bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolving treatment landscape of advanced urothelial carcinoma
Authors: Andreev-Drakhlin Alexander Y. , Egoryan Goar , Shah Amishi Y. , Msaouel Pavlos , Alhalabi Omar , Gao Jianjun
Published: March 2021

Purpose of review

Bladder cancer is the 10th most common cancer in the world and the 6th most common cancer among men. In the past few years, several new agents have been approved for the treatment of urothelial tumors. In this paper, we review the evolving treatment landscape of advanced urothelial carcinoma (UC).

Recent findings

Since 2016, the Food and Drug Administration (FDA) has approved five immunotherapies targeting programmed cell death 1/programmed cell death 1 legend, an antinectin-4 antibody drug conjugate (ADC), and a fibroblast growth factor receptor (FGFR) inhibitor for the treatment of patients with advanced UC. Moreover, there are multiple targeted agents, immune checkpoint inhibitors (ICI), ADCs, and their combinations currently being tested in clinical studies with the goal of obtaining FDA approval.

Precision oncology efforts continue to advance our understanding of the UC biology and transform the existing treatment paradigms. An enlarging arsenal of treatment options promises further personalization of UC therapy.
Highlighting recent treatment advances in metastatic prostate cancer: expanding the treatment arsenal
Authors: Gourdin Theodore
Published: March 2021

Purpose of review

Present highlights from recent research examining the treatment of advanced prostate cancer.

Recent findings

Although debate remains about the optimal sequencing of docetaxel and novel androgen directed therapies in addition to androgen deprivation therapy (ADT) in the treatment of men with new metastatic prostate cancer, the novel LHRH antagonist relugolix seems poised to become an appealing option in a choice of initial ADT. Novel radioisotopes, genomically selected therapies, and immune therapy combinations show progress in opening up new treatment options for men with castration-resistant prostate cancer.

Although no clear consensus has emerged, evolving data continue to refine the selection of systemic therapies in treatment naïve metastatic prostate cancer. With potentially less cardiotoxic androgen deprivation therapies, novel radioisotopes, targeted pharmaceuticals, and immune therapy combinations, progress appears to be on the horizon in improving outcomes for men with advanced prostate cancer.
Supportive care centers: definition of excellence
Authors: Carla Ida Ripamonti , Maurizio Lucchesi
Published: March 2021

Purpose of review

The current review is relevant because despite significant progress in oncology, a large proportion of patients with cancer still experience morbidity and symptoms, resulting from the cancer and/or its treatment.

Recent findings

The main theme concerns the definition of excellence of Supportive Care centers based on the indications of the Multinational Association Supportive Care Cancer (MASCC) because there are no data in literature on this topic.

Supportive care centers provide assistance to cancer patients suffering for anticancer treatments-related adverse effects. This leads to patient management with immediate evaluation and treatment of symptoms and therefore with improvement of quality of life and survival. In addition, there is less use of emergency room and hospitalizations with consequent savings of resources. According to MASCC evaluation criteria, some types of centers could be excellent in supportive care in cancer. Size, number of treated patients, or academic presence are not mandatory for the certification of excellence. However, centrality of patient and assessment of patient's needs, dedicated organizational models to evaluate and treat the adverse effects of anticancer treatments, dedicated activity and multidisciplinary staff, teaching programs, and adherence to guidelines are milestones for good clinical practices and consequently the centers that practice them represent the excellence in supportive care in cancer.
Teaching supportive care: what is the core curriculum?
Authors: Herrstedt Jørn , Molassiotis Alex
Published: March 2021

Purpose of review

Cancer treatment options have developed rapidly in the past years. Targeted- and immune therapy have resulted in additional supportive care needs. This review describes a teaching program in supportive care.

Recent findings

Supportive care begins at the time of cancer diagnosis and continues until the patient has died or is cured and late toxicities and other survivorship issues have been properly addressed. Supportive care is divided into four phases. In the curative phase, competences regarding prevention and management of acute treatment and subacute treatment side effects are important. In the survivorship phase, competences related to late toxicity and chronic toxicity are warranted. In the palliative phase, focus will be on competences concerning cancer complications, and specific end-of-life competences are needed as well. Obviously some competences are needed in all phases, for example, communication skills.

Competences concerning symptoms and complications are summarized for each phase in table format. General competences are listed in the text body of the manuscript. Regular update and implementation is crucial. The future cancer population will consist of a higher number of older cancer patients and survivors. This should reflect curriculum updates as should the increasing possibilities for multigene sequencing enabling personal medicine (including supportive care) to a larger extent than today.
Standardization and Selection of High-risk Patients for Surgical Wound Infections in Plastic Surgery
Authors: Starnoni Marta , Pinelli Massimo , Porzani Silvia , Baccarani Alessio , De Santis Giorgio
Published: March 2021

Background:

The aim of the present study was to show that the Infection Risk Index (IRI), based on only 3 factors (wound classification, American Society of Anesthesiologists score, and duration of surgery), can be used to standardize selection of infection high-risk patients undergoing different surgical procedures in Plastic Surgery.

