The effect of a financial incentive on COVID-19 vaccination uptake, and predictors of uptake, in people experiencing homelessness: A randomized controlled trial.

People who are homeless are at increased risk of COVID-19 infection, and of poorer associated outcomes. Delivering vaccinations to, and ensuring uptake of multiple doses in, people who are homeless is complex. Financial incentives may improve vaccination uptake, particularly in people who have not received routine vaccinations previously, though evidence about the effect of incentives is limited and variable. This randomized controlled trial (ANZCTR 383156) assessed the effect of a financial incentive (an A$10 grocery voucher) on uptake of the second COVID-19 vaccination in Australian adults who were homeless, and who had received their first dose. Participants were recruited through a vaccination program for people experiencing homelessness between September 2021 and January 2022. They were followed-up for a minimum of 6.5 months. Uptake was measured 'on-time' at 6 weeks, and at any time during the trial period. Vaccination status was checked on the Australian Immunisation Register. Demographic and vaccination program characteristics associated with uptake were also investigated. Eighty-six people consented to participate, and 43 were randomly allocated to each of the 'incentive' and 'no incentive' groups. The incentive slightly increased the likelihood of a participant receiving a second vaccination on-time (risk difference (RD), 11.6 % [95 %CI, -9.0, 32.2 %]; p = 0.27), and at any time during the trial (RD, 14.0 % [95 %CI, -2.2, 30.1 %], p = 0.09). The incentive had a significant positive effect on uptake in people with no previous vaccination history, increasing their likelihood of receiving a second vaccination on-time (RD, 42.3 % [95 %CI, 15.7, 68.8 %]; p = 0.002) and at any time during the trial (RD, 38.7 % [95 %CI, 16.1, 61.3 %], p < 0.001). Financial incentives may increase COVID-19 vaccination uptake in people who are homeless, and particularly those who have no previous vaccination history. Future research should consider alternative incentive values, types, and cost-effectiveness.

The effect of spanning external fixation on entrapped structures in tibial pilon fractures.

PURPOSE: Pilon fractures are often complex injuries involving severe soft tissue injury. Studies have shown pilon fractures may entrap soft tissue structures between fracture fragments. Staged fixation of pilon fractures with spanning external fixation (SEF) is important for soft tissue rest and plays an important role in the management of these injuries. While SEF has been shown to promote soft tissue rest prior to definitive fixation, no studies have shown the effect SEF has on entrapped structures (ES). The purpose of this study was to evaluate how SEF effects ES in pilon fractures. METHODS: A retrospective review of 212 pilon fractures treated at our institution between 2010 and 2022 was performed. Patients with a CT scan pre-SEF and post-SEF met inclusion criteria. CTs were reviewed to characterize ES in pre- and post-SEF imaging. RESULTS: Of the 19 patients with ES identified on CT pre-SEF, seven (36.8%) had full release of ES post-SEF and 12 (63.2%) had no release of ES. The posterior tibial tendon was the most commonly ES and remained entrapped in 62.5% of cases. Only 25% of 43-C3 fractures had release of ES post-SEF, while 100% of 43-C1 and 43-C2 fractures demonstrated complete release of ES post-SEF. CONCLUSION: Entrapped structures in pilon fractures are likely to remain entrapped post-SEF, with only one-third of our cohort demonstrating release. In 43-C3 patterns, if ES are identified on CT pre-SEF, surgeons should consider addressing these either through mini open versus open approaches at the time of SEF as they are likely to remain entrapped post-SEF.

Self-pacing ameliorates recall deficit when listening to vocoded discourse: a cochlear implant simulation.

Introduction: In spite of its apparent ease, comprehension of spoken discourse represents a complex linguistic and cognitive operation. The difficulty of such an operation can increase when the speech is degraded, as is the case with cochlear implant users. However, the additional challenges imposed by degraded speech may be mitigated to some extent by the linguistic context and pace of presentation. Methods: An experiment is reported in which young adults with age-normal hearing recalled discourse passages heard with clear speech or with noise-band vocoding used to simulate the sound of speech produced by a cochlear implant. Passages were varied in inter-word predictability and presented either without interruption or in a self-pacing format that allowed the listener to control the rate at which the information was delivered. Results: Results showed that discourse heard with clear speech was better recalled than discourse heard with vocoded speech, discourse with a higher average inter-word predictability was better recalled than discourse with a lower average inter-word predictability, and self-paced passages were recalled better than those heard without interruption. Of special interest was the semantic hierarchy effect: the tendency for listeners to show better recall for main ideas than mid-level information or detail from a passage as an index of listeners' ability to understand the meaning of a passage. The data revealed a significant effect of inter-word predictability, in that passages with lower predictability had an attenuated semantic hierarchy effect relative to higher-predictability passages. Discussion: Results are discussed in terms of broadening cochlear implant outcome measures beyond current clinical measures that focus on single-word and sentence repetition.

