studied nine HIV-infected individuals undergoing bone marrow aspiration for diagnostic purposes. In all patients, even in those receiving successful antiretroviral therapy for several years, HIV-DNA was detected in purified CD34+ lineage-bone marrow progenitor cells. This finding, although not conclusive due to the low number of patients examined, adds further evidence that current treatment strategies may be insufficient to resolve latent infection in bone marrow CD34+ hematopoietic progenitor cells.

Safety and efficacy of turoctocog alfa (NovoEight®) during surgery in patients with haemophilia A: results from the multinational guardian™ clinical trials.

Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prevention and treatment of bleeding episodes in patients with haemophilia A. The present investigations from the multinational, open-label guardian(™) clinical trials assessed the haemostatic response of turoctocog alfa (NovoEight(®)), a rFVIII product, in patients with severe haemophilia A (FVIII ≤ 1%) undergoing surgery. All patients had a minimum of 50 exposure days to any FVIII product prior to surgery and no history of inhibitors. A total of 41 procedures (13 orthopaedic, 19 dental and 9 general) were performed in 33 patients aged 4-59 years. Of the 41 procedures, 15 were major surgeries in 13 patients and 26 were minor surgeries in 21 patients. The success rate for haemostatic response was 100% (success was defined as 'excellent' or 'good' haemostatic outcome). Turoctocog alfa consumption on the day of surgery ranged from 27 to 153 IU kg(-1). The mean daily dose declined over time, while retaining adequate FVIII coverage as measured by trough levels. Overall, no safety issues were identified. No thrombotic events were observed and none of the patients developed FVIII inhibitors. In conclusion, the present results show that turoctocog alfa was effective in controlling blood loss by obtaining a sufficient haemostatic response in patients with severe haemophilia A undergoing surgery.

A novel multiplex one-step real-time RT-PCR assay for the simultaneous identification of enterovirus and parechovirus in clinical fecal samples.

INTRODUCTION: Enterovirus (EV) and parechovirus (PeV) can either infect humans asymptomatically or can cause gastroenteritis, respiratory symptoms and, sometimes, severe disease. As the number of newly identified EV and PeV genotypes keeps increasing, diagnostic methods need to be updated. To this end, we described a novel multiplex one-step real-time RT-PCR to detect EV and human PeV (HPeV) simultaneously in fecal samples collected from children with rotavirus group A (RV-A)-related gastroenteritis. METHODS: The specificity and sensitivity of the EV/HPeV realtime RT-PCR were evaluated with two 2011 Quality Control for Molecular Diagnostics (QCMD) panels for EV and HPeV detection. RNA was extracted from 111 RV-A-positive fecal samples collected from children up to 5 years of age who had been hospitalized for gastroenteritis from September 2010 to August 2011. RESULTS: The EV/HPeV real-time RT-PCR showed a 100% sensitivity and specificity for EV and 91% and 91.7% for HPeV, respectively. Of the 111 RV-A-positive stool specimens, 28 (25.2%) were EV-positive and 7 (6.3%) were HPeV-positive. No clinical differences between children with single or double infections were observed. DISCUSSION: In our study, the frequency of EV and HPeV infections was surprisingly high, thus underlining the importance of including EV and HPeV detection in diagnostic panels. The multiplex real-time RT-PCR presented in this paper can therefore be a useful method in a diagnostic setting.

Nod2 deficiency is associated with an increased mucosal immunoregulatory response to commensal microorganisms.

On the basis of previous studies demonstrating that a breach of the colonic epithelial barrier is associated with a microbiota-dependent increase in lamina propria (LP) regulatory cells, we investigated if the lack of spontaneous intestinal inflammation observed in nucleotide-binding oligomerization domain 2 (Nod2)-/- mice was due to enhanced intestinal regulatory function. We found that the LP CD4+ T-cell population of Nod2-/- mice contains an increased percentage of CD4+ regulatory T cells bearing transforming growth factor -ß/latency peptide (LP CD4+LAP (latency-associated peptide) + T cells) both under baseline conditions and following an intentional breach of the colonic barrier induced by ethanol administration. In addition, we found that Nod2-/- mice manifest decreased severity of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis and that TNBS-colitis in Nod2-/- or Nod2+/+ mice is ameliorated by adoptive transfer of LP cells from ethanol-treated mice before, but not after, depletion of LAP+ T cells. This increased regulatory T-cell response in Nod2-/- mice could explain why NOD2 polymorphisms in humans are not in themselves sufficient to establish inflammatory lesions.