bluuebunny/crossref_metadata_2025 huggingface dataset:
Superiorly Based Posterior Pharyngeal Flaps
Authors: Butterfield James , Pencek Megan , Sweitzer Keith , Marrinan Eileen , Connolly Heidi , Neimanis Sara , Morrison Clinton
Published: April 2024

Background

Pharyngeal flap (PF) surgery is effective at improving velopharyngeal sufficiency, but historical literature shows a concerning prevalence rate of obstructive sleep apnea (OSA), reported as high as 20%. Our institution has developed a protocol to minimize risk of postoperative obstructive complications and increase safety of PF surgery. We hypothesize that (1) preoperative staged removal of significant adenotonsillar tissue along with (2) multiview videofluoroscopy to guide patient-specific surgical approach via appropriately sized PFs can result in excellent speech outcomes while limiting occurrence of OSA.

Methods

This was a retrospective chart review of all patients with velopharyngeal insufficiency (VPI) (aged 2–20 years) seen at the University of Rochester from 2015 to 2022 undergoing PF surgery to correct VPI. Nasopharyngoscopy was used for surgical planning and airway evaluation. Patients with tonsillar and adenoid hypertrophy underwent staged adenotonsillectomy at least 2 months before PF. Multiview videofluoroscopy was used to identify anatomic causes of VPI and to determine PF width. Patients underwent polysomnography and speech evaluation before and at least 6 months after PF surgery.

Results

Forty-one children aged 8.5 ± 4.1 years (range, 4 to 18 years) who underwent posterior PF surgery for VPI were identified. This included 10 patients with 22q11.2 deletion and 4 patients with Pierre Robin sequence. Thirty-nine patients had both pre- and postoperative speech data and underwent both a pre- and postoperative sleep study. Polysomnography showed no significant difference in obstructive apnea-hypopnea index after posterior PF surgery (obstructive apnea-hypopnea index preop, 1.3 ± 1.2 events per hour; postop, 1.7 ± 2.1 events per hour; P = 0.111). Significant improvements in speech outcome were seen in patients who underwent PF (modified Pittsburgh score preop, 11.52 ± 1.37; postop, 1.09 ± 2.35; P < 0.05).

Conclusions

Use of preoperative staged adenotonsillectomy as well as patient-specific PF dimensions results in effective resolution of VPI and a low risk of OSA.
Alternative Lymphatic Drainage Pathways in the Trunk Following Oncologic Therapy
Authors: Mehta Meeti , Sarrami Shayan , Moroni Elizabeth , Fishman Jordan , De La Cruz Carolyn
Published: April 2024

Background

Anatomic and functional descriptions of trunk and breast lymphedema following breast cancer treatment are emerging as indicators of lymphatic dysfunction. Indocyanine green-lymphangiography has been instrumental in characterizing this dysfunction in the extremity and can be applied to other regions. Previous work has established a validated Pittsburgh Trunk Lymphedema Staging System to characterize such affected areas. This study aims to identify risk and protective factors for the development of truncal and upper extremity lymphedema using alternative lymphatic drainage, providing implications for medical and surgical treatment.

Methods

Patients undergoing revisional breast surgery with suspicion of upper extremity lymphedema between 12/2014 and 3/2020 were offered lymphangiography. The breast and lateral/anterior trunks were visualized and blindly evaluated for axillary and inguinal lymphatic flow. A linear-weighted Cohen's kappa statistic was calculated comparing alternative drainage evaluation. Binomial regression was used to compute relative risks (RRs). Significance was assessed at alpha = 0.05.

Results

Eighty-six sides (46 patients) were included. Twelve sides underwent no treatment and were considered controls. Eighty-eight percent of the noncontrols had alternative lymphatic flow to the ipsilateral axillae (64%), ipsilateral groins (57%), contralateral axillae (20.3%), and contralateral groins (9.3%). Cohen's kappa for alternative drainage was 0.631 ± 0.043. Ipsilateral axillary and contralateral inguinal drainage were associated with reduced risk of developing truncal lymphedema [RR 0.78, confidence interval (CI) 0.63–0.97, P = 0.04; RR 0.32, CI 0.13–0.79, P = 0.01, respectively]. Radiation therapy increased risk of truncal and upper extremity lymphedema (RR 3.69, CI 0.96–14.15, P = 0.02; RR 1.92, CI 1.09–3.39, P = 0.03, respectively). Contralateral axillary drainage and axillary lymph node dissection were associated with increased risk of upper extremity lymphedema (RR 4.25, CI 1.09–16.61, P = 0.01; RR 2.83, CI 1.23–6.52, P = 0.01, respectively).

Conclusions

Building upon previous work, this study shows risk and protective factors for the development of truncal and upper extremity lymphedema. Most prevalent alternative channels drain to the ipsilateral axilla and groin. Ipsilateral axillary and contralateral inguinal drainage were associated with reduced risk of truncal lymphedema. Patients with radiation, axillary dissection, and contralateral axillary drainage were associated with increased risk of upper extremity lymphedema. These findings have important clinical implications for postoperative manual lymphatic drainage and for determining eligibility for lymphovenous bypass surgery.
Clinical and Histopathological Investigation of Pediatric Melanonychia
Authors: Ani Omar , Xu Wen , Chang Benjamin , Lin Ines C.
Published: April 2024

Hypothesis

The natural history of pediatric melanonychia and the necessity of biopsy for ruling out melanoma are debated in the literature. We hypothesize that there is a low rate of malignant nail pathology among pediatric patients undergoing nail bed biopsy for melanonychia.