Congruent Prosody Reduces Cognitive Effort in Memory for Spoken Sentences: A Pupillometric Study with Young and Older Adults.

BACKGROUND: In spite of declines in working memory and other processes, older adults generally maintain good ability to understand and remember spoken sentences. In part this is due to preserved knowledge of linguistic rules and their implementation. Largely overlooked, however, is the support older adults may gain from the presence of sentence prosody (pitch contour, lexical stress, intra-and inter-word timing) as an aid to detecting the structure of a heard sentence. METHODS: Twenty-four young and 24 older adults recalled recorded sentences in which the sentence prosody corresponded to the clausal structure of the sentence, when the prosody was in conflict with this structure, or when there was reduced prosody uninformative with regard to the clausal structure. Pupil size was concurrently recorded as a measure of processing effort. RESULTS: Both young and older adults' recall accuracy was superior for sentences heard with supportive prosody than for sentences with uninformative prosody or for sentences in which the prosodic marking and causal structure were in conflict. The measurement of pupil dilation suggested that the task was generally more effortful for the older adults, but with both groups showing a similar pattern of effort-reducing effects of supportive prosody. CONCLUSIONS: Results demonstrate the influence of prosody on young and older adults' ability to recall accurately multi-clause sentences, and the significant role effective prosody may play in preserving processing effort.

Strategic Pauses Relieve Listeners from the Effort of Listening to Fast Speech: Data Limited and Resource Limited Processes in Narrative Recall by Adult Users of Cochlear Implants.

Speech that has been artificially accelerated through time compression produces a notable deficit in recall of the speech content. This is especially so for adults with cochlear implants (CI). At the perceptual level, this deficit may be due to the sharply degraded CI signal, combined with the reduced richness of compressed speech. At the cognitive level, the rapidity of time-compressed speech can deprive the listener of the ordinarily available processing time present when speech is delivered at a normal speech rate. Two experiments are reported. Experiment 1 was conducted with 27 normal-hearing young adults as a proof-of-concept demonstration that restoring lost processing time by inserting silent pauses at linguistically salient points within a time-compressed narrative ("time-restoration") returns recall accuracy to a level approximating that for a normal speech rate. Noise vocoder conditions with 10 and 6 channels reduced the effectiveness of time-restoration. Pupil dilation indicated that additional effort was expended by participants while attempting to process the time-compressed narratives, with the effortful demand on resources reduced with time restoration. In Experiment 2, 15 adult CI users tested with the same (unvocoded) materials showed a similar pattern of behavioral and pupillary responses, but with the notable exception that meaningful recovery of recall accuracy with time-restoration was limited to a subgroup of CI users identified by better working memory spans, and better word and sentence recognition scores. Results are discussed in terms of sensory-cognitive interactions in data-limited and resource-limited processes among adult users of cochlear implants.

An Early-Stage Colon Cancer Develops Intrabiliary Growth Type Metastasis 7 Years After Curative Colectomy.

Although liver metastasis commonly occurs in patients with colorectal cancer (CRC), it is infrequent that it presents several years after curative resection for early-stage disease. Even more unusual is development of intrabiliary growth type metastasis rather than parenchymal metastasis. When this occurs, it can be mistaken for cholangiocarcinoma. We present a case in a patient with history of pT1N0M0 CRC treated with sigmoidectomy 7 years previously who presented with abdominal pain and MRI revealing left hepatic ductal dilation with no accompanying mass. With a recent normal colonoscopy and carcinoembryonic antigen, he was diagnosed with cholangiocarcinoma. Anatomic hepatic resection was performed, and final pathology with immunohistochemistry revealed staining consistent with CRC metastasis rather than cholangiocarcinoma. Intrabiliary growth type metastasis is a rare occurrence, which leads to its misdiagnosis. Patients with an intrabiliary tumor and a history of CRC should have immunohistochemistry to confirm the diagnosis to ensure appropriate adjuvant treatment and counseling.

