Medical Journal Websites Include Online-Only Content Plus Intriguing and Unique Features

Arthroscopy; Arthroscopy Techniques; and Arthroscopy, Sports Medicine, and Rehabilitation (ASMAR) websites include content that is available only online. Every time we visit the websites, we discover new content and educational features worth exploring. From meeting abstracts to multimedia, and from research pearls collections to world maps indicating the reach of our journals, a tour of our websites is enthralling. You can even take a bite of a hamburger.     

Cutaneous mucormycosis infection by absidia in two consecutive liver transplant patients

Mucormycosis, although an infrequent fungal infection, has a high mortality in patients undergoing orthotopic liver transplantation. We present two cases of cutaneous Absidia mucormycosis in two successive patients undergoing liver transplantation in our hospital. In our literature search, we encountered only one published case of Absidia infection in liver transplantation.     

Arthroscopy Honors Award-Winning Articles and Authors: Our Annual Research Awards

With genuine gratitude to the AANA Education Foundation for their unstinting support, it is our honor to announce Arthroscopy’s Annual Awards for the best Clinical Research, Basic Science Research, Resident/Fellow Research, and Systematic Reviews published in 2022, as well as the Most Downloaded and Most Cited papers published 5 years ago. And as is customary in January, our editors update their disclosures of potential conflicts of interest, as we require of authors, and we update our masthead to introduce new members of our Editorial Board and Social Media Board.     

The world’s ten most feared fungi

An account is provided of the world’s ten most feared fungi. Within areas of interest, we have organized the entries in the order of concern. We put four human pathogens first as this is of concern to most people. This is followed by fungi producing mycotoxins that are highly harmful for humans; Aspergillus flavus, the main producer of aflatoxins, was used as an example. Problems due to indoor air fungi may also directly affect our health and we use Stachybotrys chartarum as an example. Not everyone collects and eats edible mushrooms. However, fatalities caused by mushroom intoxications often make news headlines and therefore we include one of the most poisonous of all mushrooms, Amanita phalloides, as an example. We then move on to the fungi that damage our dwellings causing serious anxiety by rotting our timber structures and flooring. Serpula lacrymans, which causes dry rot is an excellent example. The next example serves to represent all plant and forest pathogens. Here we chose Austropuccinia psidii as it is causing devastating effects in Australia and will probably do likewise in New Zealand. Finally, we chose an important amphibian pathogen which is causing serious declines in the numbers of frogs and other amphibians worldwide. Although we target the top ten most feared fungi, numerous others are causing serious concern to human health, plant production, forestry, other animals and our factories and dwellings. By highlighting ten feared fungi as an example, we aim to promote public awareness of the cost and importance of fungi.     

Misinterpretation of P Values and Statistical Power Creates a False Sense of Certainty: Statistical Significance,Lack of Significance,and the Uncertainty Challenge

Despite great advances in our understanding of statistics, a focus on statistical significance and P values, or lack of significance and power, persists. Unfortunately, this dichotomizes research findings comparing differences between groups or treatments as either significant or not significant. This creates a false and incorrect sense of certainty. Statistics provide us a measure of the degree of uncertainty or random error in our data. To improve the way in which we communicate and understand our results, we must include in reporting a probability, or estimate, of our degree of certainty (or uncertainty). This will allow us to better determine the risks and benefits of a treatment or intervention. Approaches that allow us to estimate, account for, and report our degree of uncertainty include use of confidence intervals, P-value functions, and Bayesian inference (which incorporates prior knowledge in our analysis of new research data). Surprise values (S values, which convert P values to the number of successive identical results of flips of a fair coin) express outcomes in an intuitive manner less susceptible to dichotomizing results as significant or not significant. In the future, researchers may report P values (if they wish) but could go further and provide a confidence interval, draw a P-value function graph, or run a Bayesian analysis. Authors could calculate and report an S value. It is insufficient to mindlessly report results as significant versus not significant without providing a quantitative estimate of the uncertainty of the data.     

The Doctor Is In! Diagnostic Analysis

To make meaningful inferences based on our regression models, we must ensure that we have met the necessary assumptions of these tests. In this commentary, we review these assumptions and those for the t-test and analysis of variance, and introduce a variety of methods, formal and informal, numeric and visual, for assessing conformity with the assumptions.     