Methods

We performed a retrospective chart review of 54 pediatric patients (age <18 years) at a single institution who presented with melanonychia and underwent nail bed biopsy from 2007 to 2022. Data points collected included patient demographics, medical history, physical exam findings, pathology reports, and clinical photos. Univariate and multivariate analyses were performed to assess for risk factors associated with high-risk pathology findings.

Results

The average age of melanonychia onset was 5.5 years (SD 4.4). The average age of first biopsy was 7.8 years (SD 4.3). On physical exam, 27 patients had at least four features concerning for melanoma (asymmetry, border irregularity, color heterogeneity, diameter > 1/3 of nail, evolving color, evolving diameter, Hutchinson's sign). The most common pathology diagnoses were melanocytic nevus (35%), atypical intraepidermal melanocytic proliferation (AIMP) with benign features (24%), subungual lentigo (22%), and AIMP with concerning features (17%). There were no cases of melanoma in situ or invasive malignant melanoma. On multivariate regression, the only significant risk factor associated with more concerning pathology (AIMP with concerning features) was the calendar year in which biopsy was performed (coefficient = −0.34, P = 0.016). There was no association between physical exam features and high-risk pathology. Twelve patients had surgical re-excision of the lesion, 6 of which were due to incomplete excision of AIMP with concerning features and 6 of which were due to recurrence.

Conclusions

Our case series did not find any cases of melanoma in situ or malignant melanoma arising from pediatric melanonychia. Atypical intraepidermal melanocytic proliferation with concerning features was associated only with the year in which the biopsy was performed, which may reflect the improved understanding of pediatric melanonychia as often benign despite concerning features on pathology. The decision to perform a nail matrix biopsy in pediatric melanonychia should be based on a collaborative discussion between the patient's parents, dermatologist, and plastic surgeon.
Lymphadenectomy After Melanoma—A National Analysis of Recurrence Rates and Risk of Lymphedema
Authors: Shen Chen , Shah Jennifer K. , Cevallos Priscila , Nazerali Rahim , Rosen Joseph M.
Published: April 2024

Introduction

Treatment for melanoma after a positive sentinel lymph node biopsy includes nodal observation or lymphadenectomy. Important considerations for management, however, involve balancing the risk of recurrence and the risk of lymphedema after lymphadenectomy.

Methods

From the Merative MarketScan Research Databases, adult patients were queried from 2007 to 2021. International Classification of Disease, Ninth (ICD-9) and Tenth (ICD-10) Editions, diagnosis codes and Current Procedural Terminology codes were used to identify patients with melanoma diagnoses who underwent an index melanoma excision with a positive sentinel lymph node biopsy (SLNB). Main outcomes were completion lymph node dissection (CLND) utilization after a positive SLNB, developing lymphedema with or without CLND, and nodal basin recurrence 3 months or more after index excision. Subanalyses stratified by index excision year (2007–2017 and 2018–2021) and propensity score matched were additionally conducted. Demographics and comorbidities (measured by Elixhauser index) were recorded.

Results

A total of 153,085,453 patients were identified. Of those, 359,298 had a diagnosis of melanoma, and 202,456 patients underwent an excision procedure. The study cohort comprised 3717 patients with a melanoma diagnosis who underwent an excision procedure and had a positive SLNB. The mean age of the study cohort was 49 years, 57% were male, 41% were geographically located in the South, and 24% had an Elixhauser index of 4+. Among the 350 patients who did not undergo CLND, 10% experienced recurrence and 22% developed lymphedema. A total of 3367 patients underwent CLND, of which 8% experienced recurrence and 20% developed lymphedema. Completion lymph node dissection did not significantly affect risk of recurrence [odds ratio (OR), 1.370, P = 0.090] or lymphedema (OR, 1.114, P = 0.438). After stratification and propensity score matching, odds of experiencing lymphedema (OR, 1.604, P = 0.058) and recurrence (OR, 1.825, P = 0.058) after CLND were not significantly affected. Rates of CLND had significantly decreased (P < 0.001) overtime, without change in recurrence rate (P = 0.063).

Conclusions

Electing for nodal observation does not increase the risk of recurrence or reduce risk of lymphedema. Just as CLND does not confer survival benefit, its decreased utilization has not increased recurrence rate.
Plastic Surgery Involvement With Surgical Management of Infected Ventricular Assist Devices Decreased Lifetime Return to Operating Room and 90-Day Infectious Complications
Authors: Sweitzer Keith , Fowler Cody , Butterfield James , Visca Adam , Mayorga-Young Danielle , Tomtschik Julia , Arias-Camison Raquel , Bell Derek
Published: April 2024

Background

The use of left ventricular assist devices (LVADs) for patients with end-stage cardiac failure awaiting heart transplantation has become increasingly common. However, ventricular assist device–related infections remain a major problem complicating their long-term use. Retrospective review has previously shown a decrease in lifetime return to operating room (RTOR) with no change in 90-day complications when a muscle or omental flap is used for coverage after washout for infection. We wished to determine if early plastic surgery intervention led to a decreased length of stay for these patients.