How often does the preoperative plan for freehand pedicle screw placement match the actual surgical execution in adolescent idiopathic scoliosis?

PURPOSE: To provide a baseline for comparison with future advancements, this study determined the accuracy of preoperative planning of pedicle screw placement using standard radiographs for posterior fusion (PSF) for adolescent idiopathic scoliosis (AIS). METHODS: Ninety-five patients with AIS planned for PSF were prospectively enrolled. Preoperative planning was based upon standard upright posteroanterior and lateral radiographs. The planned number of screws to be placed at each level was recorded. Intraoperatively, all screws were placed by freehand technique. The number of successfully placed screws and the reasons for abandoning screw placement were documented. RESULTS: There were a total of 1783 pedicle screws planned preoperatively. The average planned implant density was 2.0 implants/vertebra. A total of 1723 (96.6%) of the planned screws were placed successfully. Fourteen (0.8%) screws were abandoned after attempted placement (range 0-2 screws/case). Of 241 screws planned in pedicles noted to be "hypoplastic," 13 resulted in the use of a hook or no instrumentation. The placement was not attempted for 49 (range 0-7/case) planned screws due to intraoperative decision-making and a sense that the curve was flexible enough not to require every screw. Three cases (3.2%) required instrumentation of an additional level. CONCLUSIONS: Standard spine radiographs allow for accurate preoperative planning for freehand pedicle screw placement in AIS. Ninety-seven percent of planned screws were placed successfully. The primary reason for deviation from the preoperative plan was intraoperative surgeon decision-making rather than difficulty with screw placement. This study will serve as a baseline when considering the utilization of navigation in PSF for AIS.

The Effect of Goal-Directed Fluid Administration on Outcomes After Pancreatic Surgery.

BACKGROUND: We evaluated the effect of an Enhanced Recovery After Surgery protocol on intraoperative fluid administration and postoperative outcomes in pancreatic surgery. METHODS: Pancreatic cancer resections at our institution from 2012 to 2018 were grouped according to pre- or post-protocol initiation. Preoperative characteristics and postoperative outcomes were compared with Fisher's exact test and chi-square for categorical variables, and Mann-Whitney U test for continuous variables. Further analysis separated patients that had a Whipple from those who had distal pancreatectomy. RESULTS: A total of 263 patients underwent pancreatic cancer resection during the study period (169 Whipples, 84 DPs, 92 pre-ERAS and 171 post-ERAS). Intraoperative fluid administration significantly decreased after protocol implementation (mean 6,277 ml vs. 3870 ml, p < 0.001). This held true when separating patients that had a Whipple procedure from those that had a DP (6,929 ml vs. 4,513 ml, p < 0.001, 5,060 ml vs. 2,833 cc, p = 0.002, respectively). Intensive care unit (ICU) admission (41.3% vs. 20.5%, p < 0.001) and length of stay (9.4 vs. 8.1 days, p < 0.01) were significantly reduced after ERAS implementation for all patients and in Whipple patients alone (47.5% vs. 23.6%, p = 0.002 and 10.7 vs. 6.6 days, p = 0.004). DP patients also had significantly decreased ICU admissions (41.3% vs. 20.5%, p = 0.045). All other postoperative outcomes were not significantly different. CONCLUSION: For patients undergoing pancreatic cancer resection, goal-directed fluid management is associated with decreased intraoperative fluid administration, decreased ICU admission, and decreased length of stay without an increase in postoperative complications or readmission.

Tranexamic Acid Associated With Less Wound Complications in Ankle and Hindfoot Surgery: Level III, Retrospective Cohort Study.