Methods:

In our Division of Plastic Surgery at Modena University Hospital, we studied 3 groups of patients: Group A (122 post-bariatric abdominoplasties), Group B (223 bilateral reduction mammoplasties), and Group C (201 tissue losses with first intention healing). For each group, we compared surgical site infection (SSI) rate and ratio between patients with 0 or 1 risk factors (IRI score 0 or 1) and patients with 2 or 3 risk factors (IRI score 2 or 3).

Results:

In group A, patients with IRI score 0–1 showed an SSI Ratio of 2.97%, whereas patients with IRI score 2–3 developed an SSI ratio of 27.27%. In group B, patients with IRI score 0–1 showed an SSI ratio of 2.99%, whereas patients with IRI score 2–3 developed an SSI ratio of 18.18%. In group C, patients with IRI score 0–1 showed an SSI ratio of 7.62%, whereas patients with IRI score 2–3 developed an SSI ratio of 30.77%.

Conclusions:

Existing infection risk calculators are procedure-specific and time-consuming. IRI score is simple, fast, and unspecific but is able to identify patients at high or low risk of postoperative infections. Our results suggest the utility of IRI score in refining the infection risk stratification profile in Plastic Surgery.
Barriers to Accessing Mental Health Care After a Sexual Assault Medical Forensic Examination
Authors: Gilmore Amanda K. , Leone Ruschelle M. , Hahn Christine K. , Oesterle Daniel W. , Davidson Tatiana M.
Published: March 2021

Background

Research indicates low rates of accessing mental health care following sexual assault; however, barriers associated with accessing care are not well understood.

Design

Participants (N = 37) were recruited from a local hospital following a sexual assault medical forensic examination (SAMFE). Hierarchical linear regressions models examined the effects of age, racial identity, student status, insurance status, relationship to perpetrator, time since assault, problematic drinking, and posttraumatic stress symptoms on (a) barriers to accessing care and (b) the likelihood of seeking mental health treatment at no charge.

Results

Lack of insurance was associated with more barriers to accessing mental health care and a higher likelihood of seeking post-SAMFE care at no charge. Posttraumatic stress symptoms were associated with more barriers to accessing care (p = 0.038). Identifying as a student (p = 0.026) and engaging in problematic drinking (p = 0.047) were associated with a lower likelihood of seeking post-SAMFE care, whereas increased symptoms of posttraumatic stress were associated with a greater likelihood of seeking post-SAMFE care (p = 0.007).

Conclusions

Providing post-SAMFE care, irrespective of insurance, may be a needed first step in addressing the mental health needs of individuals with recent sexual assault. Secondary prevention programs targeted toward alcohol misuse may also be warranted.
Coexistence of Sjögren syndrome in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome
Authors: Wang Lun , Yu Yanying , Zhang Shuo , Zhang Wen , Li Chen
Published: March 2021

To identify the prevalence and clinical characteristics of Sjögren syndrome (SS) in a Chinese single-center cohort of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.

Patients diagnosed with SS were screened out from a cohort of 164 cases of SAHPO syndrome. Information regarding the patients’ gender, age at onset, clinical features, laboratory tests, bone scintigraphy, and treatment was reviewed.

Five patients were screened out. The prevalence of SS in SAPHO patients was 3.05% The mean onset age of SS was 48.0 ± 12.0 years old and no apparent time order in the occurrence of SAPHO and SS was observed. Compared with the general SAPHO cohort, the 5 SS patients exhibited no significant difference in the SAPHO related clinical features or inflammatory markers, except for a higher prevalence of peripheral joints and bones involvement in bone scintigraphy. Objective evidence of dryness and positive salivary gland biopsy were found in all the patients. However, the positive rates of SSA and SSB antibody were only 20%. Anti-inflammatory treatment for SS was recorded in 3 patients (ESSDAI score: 3 in 2 patients; 12 in 1 patient) with extra-glandular manifestations, severe complications or poor response to the basic treatment.

The prevalence of SS is higher in the SAPHO cohort than in the general Chinese population. Objective tests or biopsy might be more indicative than the antibody detection for SS diagnosis. Anti-inflammatory treatment should be prescribed in consideration of both the severity of SS and the demand for disease activity control of SAPHO.
Osteotomy combined with lateral ligament reconstruction in treating osteochondral lesion in patients with talar injury and varus ankle
Authors: Hu Mu , Xu Xiang-Yang
Published: March 2021

This study aimed to investigate the therapeutic effects of osteotomy combined with lateral ligament reconstruction on the osteochondral lesion of patients with talar injuries and varus ankles.

Seventy five patients with talar injuries and varus ankles who received osteotomy combined with lateral ligament reconstruction for the osteochondral lesions from June 2008 to December 2014 were retrospectively reviewed. Patients were followed up for 32.4 ± 15.3 months after surgeries, and the AOFAS-AH score, VAS score and SF36 score were determined preoperatively and postoperatively. The iconographic data were compared preoperatively and postoperatively, including tibial anterior surface angle (TAS), TTS, TT, and tibial lateral surface angle (TLS) angles.

After surgeries, the AOFAS-AF score increased from 43.2 ± 8.1 to 82.1 ± 5.6, the VAS score decreased from 6.9 ± 2.3 to 1.8 ± 1.5, and the SF36 score increased from 48.7 ± 9.4 to 83.5 ± 6.2. TAS increased from 83.3 ± 5.1 to 90.3 ± 6.1, TTS increased from 70.3 ± 6.1 to 82.5 ± 5.4, TT decreased from 12.9 ± 6.1 to 6.9 ± 5.7, and TLS increased from 76.5 ± 4.1 to 81.2 ± 3.3 (P < .05).