Methods

Patients with LVAD readmitted for LVAD infection at a single institution from 2008 to 2021 were identified using a preexisting database. Patients were followed retrospectively for an average of 3.2 years. Patient demographics, preoperative diagnosis/disease state, type of ventricular assist device inserted, postoperative day of ventricular assist device infection onset, definitive device coverage, timing of coverage procedure after the initial washout for infection, type of flap used for coverage, 90-day complications after definitive coverage, and lifetime return to operating room for infection were reviewed. Comparison analysis with χ
2 and analysis of variance testing was used to analyze outcomes.

Results

Of 568 patients admitted with an LVAD infection, 104 underwent operative debridement and closure by plastic and reconstructive surgery (PRS) or cardiothoracic surgery (CTS). Fifty-three underwent PRS closure, and 51 underwent CTS closure. There was an increased incidence of diabetes among the PRS group (P < 0.001); otherwise, there was no difference in baseline characteristics. There was increased RTOR over a lifetime with CTS closure compared with PRS (P = 0.03) and increased 90-day risk of infection (P = 0.007). Patients with PRS closure had an increased risk of postoperative hematoma (P = 046). Plastic and reconstructive surgery was typically consulted on hospital day 10. Both PRS and CTS closure patients were discharged on postoperative day 7, on average (P = 0.542).

Conclusions

Plastic surgery involvement with surgical decision making and closure of infected LVAD devices has a decrease in lifetime RTOR and decreased 90-day complications related to infections. There may be a benefit to earlier PRS consultation for coverage assessment.
The Evolving Plastic Surgery Applicant
Authors: Hemal Kshipra , Perez-Otero Sofia , Boyd Carter J. , Weichman Katie E. , Cohen Oriana D. , Thanik Vishal D. , Ceradini Daniel J.
Published: April 2024

Background

Plastic surgery training has undergone tremendous change and transitioned through many models over the years, including independent, combined, and integrated. This study evaluates how these changes and others have affected plastic surgery applicants' demographics and academic qualifications over the last 30 years.

Methods

Data on applicant demographics and academic qualifications were extracted from multiple sources including the National Resident Matching Program, the American Association of Medical Colleges, and cross-sectional surveys of plastic surgery applicants for the years 1992, 2005, 2011, and 2022. Data were compared using pairwise χ2 goodness of fit tests.

Results

The sex distribution of plastic surgery applicants changed significantly over the last 30 years: whereas men predominated in 1992 (86% male vs 14% female), by 2011, the distribution was nearly equal (54% male vs 46% female in both 2011 and 2022, P < 0.001).

The racial makeup of applicants also changed over time (P < 0.05). White applicants decreased from 73% in 1992 to 55% in 2011, and 53% in 2022. While there was an increase in Asian (7% to > 17% to > 20%) and other (13% to > 14% to > 21%) applicants over time, whereas the proportion of Black applicants remained stagnant (5% to > 6% to > 8%).

Applicants with prior general surgery experience declined precipitously over the years: 96% in 1992, 64% in 2005, 37% in 2011, and 26% in 2022 (P < 0.001). When compared with 1992, Alpha Omega Alpha status increased significantly in 2011 (36% vs 12%, P < 0.05) but did not change considerably in 2005 (22%) and 2022 (23%). Research experience increased dramatically over the years, with the proportion of applicants with at least one publication going from 43% in 1992, to 75% in 2005, to 89% in 2011, and to 99% in 2022 (P < 0.001). Applicant interest in academic plastic surgery did not change considerably over the years at roughly ranging from 30% to 50% of applicants (P = ns).

Conclusions

There has been a shift in the demographics and academic qualifications of plastic surgery applicants over the last 3 decades. Understanding this evolution is critical for reviewing and evaluating the makeup of our specialty, and enacting changes to increase representation where necessary.
Minimizing Nipple-Areolar Complex Complications in Prepectoral Breast Reconstruction After Nipple-Sparing Mastectomy
Authors: Perez-Otero Sofia , Hemal Kshipra , Boyd Carter J. , Kabir Raeesa , Sorenson Thomas J. , Jacobson Alexis , Thanik Vishal D. , Levine Jamie P. , Cohen Oriana D. , Karp Nolan S. , Choi Mihye
Published: April 2024

Purpose

Nipple-areolar complex (NAC) viability remains a significant concern following prepectoral tissue expander (TE) reconstruction after nipple-sparing mastectomy (NSM). This study assesses the impact of intraoperative TE fill on NAC necrosis and identifies strategies for mitigating this risk.

Methods

A chart review of all consecutive, prepectoral TEs placed immediately after NSM was performed between March 2017 and December 2022 at a single center. Demographics, mastectomy weight, intraoperative TE fill, and complications were extracted for all patients. Partial NAC necrosis was defined as any thickness of skin loss including part of the NAC, whereas total NAC necrosis was defined as full-thickness skin loss involving the entirety of the NAC. P < 0.05 was considered statistically significant.

Results

Forty-six patients (83 breasts) with an average follow-up of 22 months were included. Women were on average 46 years old, nonsmoker (98%), and nondiabetic (100%) and had a body mass index of 23 kg/m2. All reconstructions were performed immediately following prophylactic mastectomies in 49% and therapeutic mastectomies in 51% of cases. Three breasts (4%) were radiated, and 15 patients (33%) received chemotherapy. Mean mastectomy weight was 346 ± 274 g, median intraoperative TE fill was 150 ± 225 mL, and median final TE fill was 350 ± 170 mL. Partial NAC necrosis occurred in 7 breasts (8%), and there were zero instances of complete NAC necrosis. On univariate analysis, partial NAC necrosis was not associated with any patient demographic or operative characteristics, including intraoperative TE fill. In multivariable models controlling for age, body mass index, mastectomy weight, prior breast surgery, and intraoperative TE fill, partial NAC necrosis was associated with lower body mass index (odds ratio, 0.53; confidence interval [CI], 0.29–0.98; P < 0.05) and higher mastectomy weight (odds ratio, 1.1; CI, 1.01–1.20; P < 0.05). Prior breast surgery approached significance, as those breasts had a 19.4 times higher odds of partial NAC necrosis (95% CI, 0.88–427.6; P = 0.06).