Donor and recipient gender distribution in a Saudi kidney transplant center

Worldwide reports from national renal registries show a donor gender imbalance in living renal transplantation. In these studies women represent on the one hand about 65% of living donors and on the other hand, receive fewer kidneys than men. Because of scarcity of reports on this matter from the Eastern world, we undertook this study to assess the gender demographics of recipients and living donors in our transplant center in the eastern region of Saudi Arabia. We retrospectively reviewed our living related transplantations performed from 1992 to 2008 (n = 135). Ninety-one males (67.4%) versus 44 females (32.6%) donated a kidney (P = .0000.) The male predominance (n = 80; 59.3%) was also noticed among recipients with 80 versus 55 females (40.7%; P = .001). When splitting the results into two periods, 1992 to 1999 versus 2000 to 2008, we noticed a trend to an improved donation rate from females, rising from 29% to 38.7% (P = NS). Further analysis showed that brothers were giving more frequently to brothers than to sisters (38 vs 11; P < .001) and that sisters donated equally to brothers and sisters (12 vs 11; P = NS). Interspousal donation showed no significant difference between husband to wife and vice versa (4 vs 5). Unlike the international experience, our study showed men to be donating more kidneys than women. Sociocultural reasons may have a role in such findings.     

Auld Lang Syne: A New Year Brings Awards and a New Cover

“Auld Lang Syne,” a traditional poem used to welcome the New Year, asks rhetorically, “Should old acquaintance be forgot, and never brought to mind?” At Arthroscopy, the answer is a resounding no. We view January as an opportunity to celebrate the abundance and excellence of research published in Arthroscopy. This year, we have decided to spread our applause, approval, and appreciation to recognize both award winners and runners-up, whose distinction in research epitomizes the bounty that is Arthroscopy. In addition, we proudly introduce a new cover.     

Identification of novel regulators of osteoblast matrix mineralization by time series transcriptional profiling

Bone mineralization is a carefully orchestrated process, regulated by a number of promoters and inhibitors that function to ensure effective hydroxyapatite formation. Here we sought to identify new regulators of this process through a time series microarray analysis of mineralising primary osteoblast cultures over a 27 day culture period. To our knowledge this is the first microarray study investigating murine calvarial osteoblasts cultured under conditions that permit both physiological extracellular matrix mineralization through the formation of discrete nodules and the terminal differentiation of osteoblasts into osteocytes. RT-qPCR was used to validate and expand the microarray findings. We demonstrate the significant up-regulation of >6,000 genes during the osteoblast mineralization process, the highest-ranked differentially expressed genes of which were those dominated by members of the PPAR-γ signalling pathway, namely Adipoq, Cd36 and Fabp4. Furthermore, we show that the inhibition of this signalling pathway promotes matrix mineralisation in these primary osteoblast cultures. We also identify Cilp, Phex, Trb3, Sox11, and Psat1 as novel regulators of matrix mineralization. Further studies examining the precise function of the identified genes and their interactions will advance our understanding of the mechanisms underpinning biomineralization.     

Consequences of partial duplications of the human CFTR gene on cf diagnosis: Mutations or ectopic variations

CFTR exon 10 and its flanking regions are duplicated in the human genome. These duplications present mutations compared to the normal exon 10 sequence. Due to the polymorphic sequence of the 3′ intron 9 sequence, it may appear difficult to sequence exon 10 and some mutations described in this exon could, in fact, be variations observed in an ectopic duplicated sequence.In our previous work we described a methodology to carry out PCR only of exon 10 and not of ectopic regions. In this work, we analyzed mutations described in the CF data base as being CFTR mutations but also found in ectopic regions: c.1392G>T, c.1338_1339delAT, c.1235delC, and c.1247A>G. We have shown that these mutations appear to be authentic mutations in CFTR exon 10 and not ectopic variations in analyzed patients. These mutations validate the usefulness of our new strategy in the mutation analysis of this region of CFTR.     

Fifty years of Fusarium: how could nine species have ever been enough?

Fusarium is globally one of the most important genera of fungi, causing an array of plant diseases, producing mycotoxins and adversely affecting human health. The genus is taxonomically complex and accurate identification requires a suite of different morphological, biological and phylogenetic markers. Herein we review some of the major advances in our knowledge of Fusarium that have occurred over the past 50 years.     

Optimizing laparoscopic splenectomy

Background: Laparoscopic splenectomy (LS), like other advanced laparoscopic procedures, is still an evolving procedure. The indications for surgery, criteria for patient selection, and operative technique are not yet well defined. We have therefore modified the standard technique for performing LS in an attempt to optimize the procedure. Methods: Over the past 2 years, we have performed LS in 59 patients. The last 43 patients were operated using a standardized technique that we believe to be optimal. It includes the routine use of the right lateral position, operating through three trocars, the mass transection of the splenic vasculature with a vascular endoscopic stapler, and the use of a self-retaining retrieval bag. Results: The average operating time was 79 min. Average blood loss was 95 cc, and average postoperative hospitalization was 2.3 days. There was one intraoperative complication and one postoperative complication. These results are superior to those we achieved earlier in our own experience, as well as to similar series that have been published recently. Conclusions: In our experience, the use of this new technique resulted in relatively short procedures with low morbidity. We believe that these results justify the use of LS as the procedure of choice for elective splenectomy in patients with normal or moderately enlarged spleens.     