Osteotomy combined with lateral ligament reconstruction is effective for the treatment of talar osteochondral lesion with varus ankle, which could relieve the arthritic symptoms induced by cartilage lesions. By correcting the force line on lower limbs and metapedes with osteotomy completely, the treatments on talar osteochondral lesion and lateral ligament reconstruction are the critical factors with better results.
Effects of STC on postoperative recovery of disturbance of consciousness in traumatic multiple intracranial hematoma patients
Authors: Wang Dan , Zhou Zhulin , Zhang Bingjie , Zhang Bo , Yang Hongfa
Published: March 2021

Objective:

The study explored the therapeutic value of standard trauma craniectomy (STC) for the treatment of traumatic multiple intracranial hematoma.

Methods:

Clinical data of traumatic multiple intracranial hematoma patients who underwent surgical treatment in 2014 and 2015 were collected. The STC group and a control group according to the surgical mode, 48 and 30 cases were randomly selected from each group, respectively. Statistical analysis was performed on the change in the Glasgow coma scale (GCS) score from before the operation to 1 day, 1 week and 1 month postoperatively through repeated analysis of variance and Wilcoxon rank-sum analysis.

Results:

Significant differences in the GCS were observed at different time points for the two operative modes (P < .01), and an interaction was observed between time and treatment groups (P < .05). The rates of change of the GCS score for the two surgical modes were most obviously different at 3 days and 1 week postoperatively (P ≤ .001, P < .01). No statistically significant differences were observed in the rates of change of the GCS at 1 month postoperatively (P > .05).

Conclusions:

Compared to conventional craniotomy, STC has obvious effects on the recovery after disturbance of consciousness at 1 week postoperatively but does not result in a significant improvement in recovery at 1 month postoperatively.
Clinical seizures and unfavorable brain MRI patterns in neonates with hypoxic ischemic encephalopathy
Authors: Lin Yen-Kuang , Hwang-Bo Seok , Seo Yu-Mi , Youn Young-Ah
Published: March 2021

The aim was to examine whether clinical seizures and amplitude-integrated electroencephalogram (aEEG) patterns in infants with hypoxic ischemic encephalopathy (HIE) can predict the extent of brain injury on magnetic resonance images (MRI) and the long-term neurodevelopmental outcomes at 18∼24 months of age.

HIE infants who underwent therapeutic hypothermia (TH) between June 2014 and March 2017 were included in this study. Infants with clinical seizure were analyzed for aEEG patterns and the extent of brain injury on MRI findings. Clinical seizure, aEEG, and brain MRI were assessed and compared with neurodevelopmental outcomes at 18∼24 months of age.

Among the 97 HIE infants enrolled in this study with brain MRI scans, 78 (73.1%) TH-treated HIE infants exhibited clinical seizures. More abnormalities on a EEGs and more significant use of first and second antiepileptic drugs (AEDs) were significantly higher in the clinical-seizure group with longer hospitalized days. At a corrected 18 to 24 months of age, HIE infants in the clinical-seizure group with more extension of injury lesions on diffusion-weighted MRI scans exhibited significantly more delayed neurodevelopment. A risk factor analysis indicated that male infants who stayed in the hospital for more than 11 days were at a higher risk of having clinical seizures. The lesion size in MRI greater than 37 pixels was a risk factor with an 81.8% accuracy.

Seizures in HIE infants may predict abnormal brain MRI scans and abnormal neurodevelopment at 18 to 24 months of age.
Pre-operative echocardiograms in acute fragility hip fractures
Authors: AbuSharar Shady Piedra , Bess Leah , Hennrikus Eileen
Published: March 2021

In 2014, the American College of Cardiology/American Heart Association (ACC/AHA) released guidelines for ordering pre-operative echocardiograms in patients undergoing non-cardiac surgery. The purpose of this study is to determine if pre-operative echocardiograms ordered prior to fragility hip fracture repair are ordered according to these guidelines, change anesthetic management or affect patient outcomes. In addition, we attempted to evaluate the efficacy of the ACC/AHA guidelines.

We conducted a 4-year retrospective chart review of acute fragility hip fractures at a single institution. Charts were reviewed to determine which patients met criteria for a pre-operative echocardiogram. Within this group we then compared patients who received a pre-operative echocardiogram to those who did not. Comparisons were made with regard to time to surgery, changes from standard anesthetic management, major adverse cardiac events, length of hospital stay, and 1-year mortality. We also examined which patients received postoperative echocardiograms and the incidence of adverse cardiac events in this group.

Of 402 patients, 87 (22%) had ACC/AHA indications for pre-operative echocardiogram, and 42 (48%) of them received one. The indication to order a pre-operative echocardiogram in stable heart failure or valve disease patients if their last echo was greater than 1 year was only followed 23% of the time. In the pre-operative echocardiogram group, anesthetic management was adjusted more frequently (P = .025), and average time to surgery was greater (P < .001). The incidence of a major adverse cardiac event was 10% in the ACC/AHA echocardiogram indicated group and 3% in the non-indicated echocardiogram group. An equal number of echocardiograms were completed postoperatively as were completed under ACC/AHA pre-operative guidelines. Sixty-seven percent of the postoperative echocardiograms did not have ACC/AHA pre-operative indications.

