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Proboscis lateralis (PL) is a rare malformation, reported for the first time in 1861 by Forster in his monograph on congenital malformations of the human body. The abnormal side of the nose is represented by a tube-like rudimentary nasal structure, attached at any point along the embryonic fusion line between the anterior maxilla and the frontonasal processes. As clefts of the lip (and alveolus) are bilateral or unilateral, an arrhinia can be bilateral (total) or unilateral. In this case it is a 'hemi-arrhinia' (or heminasal agenesis. The arrhinias represent three groups of anomalies, each with different levels of clinical severity, some involving association with the labio-palatal cleft or agenesia of the premaxilla (1). In PL the nasal cavity on the affected side is replaced by a tubular appendage located off-center from the midline of the face, arising commonly from the medial aspect of the roof of the orbit (2). It is usually associated with heminasal aplasia or hypoplasia, microphthalmia, and — less commonly — with midline clefting. Associated brain and cranial vault anomalies are seen in 19% of these patients. PL is usually unilateral, with very few symmetrical/bilateral cases being reported (3). Morpho-aesthetic and psychological problems are frequent concerns for the patients and their families. In this study, the authors describe a clinical case and the chosen surgical technique, as well as reviewing the alternative techniques present in the literature. [ABSTRACT FROM AUTHOR]

Iraq–Iran war resulted in more than 400,000 people requiring prolonged medical care in Iran. An international team of prominent reconstructive surgeons led by Paul Tessier, the founder of craniofacial surgery, was invited to Iran during the war by official organizations entitled to support war victims. This team provided up-to-date oral and maxillofacial rehabilitation to patients with severe trauma defects in the lower third of the face. We collected the medical notes of 43 patients operated on by the Tessier team in Iran in the 1980s (files property of AFCF). The parameters we collected were: age of the patient, nature of the trauma (when available), previous procedures, number of implants placed (mandibular and maxillary), associated procedures (bone grafts, soft-tissue procedures, orthognathic surgery). A protocol based on soft-tissue rehabilitation using local flaps, parietal or iliac bone grafts and implant placement 6 months later was used in all patients. Paul Tessier's approach emphasizes the importance of keeping high standards of care in difficult situations and maintaining standard protocols. [ABSTRACT FROM AUTHOR]

Background Paul Tessier was a pioneering plastic surgeon who founded craniofacial surgery and had an international influence in the field of reconstructive surgery. We reviewed his techniques in the reconstruction of post-noma defects in Iran in the late 1970s. Patients and methods We studied a series of 23 patients operated on by Tessier from 1974 to 1978 in Iran (property of Association Française des Chirurgiens de la Face). They all suffered from noma in childhood with major facial defects. Results Ten suffered from simple lip and cheek defects, nine also from nose defects and four from extensive facial defects. Abbe flaps were used in 15 patients to reconstruct the lips completed by commissuroplasty in six patients. Nose defects were reconstructed with nasofrontal flaps (ten cases). The outer cheek was reconstructed with a rotation flap (four cases), or with a frontotemporal flap (six cases). The inner cheek was reconstructed using a Barron–Tessier myocutaneous flap (ten cases). Of the 23 patients, partial flap necrosis occurred in five cases. Conclusions Tessier was a pioneering plastic surgeon who used local flaps to reconstruct these important facial defects. He had a high rate of success, although nowadays local flaps are commonly replaced by free flaps. [ABSTRACT FROM AUTHOR]