The difficulty in selecting patients for cytoreductive nephrectomy: An evaluation of previously described predictive models

Purpose

To externally evaluate a preoperative points system and a preoperative nomogram, both created to assess time to death after cytoreductive nephrectomy (CN).

Mycobacterium fortuitum skin infection as a complication of anabolic steroids: a rare case report

Mycobacterium fortuitum is a rare cause of recurrent skin abscesses in an immunocompetent person. We report the case of a 37-year-old man presenting with multiple recurrent non-healing skin abscesses. Culture of the abscess wall yielded growth of M fortuitum. In our case, we highlight the association of anabolic steroids with non-tuberculous mycobacterial skin abscesses that fail to resolve despite repeated drainage.     

Incidence of post-traumatic seizures in children during combat operations in Afghanistan and Iraq

ObjectivesChildren represent a significant portion of the patient population treated at combat support hospitals. There is significant data regarding post injury seizures in adults but with children it is lacking. We seek to describe the incidence of post-traumatic seizures within this population.MethodsThis is a secondary analysis of previously described data from the Department of Defense Trauma Registry (DODTR). Within our dataset, we searched for documentation of seizures after admission.ResultsOf the 3439 encounters in our dataset, we identified 37 casualties that had a documented seizure after admission. Most were in the 1–4 year age group (37.8%), male (59.4%), injured by explosive (40.5%), with serious injuries to the head/neck (75.6%). The median ISS was higher in the seizure group (22 versus 10, p<0.001). Most survived to hospital discharge with no statistically significant increased mortality noted in the seizure group (seizure 90.2% versus 91.8%, p = 1.000). In the prehospital setting, the seizure group was more frequently intubated (16.2% versus 6.0%, p = 0.023), received ketamine (20.0% versus 3.2%, p<0.001), and administered an anti-seizure medication (5.4% versus 0.1%, p = 0.001). In the hospital setting, the seizure group was more frequently intubated (56.7% versus 17.7%, p<0.001), had intracranial pressure monitoring (24.3% versus 2.6%, p<0.001), craniectomy (10.8% versus 2.5%, p = 0.014), and craniotomy (21.6% versus 4.7%, p<0.001).ConclusionsWithin our dataset, we found an incidence of 1% of pediatric casualties experiencing a post-traumatic seizure. While this number appears infrequent, there is likely significant under detection of subclinical seizures.     

Phenotypic drug screening and target validation for improved personalized therapy reveal the complexity of phenotype-genotype correlations in clear cell renal cell carcinoma

ObjectivesNovel personalized therapeutic approaches are urgently needed for patients with metastatic clear cell renal cell carcinoma (ccRCC).Methods and materialsWe combined the development of a primary patient-derived ccRCC cell line with a phenotypic drug screen consisting of 101 approved anticancer compounds.ResultsWe identified the MNNG HOS transforming gene (MET)-anaplastic lymphoma receptor tyrosine kinase (ALK) inhibitor crizotinib as the top hit of our drug screen, whereas compounds targeting the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway showed no or only minor in vitro activity. Among the known major crizotinib targets MET, ALK, and ROS-1, only MET was expressed in our ccRCC cell line. Subsequent sequence analysis revealed a heterozygous R988C mutation of the MET gene and a VHL deletion in both the primary tumor and the tumor-derived ccRCC cell line. However, we were unable to show an activation of MET and, further, MET knockdown did not result in increased apoptosis or cytotoxicity. Therefore, our results suggest that MET R988C does not function as a major oncogenic driver mutation but rather represents a sequence variant. However, we provide evidence that the cytotoxic effect of crizotinib in our cell line model correlates with its ability to inhibit P-glycoprotein (ABCB1)-associated transport functions.ConclusionsOur study shows that a phenotypic screen of a patient-derived tumor cell line can identify compounds with antitumor activity but with an unexpected mode of action. Our results underscore that target validation and phenotype-genotype correlations remain a major experimental challenge. The implications of our findings for a personalized management of patients with cancer are discussed.     