Our data demonstrates that pre-operative echocardiograms for “stable heart failure and valvular disease with greater than 1 year from last echocardiogram” is infrequently performed without significant adverse cardiac outcomes. Pre-operative echocardiography was associated with more anesthetic adjustments and longer time to surgery. Postoperative echocardiograms were done for cardiopulmonary complications. Studies need to examine and refine clinical parameters that would improve the selection of patients who would benefit from pre-operative echocardiograms.
Association of serum vaspin, apelin, and visfatin levels and stroke risk in a Chinese case-control study
Authors: Yu Dalin , Huang Bin , Wu Bin , Xiao Jun
Published: March 2021

Adipose tissue acts as an active endocrine organ secreting a number of adipokines and may be involved in biological mechanism of stroke. Vaspin, apelin, and visfatin play important roles in the regulation of vascular disorders.

Our aim was to evaluate whether the concentrations of vaspin, apelin, and visfatin were associated with stroke risk.

A total of 235 patients with stroke (156 patients with ischemic stroke and 79 patients with hemorrhagic stroke) and 235 age- and gender-matched healthy controls were included in this study. A sandwich ELISA was developed to measure the serum vaspin, apelin, and visfatin levels.

There was a statistically significant difference in the median levels of serum vaspin, apelin, and visfatin levels between stroke cases and controls (vaspin: 1.50 vs 1.07 ng/ml; apelin: 1.56 vs 1.32 pg/ml; visfatin: 23.40 vs 19.65 ng/ml; all P values <.001). Multiple logistic regression analysis showed that, serum vaspin and visfatin levels were significantly inversely associated with increased risk of stroke, and the odds ratios (ORs) in the highest tertile were 2.25 [95% confidence interval (CI) 1.38–3.67; P for trend <.001] for vaspin and 2.56 (95% CI 1.46–4.47; P for trend <.001) for visfatin, respectively, compared with the lowest tertile. Higher apelin levels were marginally associated with lower stroke risk (P for trend =.060).

Our study indicated that higher vaspin, apelin, and visfatin levels might be associated with increased stroke risk. Necessary prospective cohort studies should be conducted to confirm this association in the future.
Low‐Risk Human Leukocyte Antigen Genes and Mild Villous Atrophy Typify Celiac Disease With Immunoglobulin A Deficiency
Authors: Schirru Enrico , Jores Rita Désirée , Rossino Rossano , Corpino Mara , Cucca Francesco , Congia Mauro
Published: March 2021

Objectives:

We aimed to establish if in celiac disease (CD) with immunoglobulin A deficiency (IgAD) duodenal histopathology is influenced by human leukocyte antigen (HLA)‐DQB1*02 alleles dosage. Clinical differences between patients with CD and patients with CD and IgAD (CD‐IgAD) were also evaluated.

Methods:

Five hundred and sixteen CD and 16 patients with CD‐IgAD, enrolled over the time of 8 years, took part in this study. The severity of duodenal histopathology and frequency of CD at‐risk HLA class II genes were compared in patients with CD versus patients with CD‐IgAD. HLA class II genotypes were subdivided into two categories of genetic risk: high: HLA‐DR3/DR7, ‐DR3/DR3, ‐DR4/DR4 ‐DR3/DR4 and low: HLA‐DR5/DR7, ‐DR3/X, ‐DR4/X and X/X, where X means neither ‐DR3 nor ‐DR4. Then, they were compared with two types of duodenal histopathology: 0, 1, 2 and 3a of mild villous atrophy (MVA) and 3b and 3c of severe villous atrophy (SVA) according to the Marsh‐Oberhuber classification. Clinical data concerning gender, number of esophagogastroduodenoscopies (EGDs) and association with other autoimmune diseases were obtained from medical records.

Results:

In comparison with CD, CD‐IgAD showed an increased frequency of MVA (P < 0.0001). Furthermore, CD‐IgAD with MVA showed an increase of HLA low‐risk genotypes (P = 0.036) and half HLA‐DQ2 heterodimers (P = 0.0443). Interestingly, CD‐IgAD demanded an increased number of EGDs to reach the diagnosis of CD (P = 0.0104) and autoimmune liver diseases were more frequent compared to CD (P = 0.0049).

Conclusions:

CD‐IgAD is associated with MVA, low‐risk HLA class II genes, an increased number of EGDs and autoimmune liver diseases.
Peritoneovenous Shunt for Intractable Ascites in Children
Authors: Defert Coralie , Marret Jean‐Baptiste , Lacaille Florence , Sissaoui Samira , Dupic Laurent , Lardy Hubert , Capito Carmen , Chardot Christophe
Published: March 2021