Results: 3D motion analysis and performance data for the first five subjects are summarized in Figures 1 and 2. Circumduction area and kinematic path length (KPL) decreased sequentially with more restrictive splints (p < 0.01667). KPL showed a similar stepwise decline during both dart throwing and hammering, particularly with the elbow and forearm restricted. The coupling axis was consistent across all conditions tested. Dart throwing performance remained similar in the free and foam condition, but decreased in the hinged splint. A similar stepwise decline in function was observed with the elbow free and was most evident between the free and foam splinted conditions. Performance on the winding task remained similar between the free and foam splint conditions and decreased in the hinged splint. Interestingly, performance on the hammering task remained similar among all three conditions whether the elbow was restricted or unrestricted. Conclusion: 3D motion analysis can be utilized to objectively measure changes in complex coupled wrist motion. Functional performance is maintained through small decreases in wrist circumduction but declines with further decreases in circumduction area and KPL Coupled motion parameters may be better candidates than traditional measures of wrist motion for assessment of wrist functional ability, though the relationship between these parameters and wrist function may not be linear. This data is valuable for surgical planning where various surgical options result in different coupling path lengths and circumduction envelopes. Individualized treatment planning with the patient to identify unique functional needs can be incorporated into the clinical decision making process to determine which surgical intervention best fits the patient's functional requirements. Additionally, these measurements can track progress and predict return to work and sports. Purpose: To distinguish the effect of altered wrist motion on function during wrist specific functional tasks without the confounding factor of compensatory motions of the elbow and shoulder. Methods: Ten healthy subjects were recruited to perform wrist-specific functional tasks in three conditions: 1) free, 2) a partially restrictive foam splint, and 3) a severely restrictive hinged splint. Each task was performed while seated at a desktop with the elbow and forearm immobilized and while standing with the elbow and forearm unrestricted. 3D motion analysis was performed using 29 reflective markers and a twelve-camera motion capture system. Circumduction was described as the circumscribed area of motion, the circumference (kinematic path length) and orientation of the major axis (coupling axis). These parameters were recorded during maximal circumduction and during three functional tasks: dart throwing, hammering, and winding of thread around a spool. Functional performance measures for each task were also calculated. [ABSTRACT FROM AUTHOR]

Immunosuppressive myeloid cells in prostate cancer (PCa) are associated with disease progression and treatment resistance. Tumor-associated macrophages (TAMs) contribute to progression through suppression of anti-tumor immunity, remodeling of the tumor microenvironment (TME) and promoting tumor cell invasion and metastasis. SBRT is increasingly used for treatment of localized and metastatic PCa and promotes inflammatory remodeling of the TME. We examined irradiated human PCa in a cohort of patients that underwent pre-operative SBRT followed by prostatectomy (NCT03663218) to identify radiation-induced targets and validated findings in both in vitro and in vivo models. We performed 10X single-cell RNA sequencing (scRNA-seq) on prostatectomy specimens from men with high-risk localized PCa; 12,988 cells from 4 patients that underwent pre-operative SBRT and 47,314 cells from 6 patients that underwent prostatectomy alone. THP-1 monocytes polarized into macrophage states (M0, M1, M2, TAM) were used to characterize TREM2 expression and immune responses to radiation. In vivo studies with C57BL/6 mice inoculated with B6CaP flank tumors or PTEN-/-SPOPmutCHD1del organoid cell line were used to analyze intratumoral myeloid populations in response to SBRT (37.5Gy in 5 fractions). scRNA-seq analysis (Cell Ranger 7.1.0; Seurat v5 R package) revealed enrichment of a cluster of myeloid cells defined by a damage-associated Mɸ gene signature (TREM2, APOE, SPP1, LGALS3, CD9) in response to SBRT compared with non-irradiated specimens (35.6% vs 5.7%). Irradiation (20Gy x1) of THP-1 cells significantly increased TREM2 expression in M0 (p<0.01), M1 (p<0.001), and TAM (p<0.01) states. Conditioned media from irradiated THP-1 TAMs increased proliferation of PC3 tumor cells (p<0.0001) whereas CM (p<0.05) and protein lysate (p<0.001) derived from irradiated PC3 cells significantly increased TREM2 expression on M0-polarized THP-1 cells. In vivo studies with prostate SBRT in the organoid and B6CaP model both demonstrated significant irradiated tumor control (p<0.0001). TREM2 expression and sTREM2 levels were significantly increased in the irradiated TME (p<0.05) in both models as well as SPP1 expression in the B6CaP model. Immune profiling demonstrated robust myeloid infiltration in response to SBRT dominated by CD11b+F4/80+ TAMs in irradiated tumors. Furthermore, among irradiated tumors, TREM2 expression was markedly elevated in TAMs (organoid, p<0.0001) and TREM2 mean fluorescence intensity was significantly enriched among CD206+ TAMs in organoid (p< 0.001) and B6CaP (p<0.01) models. Preliminary findings in irradiated human PCa and subsequent validation studies in preclinical models suggest TREM2 defines a subset of radiation-induced TAMs. Ongoing work aims to characterize functional implications of radiation-induced TREM2 expression and whether TREM2 can be targeted to modulate radiation-induced immune responses. [ABSTRACT FROM AUTHOR]

