An Overview of Rhinoplasty Practices: European Academy of Facial Plastic Surgery, Collaborative Cross-Sectional Study.

This collaborative European Academy of Plastic Surgery (EAFPS) study aimed to provide an overview of rhinoplasty practices, informing clinician and patient decision making. It is a multicenter cross-sectional study, reported as per Strengthening the Reporting of Observational Studies in Epidemiology guidelines. All EAFPS members were contacted via email, inviting them to participate. Members expressing an interest to participate were asked to anonymously complete a questionnaire, related to rhinoplasties that they performed as first/supervising surgeon over a period from January 1, 2019 to January 1, 2022. A descriptive analysis was performed. One hundred and fifteen surgeons submitted data on 41,259 rhinoplasties from 33 countries. Eighty percent of rhinoplasties were primary, and 20% were secondary. Thirty five percent of primary rhinoplasties were closed and 65% were open. Thirty one percent of primary rhinoplasties were for cosmetic indications, 11% functional and 58% were for both. Of the 8147 secondary rhinoplasties, 44% were closed and 56% were open. Thirty percent were for cosmetic indications, 11% functional, and 59% for both cosmetic and functional. Ninety-one percent of rhinoplasties were performed by ENT surgeons, 3% by plastic surgeons, 5% by maxillofacial surgeons, and 1% were dual (maxillofacial and ENT) trained. One-thousand seven-hundred thirty primary rhinoplasties underwent revision surgery (5%) and 102 secondary rhinoplasties underwent revision surgery (1%). The most commonly reported indications for revision surgery were dorsal asymmetry, nasal blockage, and dissatisfaction with nasal tip. Three percent of rhinoplasties underwent preoperative psychological assessment. To the authors knowledge, this is the largest published rhinoplasty dataset. This study provides an overview of rhinoplasty practices that can be used for benchmarking and to guide clinician and patient decision making. Psychological assessment of prerhinoplasty appears insufficient with higher levels recommended to minimize unsuccessful outcomes. This study showcases the power of collaborative research and may serve as a catalyst for future collaborative facial plastic surgery research.

Bystander LECT2 amyloidosis in tumor nephrectomy.

Pathologic evaluation of the non-neoplastic renal parenchyma in tumor nephrectomy specimens is critical and can detect both renal-limited and systemic pathologies. We report the case of a 69-year-old Punjabi male who underwent cytoreductive nephrectomy for advanced renal cell carcinoma after immunotherapy. We detected clinically unexpected leukocyte chemotactic factor 2 (LECT2) amyloidosis during pathologic analysis of the surrounding non-neoplastic renal parenchyma, which was confirmed by mass spectrometry. LECT2 amyloidosis occurs predominantly in Hispanic patients and has only rarely been described in Punjabi patients. This case highlights the importance of careful pathologic evaluation of the non-neoplastic renal parenchyma of nephrectomy specimens and raises awareness that LECT2 amyloidosis can occur outside of the typical demographic of Hispanic patients.

1,2,3, MHC: a review of mass-spectrometry-based immunopeptidomics methods for relative and absolute quantification of pMHCs.

Quantitative mass-spectrometry-based methods to perform relative and absolute quantification of peptides in the immunopeptidome are growing in popularity as researchers aim to measure the dynamic nature of the peptide major histocompatibility complex repertoire and make copies-per-cell estimations of target antigens of interest. Multiple methods to carry out these experiments have been reported, each with unique advantages and limitations. This article describes existing methods and recent applications, offering guidance for improving quantitative accuracy and selecting an appropriate experimental set-up to maximize data quality and quantity.

Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Early relapse after autologous hematopoietic cell transplantation remains a poor prognostic factor in multiple myeloma but outcomes have improved over time.

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (<24 months), and to identify factors predicting for early vs late relapses (24-48 months post-AHCT). Over three periods (2001-2004, 2005-2008, 2009-2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35-38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky <90, stage III, >1 line of induction and lack of maintenance. Post-AHCT early relapse remains a poor prognostic factor, even though outcomes have improved over time.

A phase 1 trial of 90Y-Zevalin radioimmunotherapy with autologous stem cell transplant for multiple myeloma.