Conclusions

Nipple-areolar complex necrosis following prepectoral TE reconstruction is a rare but serious complication. In this study of 83 breasts, 7 (8%) developed partial NAC necrosis, and all but one were able to be salvaged.
Is Tourniquet Pain the Result of Increased Compartment Pressure in the Forearm?
Authors: Manstein Carl Howard , Manstein Samuel Max , Manstein Ely
Published: April 2024

The pneumatic tourniquet has been a mainstay in upper extremity surgery by allowing the surgeon to operate in a blood-free field. Many upper extremity surgical procedures are done under local anesthesia or minimal sedation, and the problem of tourniquet pain is a vexing one. The question is posed: Is tourniquet pain the result of increased compartment pressure in the forearm? This study measured compartment pressures of the volar forearm in 10 healthy normotensive volunteers before inflation of a pneumatic tourniquet and compared it with pressure measurements taken while the tourniquet was still inflated after 15 minutes. Compartment pressures were measured using a Stryker needle manometer; all measurements were taken in the volar forearm by the senior author (C.H.M.). There was no increase in the volar/flexor compartment pressure of the forearm after 15 minutes of tourniquet inflation. All subjects complained of pain of the forearm, characteristically what is commonly called “tourniquet pain.” We therefore conclude that in the upper extremity, at least for relatively short operating times, appropriate inflation of a tourniquet does not induce the early onset of increased compartment pressure in the forearm.
Long-term Survival and Functional Outcomes of Laparoscopic Surgery for Clinical Stage I Ultra-low Rectal Cancers Located Within 5 cm of the Anal Verge
Authors: Ito Masaaki , Tsukada Yuichiro , Watanabe Jun , Fukunaga Yosuke , Hirano Yasumitsu , Sakamoto Kazuhiro , Hamamoto Hiroki , Yoshimitsu Masanori , Horie Hisanaga , Matsuhashi Nobuhisa , Kuriu Yoshiaki , Nagai Shuntaro , Hamada Madoka , Yoshioka Shinichi , Ohnuma Shinobu , Hayama Tamuro , Otsuka Koki , Inoue Yusuke , Ueda Kazuki , Toiyama Yuji , Maruyama Satoshi , Yamaguchi Shigeki , Tanaka Keitaro , Suzuki Motoko , Naitoh Takeshi , Ando Koji , Watanabe Masahiko ,   for the Ultimate Trial Group
Published: April 2024

Objective:

To clarify the long-term oncological outcomes and postoperative anal, urinary, and sexual functions after laparoscopic surgery for clinical stage I very low rectal carcinoma located near the anal canal.

Background:

Laparoscopic surgery is widely applied for rectal cancer; however, concerns remain, with some studies showing poorer outcomes compared with open surgery.

Methods:

This single-arm, phase II trial included patients registered preoperatively from 47 institutions in Japan. The planned sample size was 300. The primary end point was the 3-year local recurrence rate. Anal, urinary, and sexual functions were evaluated using a prospective questionnaire.

Results:

Three hundred patients were registered between January 2014 and March 2017. Anus-preserving surgery was performed in 278 (93%), including 172 who underwent intersphincteric resection (58%) and 106 (36%) who underwent low anterior resection. The 3-year cumulative local recurrence rate was 6.3%. At 3 years postoperatively, 87% of patients used their own anus, and the median incontinence score improved from 12 at 3 months to 8 at 3 years. Only 5% of patients had severe incontinence (incontinence score of 16 points). Postoperative urinary function evaluation showed that the International Prostate Symptom Score and Overactive Bladder Symptom Score decreased 1 week after surgery but recovered to preoperative level 1 month after surgery. International Consultation on Incontinence Questionnaire-Sort Form remained almost stable after surgery. Sexual function evaluation using the International Index of Erectile Function-5 and International Index of Erectile Function-15 revealed that the patients had deteriorated 3 months after surgery but had recovered only slightly by 6 months.

Conclusions:

Laparoscopic surgery achieves feasible long-term oncological outcomes and a high rate of anus preservation with moderate anal function and an acceptable incontinence score. While urinary function recovered rapidly, sexual function showed poor recovery.
A Primary Report 166 Cases of Abdominal or Pelvic Neuroblastoma Surgery Utilizing the International Neuroblastoma Surgical Report Form (INSRF)
Authors: Chang Saishuo , Yang Shen , Yu Tong , Zhang Qi , Lin Yu , Ren Qinghua , Cheng Haiyan , Chang Xiaofeng , Zhu Zhiyun , Cai Siyu , Feng Jun , Han Jianyu , Yang Wei , Qin Hong , Wang Huanmin
Published: April 2024

Background and aims:

Surgery is pivotal in the management of neuroblastoma (NB), particularly in patients with Image-Defined Risk Factors (IDRFs). The International Neuroblastoma Surgical Report Form (INSRF) was introduced to enhance surgical reporting quality and analyze the defining role of extensive surgery in NB. This study reports our experience with INSRF and explores new criteria for evaluating the extent of surgical resection.