Abstract: Transdifferentiation of stem cells into insulin-producing cells for the treatment of diabetes have shown promising but inconsistent results. We examined the potential for attracting bone marrow stem cells (BMSCs) to the pancreas using a chemokine, stromal cell-derived factor 1 (SDF-1). SDF-1 treatment markedly increased the number of GFP labeled BMSCs in the pancreas, but surprisingly, the majority was observed in liver. The liver cells had typical pancreatic endocrine cell gene expression including insulin I, insulin II, PDX-1, somatostatin, and glucagon. Combined treatment with SDF-1 and BMSC transplant reduced hyperglycemia and prolonged the long-term survival of diabetic mice, and a sub group had complete normoglycemia (<150mg/dl), restored blood insulin levels, and normal glucose tolerance. Our results suggest that SDF-1 could potentially be used to improve the homing of stem cells and β-cell regeneration. The mechanism appears to involve an increase in insulin producing cells mainly in the liver. [Copyright &y& Elsevier]

The new heart allocation system has decreased the priority status of durable LVADs, disincentivizing their use. New temporary catheter-based LVADs have emerged as a popular alternative bridge-to-transplant. The United Network for Organ Sharing (UNOS) database was queried for adult recipients of heart transplants listed in the new allocation system from October 18, 2018 to November 30, 2020. We included patients supported by continuous durable or temporary LVAD prior to transplant. We excluded patients with additional VADs, ECMO, multiorgan transplants, prior heart transplants, or loss to follow-up. Propensity matching 3:1 was performed for outcomes analysis. A total of 1232 patients met study criteria, 1030 patients with durable LVADs and 202 with temporary LVAD support. Consistent with the new allocation system, temporary LVAD patients spent less time on the waiting list (26.6 vs. 134.3 days, p<0.001). The majority of temporary LVADs were placed in regions 3 (15.3%), 4 (23.8%), and 5 (18.8%), while most durable LVAD cases came from regions 5 (11.7%), 10 (11.3%) and 11 (16.7%). Durable LVAD patients were more likely to receive hearts from donors with age >40 years (24.9% vs 17.3%, p=0.027), and donation after cardiac death (4.1% vs 0.0%, p=0.007). Temporary LVAD patients experienced 74% lower risk of death compared to durable LVAD patients in multivariate Cox regression (HR=0.26, 95% CI: 0.09-0.80, p=0.019) after adjusting for donor and recipient demographics and comorbidities, and regional differences. Similarly, overall survival was worse on Kaplan Meier analysis for durable LVAD patients in both the unadjusted (p=0.034) and propensity-matched models (p=0.049). In the post-allocation change era, the lower priority status of durable LVADs has resulted in centers turning to temporary devices. Our data suggest that in the new era, patients bridged to transplant with temporary LVAD may have a survival advantage. [ABSTRACT FROM AUTHOR]