This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan (90Y-Zevalin) with high dose melphalan (HDM) therapy in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). In a 3+3 trial design, 30 patients received rituximab 250 mg/m2 with indium-111 ibritumomab tiuxetan (111In-Zevalin) for dosimetry (day -22); rituximab 250 mg/m2 with escalating doses of 90Y-Zevalin (day -14); melphalan 100 mg/m2 (days -2,-1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment. Each patient's 111In-Zevalin dosimetry data were used to calculate the dose of 90Y-Zevalin (in mCi) to deliver 10, 12, 14, 16, 18 or 20 Gy to the liver. Dose limiting toxicities were seen in 3 patients. The overall response rate was 73% (22/30) with stringent complete response in 2 patients; complete response, 5; very good partial response, 12; and partial response, 3. The median PFS was 16.5 months and the median overall survival was 63.4 months. In MM, the MTD of 90Y-Zevalin with HDM is 18 Gy to the liver. The addition of radiation with novel delivery methods such as radioimmunotherapy combined with standard transplant regimens warrants further study.

Autologous hematopoietic cell transplantation for multiple myeloma patients with renal insufficiency: a center for international blood and marrow transplant research analysis.

Autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients with renal insufficiency (RI) is controversial. Patients who underwent AHCT for MM between 2008 and 2013 were identified (N=1492) and grouped as normal/mild (⩾60 mL/min), N=1240, moderate (30-59), N=185 and severe RI (<30), N=67 based on Modification of Diet in Renal Disease. Multivariate analyses of non-relapse mortality (NRM), relapse, PFS and overall survival (OS) were performed. Of the 67 patients with severe RI, 35 were on dialysis prior to AHCT. Patients received melphalan 200 mg/m2 (Mel 200) in 92% (normal/mild), 75% (moderate) and 33% (severe) RI; remainder received 140 mg/m2 (Mel 140). Thirty four of 35 patients with severe RI achieved post-AHCT dialysis independence. The 5-year PFS for normal, moderate and severe RI was 35 (95% CI, 31-38)%, 40 (31-49)% and 27 (15-40)%, respectively, (P=0.42); 5-year OS for normal, moderate and severe RI was 68 (65-71)%, 68 (60-76)% and 60 (46-74)%, respectively, (P=0.69). With moderate RI, 5-year PFS for high-dose melphalan 140 mg/m2 was 18 (6-35)% and for Mel 200 was 46 (36-57)% (P=0.009). With severe RI, 5-year PFS Mel 140 was 25 (11-41) % and for Mel 200 was 32 (11-58)% (P=0.37). We conclude that AHCT is safe and effective in patients with MM with RI.

An individualised risk-adapted protocol of pre- and post transplant zoledronic acid reduces bone loss after allogeneic stem cell transplantation: results of a phase II prospective trial.

Bone loss occurs frequently following allogeneic haematopoietic stem cell transplantation (alloSCT). The Australasian Leukaemia and Lymphoma Group conducted a prospective phase II study of pretransplant zoledronic acid (ZA) and individualised post-transplant ZA to prevent bone loss in alloSCT recipients. Patients received ZA 4 mg before conditioning. Administration of post-transplant ZA from days 100 to 365 post alloSCT was determined by a risk-adapted algorithm based on serial bone density assessments and glucocorticoid exposure. Of 82 patients enrolled, 70 were alive and without relapse at day 100. A single pretransplant dose of ZA prevented femoral neck bone loss at day 100 compared with baseline (mean change -2.6±4.6%). Using the risk-adapted protocol, 42 patients received ZA between days 100 and 365 post alloSCT, and this minimised bone loss at day 365 compared with pretransplant levels (mean change -2.9±5.3%). Femoral neck bone loss was significantly reduced in ZA-treated patients compared with historical untreated controls at days 100 and 365. This study demonstrates that a single dose of ZA pre-alloSCT prevents femoral neck bone loss at day 100 post alloSCT, and that a risk-adapted algorithm is able to guide ZA administration from days 100 to 365 post transplant and minimise further bone loss.

Pediatric laryngeal carcinoma in a heterozygous carrier of Fanconi anemia.

A case of invasive, keratinizing squamous cell carcinoma of the larynx in an 8-year-old female treated with laryngectomy is presented. Perinatal exposure to human papilloma virus and constitutional heterozygosity for a FANCC mutation were identified, though FANCC heterozygosity is not known to be cancer predisposing. An additional tumor-associated mutation in NOTCH1 was also identified potentially contributing to oncogenesis. This case illustrates an exceedingly rare type of cancer in the pediatric population and discusses diagnostic workup, evaluation of risk factors for head and neck cancer, and treatment options.

DAS181 Treatment of Severe Parainfluenza Virus 3 Pneumonia in Allogeneic Hematopoietic Stem Cell Transplant Recipients Requiring Mechanical Ventilation.

Parainfluenza virus (PIV) may cause life-threatening pneumonia in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Currently, there are no proven effective therapies. We report the use of inhaled DAS181, a novel sialidase fusion protein, for treatment of PIV type 3 pneumonia in two allogeneic hematopoietic SCT recipients with respiratory failure.