Methods:

INSRF was deployed to critically analyze 166 patients with abdominal or pelvic NB who underwent surgery at our department between October 2021 and June 2023. Patient demographics, clinical characteristics, surgical datasets, and postoperative complications were described in detail. Receiver operating characteristic (ROC) curves were used to explore a new method to evaluate the extent of resection. A questionnaire was formulated to obtain attitudes/feedback and commentary from surgical oncologists with INSRF.

Results:

166 neuroblastoma patients with a median disease age 36.50 months. This study collated 320 INSRF reports. Among the 166 index cases, 137 were documented by two surgeons, with a concordance rate of 16.78%. Items with high inconsistency were (i) the extent of tumor resection (29.20%), (ii) renal vein involvement (25.55%), (iii) abdominal aorta encasement (16.79%), and (iv) mesenteric infiltration (17.52%). According to INSRF, the extent of resection was complete excision in 86 (51.81%) patients, minimal residual tumor < 5 cm3 in 67 (40.36%) patients, and incomplete excision > 5 cm3 in 13 (7.83%) patients. In ROC curve analysis, the number of vessels encased by tumors > 3 had a high predictive value in determining that a tumor could not be completely resected (AUC 0.916, sensitivity 0.838, specificity 0.826) using INSRF as the gold standard reference. The questionnaires showed that surgeons agreed that the extent of resection and tumor involvement of organ/vascular structures were important, while the definition and intervention(s) of intraoperative complications were less operational and understandable.

Conclusions:

INSRF has significant clinical application in neuroblastoma surgery. The extent of resection can be predicted based on the number of tumor-encased blood vessels. Supplementary information should be considered with the INSRF to aid practitioner reporting. Multicenter studies are needed to explore the defining role of INSRF in NB surgical management.
Tissue-resident Lymphocytes Are Released During Hypothermic and Normothermic Machine Perfusion of Human Donor Kidneys
Authors: Hullegie-Peelen Daphne M. , Hesselink Dennis A. , Dieterich Marjolein , Minnee Robert C. , Peeters Annemiek , Hoogduijn Martin J. , Baan Carla C.
Published: April 2024

Background.

Machine perfusion is the preferred preservation method for deceased donor kidneys. Perfusate fluid, which contains a complex mixture of components, offers potential insight into the organ’s viability and function. This study explored immune cell release, particularly tissue-resident lymphocytes (TRLs), during donor kidney machine perfusion and its correlation with injury markers.

Methods.

Perfusate samples from hypothermic machine perfusion (HMP; n = 26) and normothermic machine perfusion (NMP; n = 16) of human donor kidneys were analyzed for TRLs using flow cytometry. Residency was defined by expressions of CD69, CD103, and CD49as. TRL release was quantified exclusively in NMP. Additionally, levels of cell-free DNA, neutrophil gelatinase-associated lipocalin, and soluble E-cadherin (sE-cadherin) were measured in NMP supernatants with quantitative polymerase chain reaction and enzyme-linked immunosorbent assay.

Results.

Both HMP and NMP samples contained a heterogeneous population of TRLs, including CD4+ tissue-resident memory T cells, CD8+ tissue-resident memory T cells, tissue-resident natural killer cells, tissue-resident natural killer T cells, and helper-like innate lymphoid cells. Median TRL proportions among total CD45+ lymphocytes were 0.89% (NMP) and 0.84% (HMP). TRL quantities in NMP did not correlate with donor characteristics, perfusion parameters, posttransplant outcomes, or cell-free DNA and neutrophil gelatinase-associated lipocalin concentrations. However, CD103+ TRL release positively correlated with the release of sE-cadherin, the ligand for the CD103 integrin.

Conclusions.

Human donor kidneys release TRLs during both HMP and NMP. The release of CD103+ TRLs was associated with the loss of their ligand sE-cadherin but not with general transplant injury biomarkers.
Exception Policy Change Increased the Simultaneous Kidney-liver Transplant Probability of Polycystic Disease in the Centers With High Median MELD at Transplantation
Authors: Miyake Katsunori , Kim Dean Y. , Chau Lucy C. , Trudeau Sheri , Kitajima Toshihiro , Wickramaratne Niluka , Shimada Shingo , Nassar Ahmed , Yoshida Atsushi , Abouljoud Marwan S. , Nagai Shunji
Published: March 2024

Background.

In 2019, Organ Procurement and Transplantation Network/United Network for Organ Sharing changed the exception policy for liver allocation to the median model for end-stage liver disease at transplantation (MMaT). This study evaluated the effects of this change on-waitlist outcomes of simultaneous liver-kidney transplantation (SLKT) for patients with polycystic liver-kidney disease (PLKD).

Methods.

Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry, 317 patients with PLKD listed for SLKT between January 2016 and December 2021 were evaluated. Waitlist outcomes were compared between prepolicy (Era 1) and postpolicy (Era 2) eras.

Results.