Intractable ascites is a rare condition in children mainly caused by cirrhosis or lymphatic disorders. Internal drainage may be considered as rescue therapy. In our department, 4 patients ages from 2 months to 15 years old underwent a peritoneovenous shunt (PVS) placement between 2010 and 2020. The surgically inserted device was a pumping device that enabled to drain ascites from the peritoneum into the venous system via the internal jugular vein (Denver shunt, BD Company, NJ). Immediate efficient drainage was achieved in all cases and lasted up to 9 years. Two major complications occurred: a postoperative fat embolism requiring urgent temporary ligation of the shunt and endocarditis shortly after inguinal hernia repair performed 16 months after placement of the shunt. Implementation of a PVS may be a useful procedure in patients with refractory ascites. Chylous ascites should be drained and washed totally before activating the device to avoid fat embolism. Antibiotic prophylaxis is required when abdominal surgery is planned while the device is in place.
The Versatility of the Pedicled Medial Sural Artery Perforator Flap: From Simple to Its Chimeric Pattern and Clinical Experience with 37 Cases
Authors: Scaglioni Mario F. , Rodi Timo , Fritsche Elmar
Published: March 2021

Background:

Defects in the knee area, popliteal fossa region, and upper third of the lower extremity can pose a challenge for reconstructive plastic surgeons. The purpose of this article is to report the authors’ experience with the use of the pedicled medial sural artery perforator flap in its simple and chimeric form for reconstruction of defects in three different regions: knee, popliteal fossa, and proximal lower leg.

Methods:

From April of 2018 to April of 2019, 37 patients (29 men and eight women) with a mean age of 51 years (range, 18 to 78 years) underwent reconstruction with 37 pedicled medial sural artery perforator flaps. All flaps were harvested as pedicled perforator flaps in conventional or chimeric fashion and were based on one or two perforators. The defect locations included the knee (18 cases), popliteal fossa (seven cases), and proximal lower leg (12 cases). The cause of reconstruction was trauma in 22 patients (59 percent), tumor in 10 patients (27 percent), and donor-site closure of free medial sural artery perforator in five patients (14 percent).

Results:

The flap sizes varied from 3.5 × 5 cm to 5 × 10 cm. All but one flap, which showed distal tip necrosis, survived completely after surgery. The donor sites were all closed primarily. Minor complications included flap dehiscence (two cases) and minor wound infection delaying the healing process (four cases). All complications were treated conservatively. Follow-up observations were conducted for 3 to 12 months, and all patients had good functional recovery with satisfactory cosmetic results.

Conclusion:

The pedicled medial sural artery perforator flap can be considered an optimal method of reconstruction for covering defects not only in the knee area but also in the popliteal fossa and upper lower leg.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
The burden of readmission after discharge from necrotizing soft tissue infection
Authors: Toraih Eman , Hussein Mohammad , Tatum Danielle , Reisner Adin , Kandil Emad , Killackey Mary , Duchesne Juan , Taghavi Sharven
Published: March 2021

BACKGROUND

The need for extensive surgical debridement with necrotizing soft tissue infections (NSTIs) may put patients at high risk for unplanned readmission. However, there is a paucity of data on the burden of readmission in patients afflicted with NSTI. We hypothesized that unplanned readmission would significantly contribute to the burden of disease after discharge from initial hospitalization.

METHODS

The Nationwide Readmission Database was used to identify adults undergoing debridement for NSTI hospitalizations from 2010 to 2017. Risk factors for 90-day readmission were assessed by Cox proportional hazards regression.

RESULTS

There were a total of 82,738 NSTI admissions during the study period, of which 25,076 (30.3%) underwent 90-day readmissions. Median time to readmission was 25 days (interquartile range, 9–49 days). Fragmentation of care, longer length of index stay (>2 weeks), and Medicaid status were independent risk factors for readmission. Median cost of a readmission was US $10,543. Readmission added 174,640 hospital days to episodes of care over the study period, resulting in an estimated financial burden of US $1.4 billion.

CONCLUSION

Unplanned readmission caused by NSTIs is common and costly. Interventions that target patients at risk for readmission may help decrease the burden of disease.

LEVEL OF EVIDENCE

Economic/Epidemiological, level IV.
Deep immune profiling of whole blood to identify early immune signatures that correlate to patient outcome after major trauma
Authors: Mendoza April E. , Raju Paul Susan , El Hechi Majed , Naar Leon , Nederpelt Charlie , Mikdad Sarah , van Erp Inge , Hess Joshua M. , Velmahos George C. , Poznansky Mark , Reeves Patrick
Published: March 2021

BACKGROUND

Major injury results in an early cascade of immunologic responses that increase susceptibility to infection and multiorgan dysfunction. Detailed immune profiling by mass cytometry has the potential to identify immune signatures that correspond to patient outcomes. Our objective was to determine the prognostic value of immune signatures early after major trauma injury.

METHODS

Trauma patients (n = 17) were prospectively enrolled between September 2018 and December 2019. Serial whole blood samples were obtained from trauma patients (mean Injury Severity Score, 26.2; standard error of the mean, 3.7) at Days 1 and 3 after injury, and from age- and sex-matched uninjured controls using a standardized protocol for fixation, storage, and labeling. Computational analyses including K-nearest neighbor automated clustering of immune cells and Spearman’s correlation analysis were used to identify correlations between cell populations, clinical measures, and patient outcomes.

