Lumbopelvic shortening and local host bone-to-host bone reconstruction: a surgical method for lumbopelvic fusion following total sacrectomy.

PURPOSE: Primary sacral tumors are rare, representing fewer than 7% of spinal neoplasms. Following total sacrectomy, lumbopelvic instrumentation and fusion carries a high risk of non-union with no current consensus on fixation techniques to augment bony defects. We aim to describe the outcome of a reconstruction technique following total sacrectomy whereby lumbopelvic shortening is performed and the posterior pelvic ring is compressed to enable contact with the native L5 vertebra. METHODS: Retrospective chart review of 2 patients with 2 and 7 years post-operative follow-up. A review of hospital records including clinical assessments, complications, pathology and imaging reports. RESULTS: Patient 1 was a 17-years-old male with recurrent sacral chondrosarcoma, who presented with lumbosacral neuropathic pain and radiculopathy after failed intralesional surgery. Patient 2 was a 51-years-old male with chronic low back pain caused by a large low-grade chondroid sacral chordoma. Reconstruction technique involved mobilizing the L5 vertebra into the pelvis and pelvic ring closure to obtain host-bone-to-bone contact, eliminating the need for alternative grafts. Post-operative complications included superficial abdominal wound drainage, lower limb DVT, pulmonary emboli and deep pelvic infection. Serial CT scans demonstrated bony fusion in both patients. Neither patients had evidence of tumor recurrence and were able to ambulate at recent follow-up. Imaging demonstrated changed acetabular version of - 4.6/- 8.1 and - 14.4/- 14.8 (patient 1/2, R/L, respectively). CONCLUSION: Primary lumbopelvic shortening represents an alternative local autograft reconstructive technique for management of large sacral defects following total sacrectomy. This technique obviates the additional morbidity and surgical cost associated with the use of previously described techniques.

The Characteristics and Outcomes of Patients Who Make an Emergency Department Visit for Hypertension After Use of a Home or Pharmacy Blood Pressure Device.

STUDY OBJECTIVE: Emergency department (ED) visits for hypertension are rapidly increasing. Hypertension guidelines began recommending use of self-measurement blood pressure (BP) devices in the early 2000s, which could be contributing to the increase. We aim to examine the proportion of ED visits for hypertension that occurred after a BP measurement with a self-measuring device, and the associated outcomes. METHODS: This retrospective observational study included adults who made an ED visit and received a primary diagnosis of hypertension at 1 of 5 community and tertiary hospitals in Ontario, Canada, between April 2010 and March 2011. We categorized ED visits into 4 groups: those made after a home BP reading, a pharmacy reading, as a result of a physician referral, and all others (termed "not documented"). We examined rates of admission to the hospital, ED treatment (administration of antihypertensive medication and prescription provision), and post-ED clinical events (follow-up care, return ED visits, and long-term all-cause mortality) by group. RESULTS: Among 1,508 qualifying patients, median presenting ED BP was 182/97 mm Hg (interquartile range 164 to 200/85 to 109 mm Hg). The percentage of patients who presented to the ED after a reading at home, at a pharmacy, or by physician referral and the remaining patients not documented was 40.9%, 8.3%, 13.3%, and 37.5%, respectively. Overall, 109 patients (7.2%) were admitted to the hospital. The proportion of patients admitted after a home or pharmacy reading, after a physician referral, or who were not documented was 3.1%, 11.9%, and 11.0%, respectively. Two-year mortality rates were 5.4%, 0.0%, 6.5%, and 5.3% for the home, pharmacy, physician referral, and not documented groups, respectively. Among the 92.8% of patients who were discharged from the ED, 11% made another ED visit for hypertension within a year. CONCLUSION: In this study, half of patients with an ED visit that was primarily for hypertension presented after elevated readings on self-measurement devices. Only 3% of these patients were admitted to the hospital.

Familial Chiari malformation: a systematic review and illustrative cases.

OBJECTIVE: Chiari malformations (CMs) are a group of congenital or acquired disorders characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa. CM is considered largely sporadic-however, there exists growing evidence of transmissible genetic underpinnings. The purpose of this systematic review of all familial studies of CM was to investigate the existence of an inherited component and provide recommendations to manage and monitor at-risk family members. METHODS: This paper includes the following: 1) a unique case report of dizygotic twins who presented at the Toronto Western Hospital Spinal Cord Clinic with symptomatic CM type 1 (CM-1) and syringomyelia; and 2) a systematic review of familial CM. The EMBASE and MEDLINE databases were searched on June 27, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only articles in the English language concerning the diagnosis of CM in > 1 human family member presented as a case study, case series, or literature review were included. RESULTS: Among the 29 articles included in the final analysis, a total of 34 families with CM were analyzed. An average of 3 cases of CM were found per family among all generations. Eighty-one cases (88%) reported CM-1, whereas the other 11 (12%) cases reported either CM-0, CM-1.5, or tonsillar ectopia. A syrinx was present in 37 (54%) cases, with 14 (38%) of these patients also reporting a skeletal abnormality, the most common comorbidity. Most family members diagnosed with CM were siblings (18; 35%), followed by monozygotic twins/triplets (12; 23%). CONCLUSIONS: Patients most often presented with headaches, sensory disturbances, or generalized symptoms. Overall, there exists mounting evidence for a hereditary component of CM. It is unlikely to be explained by a classic mendelian inheritance pattern, but is rather a polygenic architecture influenced by variable penetrance, cosegregation, and entirely nongenetic factors. For first-degree relatives of those affected by CM, the authors' findings may influence clinicians to conduct closer clinical and radiographic monitoring, promote patient education, and consider earlier genetic testing.