One-year transplant probability was significantly higher in Era 2 than in Era 1 (55.7% versus 37.9%; P = 0.001), and the positive effect on transplant probability of Era 2 was significant after risk adjustment (adjusted hazard ratio, 1.76; 95% confidence interval, 1.22-2.54; P = 0.002 [ref. Era 1]), whereas waitlist mortality was comparable. Transplant centers were separated into the high and low MMaT groups with a score of 29 (median MMaT) and transplant probability in each group between eras was compared. In the high MMaT transplant centers, the 1-y transplant probability was significantly higher in Era 2 (27.5% versus 52.4%; P = 0.003). The positive effect remained significant in the high MMaT center group (adjusted hazard ratio, 2.79; 95% confidence interval, 1.43-5.46; P = 0.003 [ref. Era 1]) but not in the low MMaT center group. Although there was a difference between center groups in Era 1 (P = 0.006), it became comparable in Era 2 (P = 0.54).

Conclusions.

The new policy increased 1-y SLKT probability in patients with PKLD and successfully reduced the disparities based on center location.
Normothermic Liver Machine Perfusion and Successful Transplantation of Split Liver Grafts: From Proof of Concept to Clinical Implementation
Authors: Krendl Felix J. , Cardini Benno , Laimer Gregor , Singh Jessica , Resch Thomas , Oberhuber Rupert , Schneeberger Stefan
Published: March 2024

Background.

Normothermic liver machine perfusion (NLMP) is advancing the field of liver transplantation (LT). Beyond improved preservation and organ assessment, NLMP helps to increase organ utilization. We herein address the feasibility and merit of NLMP in split liver transplantation (SLT) to postpone the transplantation of the second split graft to the following day.

Methods.

We analyzed the perfusion characteristics and outcomes of all consecutive adult recipients who underwent SLT following NLMP from February 1, 2018, to June 30, 2023. The primary endpoint was 90-d graft and patient survival. Secondary endpoints were posttransplant complications and 90-d morbidity.

Results.

Three right and 3 extended right SLT following NLMP have been performed. NLMP was uneventful in all cases. Perfusion characteristics differed according to graft volume. Mean perfusion time was 17:00 h (±05:13) and bile production ranged between 8 and 21 mL/h. All split grafts fulfilled predefined center viability criteria during NLMP and were transplanted on the following day. The 90-d graft and patient survival rate was 100%. Three patients (50%) required an early relaparotomy, and 2 patients (33.3%) developed biliary complications. The 90-d morbidity as recorded by the comprehensive complication index was 62.7 (±24.7).

Conclusion.

NLMP of split liver grafts is technically feasible and safe. Through prolongation of preservation time, NLMP allows to safely postpone transplantation of the second split liver graft to the next day.
Nonadjacent Dependencies and Syntactic Structure of Chimpanzee Action During a Natural Tool-Use Task
Authors: Howard-Spink Elliot , Hayashi Misato , Matsuzawa Tetsuro , Schofield Daniel , Gruber Thibaud , Biro Dora
Published: March 2024

The hierarchical organization of sequential behaviour, and the ability to compensate for nonadjacent sequential dependencies, are fundamental and interrelated abilities supporting complex human behaviours, including language and tool use. To understand how the cognition underlying these structural properties of human behaviour evolved, we can gain valuable insight from studying the sequential behaviours of nonhuman animals. Among the behaviours of nonhuman apes, tool use has been hypothesised to be a domain of behaviour which likely involves hierarchical organization. However thus far, evidence supporting this hypothesis comes from methodologies which have been criticised in their objectivity. Additionally, the extent to which nonadjacent dependencies appear in primate action sequences during tool use has not been formally investigated. We used estimations of mutual information (MI, a measure of dependency strength between sequence elements) to evaluate both the extent to which wild chimpanzees produce nonadjacent dependencies during a naturalistic tool use task (nut cracking), as well as how sequences of actions are organized during tool use. Half of adult chimpanzees produce nonadjacent dependencies at significantly greater sequential distances than comparable, nonhierarchical Markov models, including when repeated actions had been accounted for. Additionally, for the majority of chimpanzees, MI decay with increasing sequential distance included a power law relationship, which is a key indicator that most chimpanzees draw upon forms of hierarchical structuring when organizing behaviours during tool use. Our analysis offered the greatest support for a system of organization which involved the production of short subroutines of actions (2 to 8 actions), which are hierarchically arranged into sequences, and is consistent with previous qualitative descriptions of ape tool-use behaviours. Interindividual variability was detected within our analysis in both the distance dependencies were detected, and the most likely structuring mechanism for sequential action organization. We discuss these results in light of possible interindividual variation, in addition to methodological considerations for applications of MI estimations to sequential behaviours. Moreover, we discuss our main findings alongside hypotheses for the coevolution of complex syntax in language and tool action across hominin evolutionary history.
Metatranscriptomics-based metabolic modeling of patient-specific urinary microbiome during infection
Authors: Josephs-Spaulding Jonathan , Rettig Hannah Clara , Zimmermann Johannes , Chkonia Mariam , Mischnik Alexander , Franzenburg Sören , Graspeuntner Simon , Rupp Jan , Kaleta Christoph
Published: March 2024

Urinary tract infections (UTIs) are a major health concern which incur significant socioeconomic costs in addition to substantial antibiotic prescriptions, thereby accelerating the emergence of antibiotic resistance. To address the challenge of antibiotic-resistant UTIs, our systems biology approach uncovers patient-specific uromicrobiome insights that are focused on community utilization of metabolites. By leveraging the distinct metabolic traits of patient-specific pathogens, we aim to identify metabolic dependencies of pathogens and provide suggestions for targeted interventions for future studies. Combining patient-specific metatranscriptomic data with genome-scale metabolic modeling and data from the Human Urine Metabolome, this study explores UTIs from a systems biology perspective through the reconstruction of tailored microbial community models to mirror the metabolic profiles of individual UTI patients’ urinary microbiomes. Delving into patient-specific bacterial gene expressions and microbial interactions, we identify metabolic signatures and propose mechanisms for UTI pathology. Our research underscores the potential of integrating metatranscriptomic data using systems biological approaches, providing insights into disease metabolic mechanisms and potential phenotypic manifestations. This contribution introduces a new method that could guide treatment options for antibiotic-resistant UTIs, aiming to lessen antibiotic use by combining the pathogens’ unique metabolic traits.