INTRODUCTION: The purpose of this study was to determine whether total ankle arthroplasty (TAA) and ankle/hindfoot fusion patients receiving tranexamic acid (TXA) exhibit fewer wound complications. METHODS: A retrospective review was conducted of 212 patients (217 feet) undergoing TAA (n = 72), ankle (n = 36), tibiotalocalcaneal (n = 20), pantalar (n = 1), or hindfoot fusion (ie, subtalar = 47, double = 33, and triple = 8) between 2015 and 2020 by a fellowship-trained foot and ankle surgeon at an academic medical center. Demographics, medical history, complications, and union status were compared between TXA (n = 101) and non-TXA (n = 116) cohorts. The mean follow-up was 1.24 years (range, 0.25 to 4.68). RESULTS: The TXA group had significantly less postoperative infections (5.9% versus 15.5%, P = 0.025). Within a subgroup analysis of ankle/hindfoot fusions, the TXA group exhibited significantly more Charcot neuroarthropathy (20.7% versus 5.7%, P = 0.006) and shorter follow-up duration (0.96 versus 1.30 years, P = 0.030); however, TXA was associated with shorter time to fusion (146 versus 202 days, P = 0.049) and fewer revision surgeries (8.6% versus 21.8%, P = 0.036). Subgroup analysis excluding feet with Charcot also demonstrated less postoperative infections (4.5% versus 14.4%, P = 0.020). Subgroup analysis of TAAs showed fewer cases of superficial infections (2.3% versus 27.6%, P = 0.002) and delayed wound healing (25.6% versus 48.3%, P = 0.047) in the TXA cohort. DISCUSSION: TXA use in ankle/hindfoot surgery was correlated with a reduction in superficial infections and radiographic time to union. The use of TXA in TAA correlated with fewer superficial infections and cases of delayed wound healing. Thus, in addition to other areas of orthopaedics, TXA seems to be beneficial in hindfoot and ankle surgery. DATA AVAILABILITY AND TRIAL REGISTRATION NUMBERS: All data were obtained from our institution's medical records. This study is not associated with a clinical trial.

Sauvé-Kapandji and Darrach Salvage Procedure Rates and Perioperative Parameters for Distal Radioulnar Joint Arthritis and Instability.

BACKGROUND: Distal radioulnar joint (DRUJ) instability and arthritis are often painful and functionally limiting pathologies. Two common salvage procedures for DRUJ dysfunction are the Darrach and Sauvé-Kapandji (S-K) procedures. This study aims to provide an analysis of national Darrach and S-K procedure utilization rates and patient demographics. METHODS: A national ambulatory surgery database, the 2018 Nationwide Ambulatory Surgery Sample, was filtered for Darrach and S-K procedure encounters. Data related to patient demographics and medical history, indications for DRUJ salvage, and concurrent hand/wrist procedures were collected. RESULTS: Database analysis revealed 1044 Darrach and 223 S-K procedure encounters. Patients undergoing Darrach procedures were older (60 vs 57, P = .002) and more likely to be women (66.1% vs 54.6%, P < .05). Patients aged <35 years underwent S-K procedures at greater rates compared with Darrach (13.9% vs 8.6%, P < .05). Primary osteoarthritis proved to be the most common indication for DRUJ salvage (64.8%) compared with rheumatoid arthritis (23.2%) and post-traumatic osteoarthritis (12.0%). Darrach and S-K procedures were accompanied by a secondary procedure at rates of 64% and 41%, respectively. The most common secondary procedures were tendon transfer, implant removal, neuroplasty, nerve resections, and wrist arthroscopy. CONCLUSIONS: Patient age and sex are associated with DRUJ salvage procedure selection. Sauvé-Kapandji procedures are used in higher rates in male and younger patient populations. Furthermore, primary osteoarthritis and rheumatoid arthritis are the main underlying pathologies for Darrach and S-K procedures.

Use of Small-Pin Distraction and Low-Speed, High-Torque Burring for Talar Osteochondral Allografts: Technique Tip.

Level of Evidence: Level V, expert opinion.

Fulminant myocarditis as an early presentation of SARS-CoV-2.

Myocarditis is well known to be caused by viral infections such as Coxsackie virus group B, human herpes virus 6 and parvovirus B19. However, during the current emerging outbreak of SARS-CoV-2, there have been few case reports describing myocarditis as a possible presentation. In our case report we describe, early cardiac manifestations of SARS-CoV-2 in a UK District General Hospital. A 44-year-old Caucasian woman without any comorbidities presented with SARS-CoV-2 related fulminant myocarditis without initial respiratory symptoms. Patient underwent treatment with milrinone and methylprednisolone that showed reduction in myocardial inflammation and significantly improved myocardial contractility. This was then followed by a second phase of SARS-CoV-2 associated pneumonia and renal failure requiring ventilatory support and haemofiltration. Although, not described in the literature, we have found conjunctive use of milrinone and methylprednisolone effective in patient with SARS-CoV-2 fulminant myocarditis.