Sperm abnormalities induced by pre-pubertal exposure to cyclophosphamide are effectively mitigated by Moringa oleifera leaf extract.

Moringa oleifera L. is a medicinal plant with potential antioxidant property. This study was aimed at investigating the chemoprotective effect of Moringa oleifera leaf extract (MOE) on cyclophosphamide (CP)-induced testicular toxicity. Two-week-old male Swiss albino mice were intraperitoneally injected with phosphate-buffered saline, 50 mg kg(-1) of CP and 25 mg kg(-1) of MOE. In combination treatment, mice were injected with 25 mg kg(-1) of MOE 24 h prior to CP injection, 24 h prior and post-CP injection and 24 h post-CP injection for 5 consecutive days (10 mg kg(-1) ). Six weeks later, mice were sacrificed to assess epididymal sperm parameters. MOE alone did not have any significant effect on sperm parameters. However, acute injection of CP resulted in significant decline in motility (P < 0.001), increase in head abnormality (P < 0.01) and DNA damage (P < 0.05). Combining MOE with CP increased the sperm density, motility and reduced head defect and DNA damage, irrespective of the schedule and dosage of MOE. Administration of MOE prior to CP significantly elevated the level of superoxide dismutase and catalase with concomitant decrease in lipid peroxidation in the testicular tissue. In conclusion, MOE may have potential benefit in reducing the loss of male gonadal function following chemotherapy.

Rehabilitation referrals and outcomes in the early period after hematopoietic cell transplantation.

In a cohort of inpatient hematopoietic cell transplantation (HCT) recipients, we assessed patterns of referral to rehabilitation treatment, functional performance and short-term outcomes in patients who received post-transplant rehabilitation in comparison with those who did not. Among 201 first-time HCT recipients, 53 (26%) were referred to an inpatient rehabilitation provider, had an assessment of functional performance using the Functional Independence Measure scale and underwent rehabilitation treatments to address functional needs. Patients who received rehabilitation therapy were more likely to be females (P=0.02), older than 60 years of age (P=0.0146), employed (P=0.01), have hypertension (P=0.02), peripheral vascular disease (P=0.01) and pre-transplant Karnofsky Performance Score (KPS) <90 (P=0.02). Mean functional performance scores for transfers and ambulation increased significantly in the group with rehabilitation interventions (P=0.0022 and P<0.0001, respectively). There was no difference between the groups that did and did not receive rehabilitation treatments in 30-day re-admission rates. Patients who are 60 years of age or older, with pre-transplant KPS<90, and pre-transplant hypertension were more likely to be referred for rehabilitation treatments in the early period after HCT. Future studies should be designed to determine the optimal timing and cost effectiveness of functional assessment and rehabilitation treatments in this high-risk population.

Facial transplantation: historical developments and future directions.

OBJECTIVE: To present the clinical outcomes obtained by the first facial transplant teams worldwide, reviewing current practice and addressing controversies. METHODS: A bibliographic search of Medline and Embase databases was performed, and a comparative analysis of all articles published from 1980 to the present was conducted. Two independent investigators screened the manuscripts in accordance with pre-defined criteria. RESULTS: A total of 12 partial and 5 full facial transplants were recorded in the literature. Procedures included partial and near-total facial myocutaneous flaps, and complex osteomyocutaneous grafts. Fifteen patients had fully vascularised grafts, and two patients died of transplant-related and infectious complications. CONCLUSION: Facial transplantation can restore quality of life and enable the social re-integration of recipients. Results published by the first facial transplant teams are promising. However, long-term reports of aesthetic and functional outcomes are needed to more precisely define outcomes. In addition, significant technical, medical and ethical issues remain to be solved.

Is 'informed consent' an 'understood consent' in hematopoietic cell transplantation?

Hematopoietic cell transplantation (HCT) is a complex and highly specialized medical treatment that is associated with significant risks, including death. Furthermore, transplantation is offered to patients who often have no other curative treatment alternatives. The routine-consent process for HCT typically occurs before HCT and is influenced by many factors related to patients, physicians and the transplant per se. These factors can impede the consent process and subsequently result in a failure of proper engagement in and an understanding of the procedure with resultant adverse consequences influencing patients and even the patient-physician relationship. We contend that informed consent is a dynamic and ongoing process and that better patient education can assist in the decision making, fulfill the ethical principle of respect for autonomy and engage the patient to maximize compliance and adherence to therapy. This manuscript reviews the key literature pertaining to the decision-making and consent process in HCT and proposes guidelines for improving the consent process. Strategies for improving patient comprehension, engagement and enhancing consent forms are discussed.