Abstract Figure

Graphical Abstract

Metatranscriptome sequencing was used to investigate the functional uromicrobiome across a cohort of 19 individuals; patient-specific microbiome community models were reconstructed and simulated in a virtual urine environment. Total RNA was extracted from patients’ urine and sequenced to assess the metatranscriptome, providing insights into patient-specific uromicrobiome microbial taxa and their associated gene expression during urinary tract infections (UTIs). These combinatory datasets derived from metatranscriptomics data were further expanded first to reconstruct species specific metabolic models that were conditioned with gene expression. Gene expression conditioned metabolic models were combined in an in silico environment with a defined urine media to construct patient-specific context-specific uromicrobiome models, enabling an understanding of each patient’s unique microbiome. Using this approach, we aimed to identify patient-specific microbiome dynamics and provide insight towards various metabolic features that can be utilized or validated in future studies for individualized intervention strategies. Created withwww.biorender.com.
IT IS NOT A SMALL WORLD FOR PSYCHIATRIC PATIENTS: Small-world of psychiatric patients
Authors: Akın Ata , Yorgancıgil Emre , Öztürk Ozan Cem , Sütçübaşı Bernis , Kırımlı Ceyhun , Kırımlı Elçim , Dumlu Seda Nilgün , Yükselen Gülnaz , Erdoğan S. Burcu
Published: March 2024

Individuals suffering from Obsessive Compulsive Disorder (OCD) and Schizophrenia (SCZ) frequently exhibit symptoms of cognitive disassociations, which are linked to poor functional integration among brain regions. The loss of integration can be assessed using graph metrics computed from functional connectivity matrices (FCMs) derived from neuroimaging data. A healthy brain with an effective connectivity pattern exhibits small-world features with high clustering coefficients and shorter path lengths in contrast to random networks. We analyzed neuroimaging data from 60 subjects (13healthy controls, 21 OCD and 26 SCZ) using functional near-infrared spectroscopy (fNIRS) during a color word matching Stroop Task and computed FCMs. Small-world features were evaluated using the Global Efficiency (GE), Clustering Coefficient (CC), Modularity (Q), and small-world parameter (σ). The proposed pipeline in this study for fNIRS data processing demonstrates that patients with OCD and SCZ exhibit small-world features resembling random networks, as indicated by higherGEand lowerCCvalues compared to healthy controls, implying a higher operational cost for these patients.

AUTHOR SUMMARY

Individuals suffering from Obsessive Compulsive Disorder (OCD) and Schizophrenia (SCZ) frequently exhibit symptoms of cognitive disassociations, which are linked to poor functional integration among brain regions. The loss of integration can be assessed using graph metrics computed from functional connectivity matrices (FCMs) derived from neuroimaging data. A healthy brain with an effective connectivity pattern exhibits small-world features with high clustering coefficients and shorter path lengths in contrast to random networks. We analyzed neuroimaging data from 60 subjects (13healthy controls, 21 OCD and 26 SCZ) using functional near-infrared spectroscopy (fNIRS) during a color word matching Stroop Task and computed FCMs. Small-world features were evaluated using the Global Efficiency (GE), Clustering Coefficient (CC), Modularity (Q), and small-world parameter (σ). The proposed pipeline in this study for fNIRS data processing demonstrates that patients with OCD and SCZ exhibit small-world features resembling random networks, as indicated by higherGEand lowerCCvalues compared to healthy controls, implying a higher operational cost for these patients.
Simple shell measurements do not consistently predict habitat in turtles: a reply to Lichtig and Lucas (2017)
Authors: Evers Serjoscha W. , Foth Christian , Joyce Walter G. , Hermanson Guilherme
Published: March 2024

Inferring palaeoecology for fossils is a key interest of palaeobiology. For groups with extant representatives, correlations of aspects of body shape with ecology can provide important insights to understanding extinct members of lineages. The origin and ancestral ecology of turtles is debated and various shell or limb pro-portions have been reported to correlate with habitat ecology among extant turtles, such that they may be informative for inferring the ecology of fossil turtles, including early shelled stem turtles. One recently described method proposes that simple shell measurements that effectively quantify shell doming and plastron width can differentiate habitat classes among extant turtles in linear discriminant analysis, whereby aquatic turtles have low domed shells with narrow plastra. The respective study proposes unorthodox habitat predictions for key fossil turtles, including aquatic lifestyles for the early turtleProganochelys quenstedtiiand the meiolaniformMeiolania platyceps, and terrestrial habits for the early turtleProterochersis robusta. Here, we show that these published results are the consequence of questionable methodological choices such as omission of species data which do not conform to a preconceived shell shape-ecology association. When these choices are reversed, species measurements for fossils are corrected, and phylogenetic flexible discriminant analysis applied, habitat cannot be correctly predicted for extant turtles based on these simple shell measurements. This invalidates the method as well as the proposed palaeohabitats for fossils.
Spinal motoneuron excitability is homeostatically-regulated through β-adrenergic neuromodulation in wild-type and presymptomatic SOD1 mice
Authors: Antonucci Stefano , Caron Guillaume , Dikwella Natalie , Krishnamurty Sruthi Sankari , Harster Anthony , Zarrin Hina , Tahanis Aboud , Heuvel Florian olde , Danner Simon M. , Ludolph Albert C. , Grycz Kamil , Bączyk Marcin , Zytnicki Daniel , Roselli Francesco
Published: March 2024