The objective of this randomized clinical trial is to demonstrate that 2 treatments of real-time MRI-guided radiotherapy (RT) does not significantly increase patient-reported GI and GU symptoms compared to 5 treatments of RT 2 years after treatment completion (24 months). Key Eligibility Criteria: Inclusion Criteria 1. Men aged > 18 with histologically confirmed low or intermediate risk prostate cancer per NCCN guidelines. 2. ECOG 0 – 1 3. IPSS < 18 4. Ability to receive MRI-guided radiotherapy. 5. Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Exclusion Criteria 1. Prior history of receiving pelvic RT. 2. Patient with history of IBD. 3. Hip replacements. 4. History of bladder neck or urethral stricture. 5. TURP < 8 weeks prior to RT 6. Metastatic (pelvic nodal or distant) disease on CT, Bone, and/or PSMA PET scan. Study Design/Endpoints: This is a randomized phase II non-inferiority trial comparing 2 fractions of ultrahypofractionated RT (25 Gy total with optional PSMA/MRI boost to 28 Gy) versus 5 fractions of ultra-hypofractionated RT (37.5 Gy total with optional PSMA/MRI boost to 45 Gy) in the definitive setting for prostate cancer. Subjects will be stratified based on pre-specified stratification factors and randomized 1:1 to receive 2 or 5 fractions using permuted block randomization. The primary endpoint is the change in patient-reported GI and GU symptoms as measured by EPIC at 2 years from end of treatment. Secondary endpoints will include both the safety endpoints including change in GI and GU symptoms at 3, 6, 12 and 60 months from end of treatment, and multiple efficacy endpoints including time to progression, prostate cancer specific survival and overall survival. Sample Size: The sample size is calculated based on a non-inferiority design. The non-inferiority margins are set to be a change score of 6 points for the GI symptoms and 5 points for the GU symptoms. The standard deviations of the change scores are assumed to be 13.2 for the GI symptoms and 10.5 for the GU symptoms based on estimates generated in RTOG 0415 trial. This level of change in scores are deemed as clinically meaningful. For example, 6 points of change score for GI symptoms corresponds to two symptoms worsening by 1 level (i.e., loose stools and frequency of bowel movements change from "no problem" to "very small problem") or one of the symptoms worsening by 2 levels (i.e., loose stool change from "no problem" to "small problem"). A sample size of 122 with 61 in each arm will ensure 80% power for GI endpoint and 83% power for GU endpoint to detect non-inferiority using a one-sided two-sample t-test at the significance level of 0.05. Adjusting for a projected 10% EPIC/non-compliance rate, 136 patients (68 per arm) will be randomized. Stratification Factors: Patients will be stratified according to baseline EPIC bowel and urinary domain scores and country of treatment. Enrollment: Twenty patients. To be determined. To be determined. [ABSTRACT FROM AUTHOR]