Antiphospholipid syndrome in a patient with rheumatoid arthritis.

Antiphospholipid syndrome (APS) is an autoimmune condition characterized by a thrombotic event and/or pregnancy morbidity in the presence of persistently elevated antiphospholipid (aPL) antibody titers, which are most prevalent in patients with systemic lupus erythematosus but also have been associated with other autoimmune, malignant, and infectious diseases. In contrast to the clear correlation between high aPL antibody titers and thrombotic events in patients with systemic lupus erythematosus, the pathogenic role of these autoantibodies in association with other diseases, such as rheumatoid arthritis (RA), is not as well defined. We report a case of APS manifesting as cutaneous ulceration and necrosis in a patient with severe RA.

Comparison of Cemented and Bone Ingrowth Fixation Methods in Hip Resurfacing for Osteonecrosis.

BACKGROUND: The optimal surgical treatment for osteonecrosis of the femoral head has yet to be elucidated. To evaluate the role of femoral fixation techniques in hip resurfacing, we present a comparison of the results for 2 consecutive groups: group 1 (75 hips) received hybrid hip resurfacing implants with a cemented femoral component; group 2 (103 hips) received uncemented femoral components. Both groups received uncemented acetabular components. METHODS: We retrospectively analyzed our clinical database to compare failures, reoperations, complications, clinical results, metal ion test results, and X-ray measurements. Using consecutive groups caused time interval bias, so we required all group 2 patients to be at least 2 years out from surgery; we compared results from 2 years and final follow-up. RESULTS: Patient groups matched similarly in age, body mass index, and percent female. Despite similar demographics, the uncemented, group 2 cases showed a lower raw failure rate (0% vs 16%; P < .0001), a lower 2-year failure rate (0% vs 7%; P = .04), and a superior 8-year implant survivorship (100% vs 91%; log-rank P = .0028; Wilcoxon P = .0026). In cases that did not fail, patient clinical (P = .05), activity (P = .02), and pain scores (P = .03), as well as acetabular component position (P < .0001), all improved in group 2, suggesting advancements in surgical management. There were no cases of adverse wear-related failure in either group. CONCLUSION: This study demonstrates a superior outcome for cases of osteonecrosis with uncemented hip resurfacings compared to cases employing hybrid devices.

Macrophage-derived IL-6 contributes to ANG II-mediated angiotensinogen stimulation in renal proximal tubular cells.

The development of ANG II-dependent hypertension involves increased infiltration of macrophages (MΦ) and T cells into the kidney and the consequent elevation of intrarenal cytokines including IL-6, which facilitates the progression of hypertension and associated kidney injury. Intrarenal renin-angiotensin system (RAS) activation, including proximal tubular angiotensinogen (AGT) stimulation, has also been regarded as a cardinal mechanism contributing to these diseases. However, the interaction between immune cells and intrarenal RAS activation has not been fully delineated. Therefore, the present study investigated whether ANG II-treated MΦ induce AGT upregulation in renal proximal tubular cells (PTCs). MΦ were treated with 0-10(-6) M ANG II for up to 48 h. PTCs were incubated with the collected medium from MΦ. In ANG II-treated MΦ, IL-6 mRNA and protein levels were increased (1.86 ± 0.14, protein level, ratio to control); moreover, IL-6 levels were higher than TNF-α and IL-1ß in culture medium isolated from ANG II-treated MΦ. Elevated AGT expression (1.69 ± 0.04, ratio to control) accompanied by phosphorylated STAT3 were observed in PTCs that received culture medium from ANG II-treated MΦ. The addition of a neutralizing IL-6 antibody to the collected medium attenuated phosphorylation of STAT3 and AGT augmentation in PTCs. Furthermore, a JAK2 inhibitor also suppressed STAT3 phosphorylation and AGT augmentation in PTCs. These results demonstrate that ANG II-induced IL-6 elevation in MΦ enhances activation of the JAK-STAT pathway and consequent AGT upregulation in PTCs, suggesting involvement of an immune response in driving intrarenal RAS activity.

Limb-Threatening Arterial Thrombosis in a Patient with Eosinophilic Granulomatosis with Polyangiitis.