Distal Lumbar Lordosis is Associated With Reoperation for Adjacent Segment Disease After Lumbar Fusion for Degenerative Conditions.

STUDY DESIGN: A single centre retrospective review. OBJECTIVE: Recent studies have suggested that distal lordosis (L4-S1, DL) remains constant across all pelvic incidence (PI) subgroups, whilst proximal lordosis (L1-L4, PL) varies. We sought to investigate the impact of post-operative DL on adjacent segment disease (ASD) requiring reoperation in patients undergoing lumbar fusion for degenerative conditions. METHODS: Patients undergoing 1-3 level lumbar fusion with the two senior authors between 2007-16 were included. Demographic and radiographic data were recorded. Univariate, multivariate binary logistic regression, and Kaplan Meier survivorship analyses were performed. RESULTS: 335 patients were included in the final analysis. Most had single (67%) or two (31%) level fusions. The mean follow-up was 64-month. Fifty-seven patients (17%) underwent reoperation for ASD at an average of 78-month post-operatively (R group). The R group had a significantly lower mean post-operative DL (27.3 vs 31.1 deg, P < .001) and mean PI (55.5 vs 59.2 deg, P < .05). On univariate analysis, patients with a post-operative DL of <35 deg had higher odds of reoperation for ASD than those with a post-operative DL of ≥35 deg (OR 2.7, P = .016). In the multivariate model, post-operative DL, low/average PI, and spondylolisthesis were all significantly associated with reoperation for ASD. CONCLUSION: This study provides preliminary support to an association between post-operative distal lumbar lordosis and risk of reoperation for ASD in patients undergoing fusions for degenerative conditions. Further multicentre prospective study is needed to independently confirm this association and identify the impact of restoration of physiological distal lumbar lordosis on long term patient outcomes.

Offloading Plantar Pressures in Healthy Adults: Stirrup Cast vs Total Contact Cast.

BACKGROUND: Diabetic foot ulcers are associated with significant morbidity and mortality while posing a challenge for healthcare professionals. Offloading is considered the mainstay of treatment. Total contact casting (TCC) is widely used but does not effectively offload the hindfoot. Some studies suggest that a metal stirrup is effective at offloading midfoot and hindfoot ulcers. The primary purpose of this study is to compare the offloading mechanism of TCC to a stirrup cast. METHODS: A pilot observational study assessing 12 healthy volunteers who underwent casting with a TCC or stirrup cast. A sensor (Pedar; Novel GmbH) that measures maximum force, peak pressure, and contact time and area of each foot region, was placed inside the cast to assess the offloading mechanisms of the 2 interventions. RESULTS: We measured a reduction in all plantar foot loading parameters from the TCC to the stirrup cast. The highest reductions of 85% to 96% (±5%-13%) were noted in maximum force and peak pressure under the forefoot (P < .0001) and found reductions in maximum force, the contact area of all regions of the foot, peak pressure and contact time of the forefoot and midfoot, and contact area of the hindfoot (P < .05). CONCLUSION: In this experimental trial of healthy adults, the stirrup cast was more effective than the TCC by offloading the foot mostly in the forefoot and midfoot.

Converting hip and knee arthroplasty cases to same-day surgery due to COVID-19.

AIMS: In 2020, the COVID-19 pandemic meant that proceeding with elective surgery was restricted to minimize exposure on wards. In order to maintain throughput of elective cases, our hospital (St Michaels Hospital, Toronto, Canada) was forced to convert as many cases as possible to same-day procedures rather than overnight admission. In this retrospective analysis, we review the cases performed as same-day arthroplasty surgeries compared to the same period in the previous 12 months. METHODS: We conducted a retrospective analysis of patients undergoing total hip and knee arthroplasties over a three-month period between October and December in 2019, and again in 2020, in the middle of the COVID-19 pandemic. Patient demographics, number of outpatient primary arthroplasty cases, length of stay for admissions, 30-day readmission, and complications were collated. RESULTS: In total, 428 patient charts were reviewed for October to December of 2019 (n = 195) and 2020 (n = 233). Of those, total hip arthroplasties (THAs) comprised 60% and 58.8% for 2019 and 2020, respectively. Demographic data was comparable with no statistical difference for age, sex, contralateral joint arthroplasty, or BMI. American Society of Anesthesiologists grade I was more highly prevalent in the 2020 cohort (5.1-times increase; n = 13 vs n = 1). Degenerative disc disease and fibromyalgia were less significantly prevalent in the 2020 cohort. There was a significant increase in same day discharges for non-direct anterior approach THAs (two-times increase) and total knee arthroplasty (ten-times increase), with a reciprocal decrease in next day discharges. There were significantly fewer reported superficial wound infections in 2020 (5.6% vs 1.7%) and no significant differences in readmissions or emergency department visits (3.1% vs 3.0%). CONCLUSION: The COVID-19 pandemic meant that hospitals and patients were hopeful to minimize the exposure to the wards, and minimize strain on the already taxed inpatient beds. With few positives during the COVID-19 crisis, the pandemic was the catalyst to speed up the outpatient arthroplasty programme that has resulted in our institution being more efficient, and with no increase in readmissions or early complications. Cite this article: Bone Jt Open 2021;2(7):545-551.