The radiobiology of irradiated human prostate cancer (PCa) remains poorly understood as irradiated tissues often remain in situ. PREPARE-SBRT (NCT03663218) is a clinical trial testing the safety of neoadjuvant MRI-guided stereotactic body radiation therapy (SBRT) for men with high-risk PCa. We leveraged paired samples from pre-treatment biopsy and irradiated prostatectomy (RP) specimens to evaluate transcriptomic changes in irradiated tumors at acute timepoints following SBRT. Tumor RNA expression profiles were generated using Decipher GRID by Veracyte on 12 subjects enrolled on NCT03663218 with paired pre/post-SBRT tissues (n = 24). Descriptive statistics using Decipher Genomic Classifier (GC) Score [0-1] and GC risk group (low/int/high) were generated from a validated 22-gene GC. Tumor biology signatures reported as dichotomous variables evaluated changes in androgen receptor (AR) activity [higher v lower] and cell cycle progression (CCP) [lower v higher]. Decipher prostate subtype classifier [PSC, luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), basal neuroendocrine like (BN)] classification and PAM50 molecular subtype [luminal A (lumA), luminal B (lumB), basal] at pre/post-SBRT timepoints were reported. A control cohort of transcriptomic profiles of 803 matched untreated biopsy and RP samples from the same patients were used to control for signature differences attributable to sample type. The median pre- and post-SBRT GC scores were 0.55 and 0.72 (Δ+0.17), respectively. By comparison, median GC scores in a control cohort (n = 803) of biopsy and RP specimens were 0.50 and 0.56 (Δ+0.06), respectively. SBRT increased GC score in 9/12 subjects (75%) with a median increase of 0.3. Changes in GC score resulted in reclassification of baseline GC risk in 7 of 12 subjects with 71% of reclassified subjects (5/7) transitioning to a higher genomic risk. 92% of subjects (11/12) had higher AR activity scores at baseline. Of this subgroup, 5/11 (45%) converted to lower AR activity score after SBRT. CCP signatures remained stable in 9 of 12 subjects (75%) with 7/12 subjects exhibiting lower CCP score at baseline and only 1 subject transitioning from lower to higher CCP score. Distribution of PAM50 molecular subtype at baseline and after SBRT was lumA (33>53%), lumB (25>17%), basal (42>25%) resulting in 83% of subjects (10/12) annotated to a different PAM50 molecular subtype at pre/post-SBRT assessment. PSC subtype distribution at baseline was LD (33%), LP (25%), BI (33%) and BN (8%). Strikingly, after SBRT, 92% (11/12) of subjects were classified as BI molecular subtype with several immune activation signatures also increased after SBRT. A majority of subjects demonstrate a post-SBRT increase in GC score with reclassification of genomic-prognostic risk group in 58%. An enrichment of the basal-immune molecular subtype was observed following SBRT suggesting a convergence towards this biology in irradiated tumors. [ABSTRACT FROM AUTHOR]

Stereotactic body radiation therapy (SBRT) is a safe and effective treatment for localized prostate cancer (PCa). PREPARE-SBRT is a clinical trial testing the safety of neoadjuvant MRI-guided SBRT for men with high-risk localized PCa. We leveraged paired samples from pre-treatment biopsy and irradiated prostatectomy (RP) specimens to evaluate transcriptomic changes in irradiated tumors at acute time points following neoadjuvant SBRT. Tumor RNA expression profiles were generated using Decipher GRID by Veracyte on 12 subjects with paired pre- and post-SBRT tissues (n = 24). Descriptive statistics using gene expression profiles describing key biological features [DNA damage & repair (DDR), tumor proliferation, suppressed immune, activated immune, tumor microenvironment (TME)] and an exploratory analysis of RT sensitivity score with binary classification as sensitive or resistant were reported. A control cohort of transcriptomic profiles of 803 matched untreated biopsy and matching RP samples from the same subjects were used to control for signature differences attributable to sample type. Key tumor biology signatures most frequently observed were DDR (15/24), TME (11/24) and tumor proliferation (11/24). Signatures associated with tumor proliferation were disproportionately represented in pre-treatment samples (10/11) whereas TME-associated signatures were enriched predominantly in irradiated RP samples (8/11). Collectively, immune-related immune signatures skewed towards immune activation. All 3 samples annotated with suppressed immune signatures were from pre-treatment specimens whereas 75% (6/8) of samples annotated with activated immune status were from irradiated specimens. Additionally, conversion from suppressed to activated immune status was observed in 2 of 3 subjects (66%). In total, 42% of specimens (10/24) were designated as radio-resistant by RT sensitivity score. Among 8 baseline specimens annotated with RT resistant status, 75% of subjects (6/8) converted to RT sensitive status after neoadjuvant SBRT. Interestingly, in the two subjects with persistent radio-resistant status in pre- and post-samples there was associated with upregulation of TGF-β or PI3K-AKT pathway activation signatures. Pre- and post-SBRT transcriptomic signatures were heterogeneous and dynamic in a cohort of 12 patients with high-risk localized PCa highlighting the importance of studying longitudinal changes in individual patients. These data highlight an opportunity to leverage tumor RNA expression profiles to personalize patient and treatment selection and augment radiation response assessment. Clinical trials.gov ID (NCT03663218). [ABSTRACT FROM AUTHOR]