Heat-killed probiotic Lactobacillus plantarum affects the function of neutrophils but does not improve survival in murine burn injury

Probiotics have become of interest as therapeutics in trauma or sepsis-induced inflammation due to their ability to affects the immune response. However, their use is still under debate due to the potential risk of septicemia. Therefore, heat-killed probiotics offer a potential alternative, with recent research suggesting a comparable immunomodulating potential and increased safety. In a previous study, we demonstrated decreased mortality by administration of live Lactobacillus plantarum in a mouse burn-sepsis model. Neutrophils are an essential innate defense against pathogens. Therefore, our present study aims to understand the impact of heat-killed probiotic L. plantarum (HKLP) on neutrophil function. Utilizing an in vitro stimulation with HKLP and a burn-infection in vivo model, we determined that administration of HKLP induced significant release of granulocyte-colony stimulating factor (G-CSF) and stimulated the release of pro-and anti-inflammatory cytokines. HKLP had no impact on neutrophil function, such as phagocytosis, oxidative burst, and NETosis, but increased apoptosis and activated neutrophils. HKLP did not improve survival. Together, contrary to our hypothesis, heat-killed probiotics did not improve neutrophil function and survival outcome in a murine severe burn injury model.     

Organ Donation: With Great Power Comes Great Responsibility

Spain is a world leader in donation and transplantation. This model has been exported to other countries with favorable results. The objective of this study was to compare the actual donation intention rate with the effective donation figures, and analyze the main reasons why families decline organ donation. To estimate the current donation intention, we conducted 1065 surveys in March 2019, and to calculate effective donation figures in our hospital, we analyzed 1158 interviews conducted with relatives of potential organ donors between 1996 and 2018. Regarding the surveys to estimate donation intention, the mean (standard deviation) age was 51.6 (17-91) years. A total of 58% were women, 26% were health care professionals, and 5.1% were transplant recipients; 89.4% would donate their organs. In the multivariate analysis, having expressed the desire to donate to their family was independently related to the intention to donate (odds ratio, 3.4; 95% confidence interval, 2.2-5.2; P < .001). Regarding the interviews with relatives of potential donors, 79.4% were finally effective donors. The belief that the possible donor would have rejected the organ donation stands out among the causes of decline. However, only one-half of those surveyed expressed the wish to be a donor to their relatives. In the temporal evolution, a greater acceptance of donation is observed in the first period with a reduction over the last years (P > .001). It is our responsibility to improve transplantation rates because our model has shown to save lives and it is a role model for other nations, promoting information activities that encourage greater discussion of organ donation within families.     

Complications and Graft Survival in Kidney Transplants With Vascular Variants: Our Experience and Literature Review

Introduction

In the literature several reconstructive techniques for vascular anastomoses in case of kidney graft vascular variants are reported. This article reports our experience in kidney transplants with vascular anomalies.

Materials and methods

Between January 1996 and June 2012, 154 cadaveric kidney transplantations were performed at our center. In 35 case, vascular variants were found. Among the arterial variants we observed 27 double arteries, 2 cases with 3 arteries, and 1 case with 4 arteries. All cases of Venous variants were double veins. Based on the type of reconstructive technique used, we divided transplants into group A (n = 22) separate multiple arterial anastomoses; group B (n = 8) anastomosis on the aortic patch; group C (n = 4) single anastomosis in case of 2 arteries with a common ostium at the aortic origin. The venous variants were treated with ligation of the vein of smaller caliber.

Results

Kidney preparation to the back table lasted on average 50 minutes with no significant differences between the 3 groups and no significant timing increase compared to renal transplants without vascular anomalies (mean warm ischemia 40 minutes, range 30–60 minutes). The mean cold ischemia time was limited to 16 hours from the removal and the mean warm ischemia was 50 minutes (range 30–70 minutes). There were no differences in timing between group C and single anastomoses, whereas groups A and B showed mean warm ischemia time was slightly increased compared to group C (P < .05). There were no significant differences in terms of delayed upturn of graft function and graft survival between groups A, B, and C and compared to transplants without vascular anomalies.

Conclusions

In our series we observed similar results performing the reimplantation on aortic patch and separate multiple arterial anastomoses. Considering our experience, we believe that vascular variants are not an indication to exclude a graft for transplantation.     

De novo adamantinomatous craniopharyngioma with long-term pre-diagnostic imaging

Adamantinomatous craniopharyngioma has a bimodal age distribution occurring in children aged 5–15 years and less frequently in adults aged 45–60 years. The current embryogenetic hypothesis suggests that adamantinomatous craniopharyngioma (ACP) arises from epithelial remnants of the craniopharyngeal duct or Rathke's pouch. It is thought that this tumor exists early on during childhood but remains indolent, growing very slowly until it is diagnosed incidentally or due to symptoms. Recent reports of de novo development of ACP, however, have challenged this theory. Herein, we present a case of an incidentally discovered de novo adamantinomatous craniopharyngioma that was documented to arise de novo on serial MRIs performed for a different indication. To our knowledge, this is the first report of a middle-aged patient who is diagnosed with a de novo ACP documented with contrast-enhanced MRIs of the sella over a 16-year period. This case challenges our current understanding of the pathophysiology of adamantinomatous craniopharyngioma.