RESULTS

Analysis revealed nine immune cell clusters that correlated with one or more clinical outcomes. On Days 1 and 3 postinjury, the abundance of immature neutrophil and classical monocytes exhibited a strong positive correlation with increased intensive care unit and hospital length of stay. Conversely, the abundance of CD4 T-cell subsets, namely Th17 cells, is associated with improved patient outcomes including decreased ventilator days (r = −0.76), hospital-acquired pneumonia (r = −0.69), and acute kidney injury (r = −0.73).

CONCLUSION

Here, we provide a comprehensive multitime point immunophenotyping analysis of whole blood from patients soon after traumatic injury to determine immune correlates of adverse outcomes. Our findings indicate that alterations in myeloid-origin cell types may contribute to immune dysfunction after injury. Conversely, the presence of effector T cell populations corresponds with decreased hospital length of stay and organ dysfunction. Overall, these data identify novel immune signatures following traumatic injury that support the view that monitoring of immune (sub)-populations may provide clinical decision-making support for at-risk patients early in their hospital course.

LEVEL OF EVIDENCE

Prognostic/Epidemiologic, Level IV.
Characterization of presumptive vancomycin-resistant enterococci recovered during infection control surveillance in Dallas, Texas, USA
Authors: Ping Sara , Mayorga-Reyes Nancy , Price Valerie J. , Onuoha Michelle , Bhardwaj Pooja , Rodrigues Marinelle , Owen Jordan , Palacios Araya Dennise , Akins Ronda L. , Palmer Kelli L.
Published: March 2021

Enterococcus faecalis

and

E. faecium

are Gram-positive bacteria that normally inhabit the human gastrointestinal tract. They are also opportunistic pathogens and can cause nosocomial infection outbreaks. To prevent the spread of nosocomial infections, hospitals may rely on screening methods to identify patients colonized with multidrug-resistant organisms including vancomycin-resistant enterococci (VRE). Spectra VRE agar (Remel) contains vancomycin and other medium components that select for VRE and phenotypically differentiate between

E. faecalis

and

E. faecium

by colony colour. We obtained 66 de-identified rectal swab cultures on Spectra VRE agar that were obtained during routine patient admission surveillance at a hospital system in Dallas, Texas, USA. We analysed 90 presumptive VRE from 61 of the Spectra VRE agar cultures using molecular and culture methods. Using ddl typing, 55 were found to be

E. faecium

and 32 were found to be

E. faecalis

. While most of the

E. faecium

were positive for the vanA gene by PCR (52 of 55 strains), few of the

E. faecalis

were positive for either vanA or vanB (five of 32 strains). The 27 E. faecalis vanA- and vanB-negative strains could not be recultured on Spectra VRE agar. Overall, we found that Spectra VRE agar performed robustly for the identification of vancomycin-resistant

E. faecium

, but presumptive false positives were obtained for vancomycin-resistant

E. faecalis

.
Oncogenic human papillomavirus in breast cancer: molecular prevalence in a group of Congolese patients
Authors: Boumba Anicet Luc Magloire , Malanda Mboungou Moudiongui Dimitri , Ngatali Sidney Frousse Christian , Takale Ragive Parode , Moukassa Donatien , Peko Jean Félix
Published: March 2021

Background. Since the work of Band et al. in 1990 (Proc. Natl. Acad. Sci. USA 87:463–467), several studies have suggested a possible link between the pathogenesis of breast cancer and viral infection. Infection with oncogenic HPV has been one of the viruses implicated in breast cancer cases worldwide.

Objective. To investigate the presence of HPV DNA in archived paraffin-embedded breast cancer cases at the University Hospital of Brazzaville and to assess the association between viral HPV infections and clinicopathological features.

Methods. A total of 40 formalin-fixed paraffin-embedded (FFPE) biopsies were retrospectively collected and available information was recorded. HPV detection and genotyping were performed by real-time PCR by GeneXpert technology (Cepheid, Sunnyvale, USA).

Results. The mean age was 51.1±11.4 years (range 22–75 years; median was 47). Overall, HPV DNA was detected in six (15%) breast carcinoma samples. HPV-16, the most common genotype was identified in 83.7 % of all samples. HPV porting with clinicopathological features showed no significant difference (P>0.05). However, a statistically significant difference was observed between HPV infection and SBR grade (P=0.05).

Conclusion. Our study described a high prevalence of HPV-HR in breast cancer cases in the Congolese woman. Future type case-control studies are necessary to better describe the potential role of HPV in the occurrence of breast cancer in Congo.
Complete loss of CASK causes severe ataxia through cerebellar degeneration in human and mouse
Authors: Patel Paras A , Hegert Julia , Cristian Ingrid , Kerr Alicia , LaConte Leslie EW , Fox Michael A , Srivastava Sarika , Mukherjee Konark
Published: March 2021

Heterozygous loss of X-linked genes like CASK and MeCP2 (Rett syndrome) causes neurodevelopmental disorders (NDD) in girls, while in boys such loss leads to profound encephalopathy. The cellular basis for these disorders remains unknown. CASK is presumed to work through the Tbr1-reelin pathway in neuronal migration during brain development. Here we report our clinical and histopathological analysis of a deceased 2-month-old boy with a CASK-null mutation. We demonstrate that although smaller in size, the CASK-null human brain exhibits normal lamination without defective neuronal differentiation, migration, or axonal guidance, excluding the role of reelin in CASK-linked pathology. The disproportionately hypoplastic cerebellum in humans without CASK expression is associated with cerebellar astrogliosis, a marker for neuronal loss. Cerebellum-specific deletion in mouse confirms a post-developmental degeneration of cerebellar granular neurons that results in a small cerebellum. Mechanistically, cerebellar hypoplasia in CASK mutation thus results from neurodegeneration rather that developmental defects. Zygosity-pathology correlation suggests that NDDs like CASK mutation and Rett syndrome are pathologically neurodegenerative; however, random X-chromosome inactivation in the typical heterozygous mutant girls results in 50% of cells expressing the functional gene, resulting in a non-progressive pathology, whereas complete loss of the only allele in boys leads to unconstrained degeneration and encephalopathy.