Relative antibacterial functions of complement and NETs: NETs trap and complement effectively kills bacteria.

Neutrophil extracellular traps (NETs) are web-like DNA structures released by activated neutrophils. These structures are decorated with antimicrobial proteins, and considered to trap and kill bacteria extracellularly. However, the exact functions of NETs remain elusive, and contradictory observations have been made with NETs functioning as an antimicrobial or a pathogentrapping mechanism. There is a disconnect in the interpretation of the involvement of other major immune mechanisms, such as the complement system, as effectors of the function of NETs. We have recently shown that NETs activate complement. In this study, we aimed to elucidate the relative antimicrobial roles of NETs in the absence and presence of complement. Using primary human neutrophils, human serum (normal, heat inactivated, and C5-depleted), P. aeruginosa (at multiplicity of infection, MOI, of 1 or 10), S. aureus (MOI of 1), colony-counting assays and confocal microscopy, we demonstrate that most bacteria trapped by NETs remain viable, indicating that NETs have limited bactericidal properties. By contrast, complement effectively killed bacteria, but NETs decreased the bactericidal ability of complement and degrading NETs by DNases restored complement-mediated killing. Experiments with conditions allowing for specific pathway activation showed that the complement classical and lectin, but not the alternative, pathway lead to bacterial killing. NETs under static conditions showed limited killing of bacteria while NETs under dynamic conditions showed enhanced bacteria trapping and reduced killing. Furthermore, NETs incubated with normal human serum depleted complement and reduced the hemolytic capacity of the serum. This report, for the first time, clarifies the relative bactericidal contributions of NETs and complement. We propose that - while NETs can ensnare bacteria such as P. aeruginosa - complement is necessary for efficient bacterial killing.

NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via Alternative and Non-alternative Pathways.

Neutrophils deposit antimicrobial proteins, such as myeloperoxidase and proteases on chromatin, which they release as neutrophil extracellular traps (NETs). Neutrophils also carry key components of the complement alternative pathway (AP) such as properdin or complement factor P (CFP), complement factor B (CFB), and C3. However, the contribution of these complement components and complement activation during NET formation in the presence and absence of bacteria is poorly understood. We studied complement activation on NETs and a Gram-negative opportunistic bacterial pathogen Pseudomonas aeruginosa (PA01, PAKwt, and PAKgfp). Here, we show that anaphylatoxin C5a, formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA), which activates NADPH oxidase, induce the release of CFP, CFB, and C3 from neutrophils. In response to PMA or P. aeruginosa, neutrophils secrete CFP, deposit it on NETs and bacteria, and induce the formation of terminal complement complexes (C5b-9). A blocking anti-CFP antibody inhibited AP-mediated but not non-AP-mediated complement activation on NETs and P. aeruginosa. Therefore, NET-mediated complement activation occurs via both AP- and non AP-based mechanisms, and AP-mediated complement activation during NETosis is dependent on CFP. These findings suggest that neutrophils could use their "AP tool kit" to readily activate complement on NETs and Gram-negative bacteria, such as P. aeruginosa, whereas additional components present in the serum help to fix non-AP-mediated complement both on NETs and bacteria. This unique mechanism may play important roles in host defense and help to explain specific roles of complement activation in NET-related diseases.

Characterization of a homolog of DEAD-box RNA helicases in Toxoplasma gondii as a marker of cytoplasmic mRNP stress granules.

Toxoplasma gondii is an obligate intracellular protozoan which infects one-third of the human population. Due to its high infection prevalence, Toxoplasma offers an ideal system for the study of host-parasite interaction. Similar to other eukaryotes, Toxoplasma maintains levels and localization of cytoplasmic mRNAs throughout its life cycle as part of a gene regulation network to meet all cellular and biochemical requirements. More recently, it was reported that the presence of cytoplasmic mRNA granules could contribute to the parasite pathogenesis and viability. Here we identified a novel Toxoplasma DEAD-box RNA helicase, referred to as Toxoplasma gondiiHomolog of DOZI (TgHoDI), because of its high homology (81%) to Plasmodium DOZI. TgHoDI is the functional ortholog of yeast DHH1, and its function was authenticated by complementation studies in Δdhh1 yeast strain. We demonstrated that TgHoDI is a marker of cytoplasmic RNA stress granules, which assemble when the parasites experience cellular stresses and translational arrest.