Eosinophilic granulomatosis (EGPA), or Churg-Strauss syndrome, is a rare and necrotizing systemic vasculitis, which affects small-to-medium-sized vessels and often manifests with severe asthma and eosinophilia. We report a case of a 72 year-old male with a two-year lung-biopsy proven history of EGPA who presented with retiform purpura and patchy necrosis on his bilateral shins, which progressed to sharply demarcated, stellate ulcerations with surrounding erythema within two weeks. Laboratory work up revealed elevated anti-Cardiolipin IgM, rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein, although P-neutrophil cytoplasmic antibody (P-ANCA) and C-neutrophil cytoplasmic antibody (C-ANCA) were negative. Vascular studies revealed long anterior tibial and dorsalis pedis artery occlusion and severe small vessel disease in plantar digital arteries. Despite treatment with intravenous cyclophosphamide, pulse-dose methylprednisolone, and pentoxifylline, the patient experienced disease progression and limb threatening arterial thrombosis. This case highlights the importance of vascular and neuropathic sequelae that may result from untreated or undertreated EGPA in P-ANCA-negative patients without active pulmonary symptoms.

Confetti-like depigmentation: A potential sign of rapidly progressing vitiligo.

BACKGROUND: Confetti-like depigmentation was noted in patients reporting recent worsening of vitiligo. OBJECTIVE: We sought to determine if confetti-like depigmentation is a marker of rapidly progressing vitiligo. METHODS: Review of patient records and images of patients from a vitiligo registry resulted in 7 patients with 12 images that fit inclusion criteria and were evaluated for percent depigmentation by 3 independent reviewers. The Vitiligo Disease Activity Score and the Koebner Phenomenon in Vitiligo Score in an additional cohort of patients with confetti-like lesions were compared with patients who had vitiligo without confetti-like lesions. RESULTS: The mean percentage of depigmentation at baseline was 19.2%, which increased to 43.9% in images obtained at a mean of 16 weeks of follow-up. Vitiligo Disease Activity Score and Koebner Phenomenon in Vitiligo Score were significantly higher in the patients with confetti-like lesions compared with those without confetti-like lesions. A skin biopsy specimen of a confetti-like lesion in 1 patient revealed an inflammatory infiltrate in the papillary dermis with CD8(+) T cells localized to the dermoepidermal junction. LIMITATIONS: Small, single-center retrospective review and lack of full-body photographs are limitations. CONCLUSIONS: A confetti-like pattern of depigmentation may be a negative prognostic indicator for patients with rapidly progressing vitiligo. Further, prospective studies to evaluate this physical finding should be performed.

Granulomatous dysimmune reactions (sarcoidosis, granuloma annulare, and others) on differently injured skin areas.

Granulomatous disorders are chronic cell-mediated immune responses histologically characterized by collections of macrophages, epithelioid cells, and multinucleated giant cells. This disease spectrum often has an infectious origin, but sometimes neither an infective agent nor an inciting antigenic stimulus can be identified. The skin may be a preferential target for these disorders, especially in the areas that have been damaged by various forms of skin injury (eg, herpetic infections, trauma, thermal or solar burns, vaccinations, tattoos). These damaged skin sites frame the new concept of an immunocompromised cutaneous district (ICD), which defines a skin area with acquired immune dysregulation that can pave the way for the local onset of opportunistic disorders, such as infections, tumors, and granulomatous disorders. Sarcoidosis, granuloma annulare (GA), and forms of granulomatous vasculitis, such as Churg-Strauss syndrome (CSS) and Wegener's granulomatosis (WG), are the most common granulomatous disorders that occur in an ICD and may share common pathogenic mechanisms. Recent studies have found clinical and pathologic overlapping features across noninfectious granulomas. Although no unifying etiology exists, the development of granulomatous processes in the ICD has often been reported and the literature contains various hypotheses to explain it: (1) overactive immune response in a previously injured region with or without loss of immune tolerance; (2) overall reduced immune response; (3) retention of an exogeneous antigen or foreign body; (4) altered neural signaling; and (5) a combination of all the aforementioned processes. T helper cells, T regulatory cells, and macrophages, as well as a number of antigenic proteins, have been identified as potential contributing factors. In addition, a genetic predisposition and an intact systemic immune system are both instrumental for the persistence of local granuloma formation in the ICD.