One sentence summary of study

CASK loss causes cerebellar degeneration. The authors have declared that no conflict of interest exists.
The late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for Lassa virus fusion
Authors: Markosyan Ruben M. , Marin Mariana , Zhang You , Cohen Fredric S. , Melikyan Gregory B.
Published: March 2021

Arenavirus entry into host cells occurs through a low pH-dependent fusion with late endosomes that is mediated by the viral glycoprotein complex (GPC). The mechanisms of GPC-mediated membrane fusion and of virus targeting to late endosomes are not well understood. To gain insights into arenavirus fusion, we examined cell-cell fusion induced by the Old World Lassa virus (LASV) GPC complex. LASV GPC-mediated cell fusion is more efficient and occurs at higher pH in cells expressing human LAMP1 compared to cells lacking this cognate receptor, but this receptor is not absolutely required for virus entry. GPC-induced fusion progresses through the same lipid intermediates as fusion mediated by other viral glycoproteins – a lipid curvature-sensitive intermediate upstream of hemifusion and a hemifusion intermediate downstream of acid-dependent steps that can be arrested in the cold. Importantly, GPC-mediated fusion is specifically augmented by an anionic lipid, bis(monoacylglycero)phosphate (BMP), which is highly enriched in late endosomes. We show that BMP promotes late steps of LASV fusion downstream of hemifusion – the formation and enlargement of fusion pores. This lipid also specifically promotes cell fusion mediated by GPC of the unrelated New World Junin arenavirus. The BMP-dependence of post-hemifusion stages of arenavirus fusion suggests that these viruses evolved to use this lipid as a cofactor to direct virus entry to late endosomes.

Author Summary

Pathogenic arenaviruses pose a serious health threat. The viral envelope glycoprotein GPC mediates attachment to host cells and drives virus entryviaendocytosis and low pH-dependent fusion within late endosomes. Understanding the host factors and processes that are essential for arenavirus fusion may identify novel therapeutic targets. To delineate the mechanism of arenavirus entry, we examined cell-cell fusion induced by the Old World Lassa virus GPC proteins at low pH. Lassa virus fusion was augmented by the LAMP1 receptor and progressed through lipid curvature-sensitive intermediates, such as hemifusion (merger of contacting leaflets of viral and cell membrane without the formation of a fusion pore). We found that most GPC-mediated fusion events were off-path hemifusion structures and that the transition from hemifusion to full fusion and fusion pore enlargement were specifically promoted by an anionic lipid, bis(monoacylglycero)phosphate, which is highly enriched in late endosomes. This lipid also specifically promotes fusion of unrelated New World Junin arenavirus. Our results imply that arenaviruses evolved to use bis(monoacylglycero)phosphate to enter cells from late endosomes.
Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP proteins
Authors: Hwang Theresa , Grant Robert A. , Ilunga Meucci W. , Sivaraman Venkatesh , Keating Amy E.
Published: March 2021

The human proteome is replete with short linear motifs (SLiMs) of 4-6 residues that are critical for protein-protein interactions, yet the importance of the sequence surrounding such motifs is underexplored. We devised a proteomic screen to systematically examine the influence of SLiM sequence context on protein-protein interactions. Focusing on the EVH1 domain of ENAH, an actin regulator that is upregulated in invasive cancers, we screened 36-residue proteome-derived peptides for binding. We discovered a pocket on the ENAH EVH1 domain that diverged from its orthologs to recognize extended SLiMs, and we found that proteins with two EVH1-binding SLiMs can wrap around a single domain. We also found that the ciliary protein PCARE uses an extended 23-residue region to obtain higher affinity than any known ENAH EVH1-binding motif. Our screen provides a way to uncover the effects of broader proteomic context on motif-mediated interactions, revealing diverse mechanisms of contextual control over EVH1 interactions and establishing that SLiMs can’t be fully understood outside of their native context.
A Multiscale Immuno-Oncology on-Chip System (MIOCS) establishes that collective T cell behaviors govern tumor regression
Authors: Ronteix Gustave , Jain Shreyansh , Angely Christelle , Cazaux Marine , Khazen Roxana , Bousso Philippe , Baroud Charles N.
Published: March 2021