This study investigates reasons for rejection of hearts from Hepatitis C+ donors, and predictive factors for acceptance and transplantation. The United Network for Organ Sharing deceased donor registry was queried for adult donors with offers for heart donation from 2015-2020. We excluded patients from whom consent was not obtained or received, and incomplete data. HCV status was determined by nucleic acid testing (NAT). A total of 49,045 HCV- and 3,136 HCV+ donors were consented for heart donation from 2015-2020. HCV+ donors were younger (38.5 vs 43.5 years, p<0.001) with fewer comorbidities (p<0.001 for all): myocardial infarct (2.9% vs 4.6%), coronary artery disease (2.6% vs 7.0%), diabetes (6.3% vs 13.6%), and hypertension (23.9% vs 38.8%). The most common mechanism of death was stroke (30.1%) in HCV- donors and drug overdose (48.4%) in HCV+ donors. HCV+ donors were less likely to undergo recovery of the heart (20.0% vs 30.4%, p<0.001) and eventual transplantation (19.9% vs. 30.1%, p<0.001). HCV- organs were more often refused due to organ quality (HCV+: 21.0% vs HCV-:24.8%) or recovered and discarded (HCV+: 1.3% vs HCV-: 13.9%), while HCV+ hearts were more likely to be unused due to lack of recipient or accepting institution (25.0% vs 5.6%, p<0.001). Hepatitis was the primary reason for refusal in 12.2% of HCV+ donors. On multivariable analysis, HCV+ status was an independent negative predictor of acceptance and transplantation (OR 0.32, p<0.001). Negative predictors include age (OR 0.93, p<0.001), history of MI (OR 0.53, p<0.001), coronary artery disease (OR 0.11, p<0.001), diabetes (OR 0.57, p<0.001), smoking history (OR 0.84, p<0.001), chest trauma (OR 0.82, p<0.001), and cardiovascular mechanism of death (OR 0.71, p<0.001). HCV+ hearts were less likely to be recovered and transplanted despite lower rates of cardiovascular comorbidities. Reasons for discard were primarily unrelated to organ quality or function, and may reflect ongoing skepticism in use of HCV+ organs. [ABSTRACT FROM AUTHOR]

We assessed predicting final infarct size (using predischarge Selvester score) by 3 electrocardiographic variables in 267 patients with first anterior wall acute myocardial infarction (AMI) undergoing (n = 86) or not undergoing (n = 181) thrombolysis. Patients with previous AMI or inverted T waves in leads with ST elevation were excluded. The sum (sigma) of ST elevation, the number of leads with ST elevation, and the initial electrocardiographic pattern were determined on the admission electrocardiogram (absence (QRS-) or presence (QRS+) of distortion of the terminal portion of the QRS in > or =2 leads (J point > or =0.5 of the R-wave amplitude in leads I, aVL, V4 to V6, or presence of ST elevation without S waves in leads V1 to V3). There was no association between sigmaST elevation and final infarct size in patients who did or did not receive thrombolytic therapy. Analysis of covariance showed that the number of leads with ST elevation (F = 19.6), thrombolysis (F = 25.2), and QRS+ initial pattern (F = 19.5) were all associated with final infarct size (p <0.0001 for all). Among patients who did not receive thrombolytic therapy, the average Selvester score was 19.7+/-9.9 for the QRS- patients and 26.1+/-10.4 for the QRS+ patients (p = 0.02). Among patients who received thrombolytic therapy, the average Selvester score was 11.7+/-9.8 for the QRS- patients and 24.2+/-10.1 for the QRS+ patients (p <0.0001). Thrombolysis reduced final Selvester score only in the QRS- group (p <0.00001), but not in the QRS+ group (p = 0.45). It is concluded that (1) final Selvester score in anterior wall AMI can be predicted by the number of leads with ST elevation, the initial electrocardiographic pattern, and thrombolysis, and (2) thrombolysis reduces final Selvester score only in patients with QRS- pattern. [ABSTRACT FROM AUTHOR]