Homeostatic feedback loops are essential to stabilize the activity of neurons and neuronal networks. It has been hypothesized that, in the context of Amyotrophic Lateral Sclerosis (ALS), an excessive gain in feedback loops might hyper- or hypo-excite motoneurons (MNs) and contribute to the pathogenesis. Here, we investigated how the neuromodulation of MN intrinsic properties is homeostatically controlled in presymptomatic adult SOD1(G93A) mice and in the age-matched control WT mice. First, we determined that β2 and β3-adrenergic receptors, which are Gs-coupled receptors and subject to tight and robust feedback loops, are specifically expressed in spinal MNs of both SOD1 and WT mice at P45. We then demonstrated that these receptors elicit a so-far overlooked neuromodulation of the firing and excitability properties of MNs. These electrical properties are homeostatically regulated following receptor engagement, which triggers ion channel transcriptional changes and downregulates those receptors. These homeostatic feedbacks are not dysregulated in presymptomatic SOD1 mice, and they set the MN excitability upon β-adrenergic neuromodulation.
Associations between parenting and cognitive and language abilities at age 2 depend on prenatal exposure to disadvantage
Authors: Leverett Shelby D. , Brady Rebecca G. , Tooley Ursula A. , Lean Rachel E. , Tillman Rebecca , Wilson Jillian , Ruscitti Michayla , Triplett Regina L. , Alexopoulos Dimitrios , Gerstein Emily D. , Smyser Tara A. , Warner Barbara , Luby Joan L. , Smyser Christopher D. , Rogers Cynthia E. , Barch Deanna M.
Published: March 2024

Objective

To investigate whether parenting and/or neonatal brain volumes mediate the associations between prenatal social disadvantage (PSD) and cognitive/language abilities; and whether these mechanisms vary by level of disadvantage.

Study Design

Pregnant women were recruited from obstetric clinics in St Louis, Missouri. PSD encompassed access to social (e.g., education) and material (e.g., income-to-needs, health insurance, area deprivation, and nutrition) resources during pregnancy. Neonates underwent brain magnetic resonance imaging. Mother-child dyads (N=202) returned at age 1 for parenting measures and at age 2 for cognition/language assessments (Bayley-III). Generalized additive and mediation models tested hypotheses.

Results

Greater PSD was nonlinearly associated with poorer cognitive/language scores. The relation between parenting and cognition/language was moderated by PSD, such that supportive and non-supportive parenting behaviors only related to cognition/language in children with low PSD. Further, parenting mediations differed by level of PSD, such that both supportive and non-supportive parenting mediated PSD-cognition/language associations in children with low PSD, but not in children with high PSD. PSD-associated reductions in neonatal subcortical grey matter (β=.19,q=.03), white matter (β=.23,q=.02), and total brain volume (β=.18,q=.03) were associated with lower cognition, but they did not mediate PSD-cognition associations.

Conclusions

Parenting moderates and mediates associations between PSD and early cognitive and language development, but only in families with lower levels of social disadvantage. These findings, while correlational, suggest that there may be a critical threshold of disadvantage, below which mediating or moderating factors become less effective, highlighting the importance of reducing disadvantage as primary prevention.
Expert Navigators Deploy Rational Complexity-Based Decision Precaching for Large-Scale Real-World Planning
Authors: Fernandez Velasco Pablo , Griesbauer Eva-Maria , Brunec Iva , Morley Jeremy , Manley Ed , McNamee Daniel C. , Spiers Hugo J.
Published: March 2024

Efficient planning is a distinctive hallmark of intelligence in humans, who routinely make rapid inferences over complex world contexts. However, studies investigating how humans accomplish this tend to focus on naive participants engaged in simplistic tasks with small state-spaces, which do not reflect the intricacy, ecological validity, and human specialisation in real-world planning. In this study, we examine the street-by-street route planning of London taxi drivers navigating across more than 26,000 streets in London (UK). We explore how planning unfolded dynamically over different phases of journey construction and identify theoretic principles by which these expert human planners rationally precache decisions at prioritised environment states in an early phase of the planning process. In particular, we find that measures of path complexity predict human mental sampling prioritisation dynamics independent of alternative measures derived from the real spatial context being navigated. Our data provide real-world evidence for complexity-driven remote state access within internal models and precaching during human expert route planning in very large structured spaces.

Significance statement

Humans can plan efficiently in incredibly complex situations. Existing work has looked at naive participants in simple tasks, which might not be representative of how experts plan in the real world. Here, we study the real-world planning process of London taxi drivers – famous for their expert knowledge of London. By analyzing their response times as a proxy for thinking times, we reveal that at an early stage in their thought process, they store decisions at key street junctions to keep them in mind for later planning. Using computational modeling, we show that taxi drivers prioritize inference at street junctions according to normative metrics measuring how critical a particular decision is for reducing the complexity of planning across the entire city.