T cell-based tumor immunotherapies such as CAR T cells or immune checkpoint inhibitors harness the cytotoxic potential of T cells to promote tumor regression. However, patient response to immunotherapy remains heterogeneous, highlighting the need to better understand the rules governing a successful T cell attack. Here, we develop a microfluidic-based method to track the outcome of T cell activity on many individual cancer spheroids simultaneously, with a high spatiotemporal resolution. By combining these parallel measurements of T cell behaviors and tumor fate with probabilistic modeling, we establish that the first recruited T cells initiate a positive feedback loop leading to an accelerated effector accumulation on the spheroid. We also provide evidence that cooperation between T cells on the spheroid during the killing phase facilitates tumor destruction. We propose that tumor destruction does not simply reflect the sum of individual T cell activities but relies instead on collective behaviors promoting both T cell accumulation and function. The possibility to track many replicates of immune-tumor interactions with such a level of detail should help delineate the mechanisms and efficacy of various immunotherapeutic strategies.
A discussion on `Domain formation and phase transitions in the wurtzite-based heterovalent ternaries: a Landau theory analysis'
Authors: Quayle Paul C. , Breternitz Joachim
Published: March 2021

Heterovalent ternary nitrides are considered one of the promising classes of materials for photovoltaics, combining attractive physical properties with low toxicity and element abundance. One of the front-runner systems under consideration is ZnSnN2. Although it is nominally a ternary compound, no clear crystallographic evidence for cation ordering has been observed so far. An attempt to elucidate this discrepancy [Quayle (2020). Acta Cryst. A76, 410–420] was the trigger for an intensive discussion between the authors, and an agreement was reached to elaborate on some points in order to set things in perspective. Rather than using a conventional comment–answer scheme, this is published in the form of a joint discussion to celebrate constructive criticism and collegiality.
(4-Aminopyridine-κN
1)(2,2′-bipyridine-κ2
N,N′)(2,2′:6′,2′′-terpyridine-κ3
N,N′,N′′)ruthenium(II) bis(hexafluoridophosphate) unknown solvate
Authors: Reed Carly R. , Garner Robert N. , Brennessel William W.
Published: March 2021

The title compound, [Ru(C5H6N2)(C10H8N2)(C15H11N3)](PF6)2 solvent, crystallizes in the triclinic space group P\overline{1} with one dicationic Ru complex, two PF6
− anions, and undefined solvent in the asymmetric unit. The cation and anions are linked via N—H...F hydrogen bonding. One PF6
− anion is disordered over two positions, with occupancies 0.634 (8) and 0.366 (8). The solvent, which is located in channels in the crystal, is highly disordered. Reflection contributions from the solvent were added to the calculated structure factors using the SQUEEZE routine [Spek (2015) Acta Cryst. C71, 9–18] of the program PLATON, which determined there to be 59 electrons in 264 Å3 treated this way per unit cell. Because the exact identity and amount of solvent were unknown, no solvent was included in the atom list or molecular formula.
Beleza Natural: Marketing Strategies for Empowering Social Change
Authors: Chernev Alexander , Kilibarda Vasilia
Published: March 2021

This case features an entrepreneur striving to rapidly grow a successful chain of hair salons that serve women with afro hair. After doubling from 13 to 26 salons across Brazil in 2014, the founders' expansion plan called for 120 Beleza Natural salons and R$1 billion in sales by 2018. CEO and cofounder Leila Velez is considering various fundamental marketing strategies to catalyze growth: Should Beleza launch a new mass-media campaign, increase promotional discounts, expand its target market to serve men, broaden its service offerings, streamline processes to reduce wait times, expand distribution channels, or franchise? Students assume the role of Velez and are asked to recommend which growth strategy would be their top priority. In doing so, they are required to evaluate how these strategies pertain to the company's business model and value proposition. They are also challenged to consider what a brand is and what makes a strong service brand in order to verify if their strategies are consistent with Beleza's brand. The teaching note outlines a framework for developing or evaluating a business model as well as developing strategies for managing growth. The case is accompanied by a series of video interviews with Velez that support case preparation, in-class discussion, and key learning points.
Coming from Behind: The Chicago Cubs' Resurgence as a 100-Year-Old Startup
Authors: Shein James B. , Meagher Evan
Published: March 2021

This “mini-case” summarizes the beloved Chicago Cubs' many years of futility and remarkable turnaround in the early teens of the twenty-first century. Central to the case is the concept that despite being an incredibly popular, billion-dollar franchise holding a special place in the hearts of Chicagoans for more than a century, the organization's sale from the Tribune Company in 2009 to the Ricketts family effectively required a full reboot of the company's infrastructure, akin to a startup or to a “carve-out” situation popular in the private equity world. The case resonates because the brand is easily recognizable in an industry with the unique dynamics of professional sports, and yet the company's situation features similarities to any lower-profile organization trying to build or rebuild its SG&A infrastructure from scratch.
Neighborhood Watch: The Rise of Zillow
Authors: Walker Russell
Published: March 2021

Read any news report on the housing market, and inevitably it will include facts or figures from the real estate data giant Zillow.com. The company initially set out to solve two key economic frictions in the real estate industry information asymmetry and the principal-agent problem by empowering users to access real-time housing data and eliminating the need for realtors. The company soon realized, however, that American homeowners and buyers were not willing to give up the traditional real estate agent model and changed course. In the end, Zillow decided to join rather than replace the middlemen in the real estate industry.
Polaris Battery Labs: Startup Risk Management
Authors: Walker Russell , Dilts Andrew
Published: March 2021

Polaris Battery Labs was an Oregon-based startup that provided innovation services to companies in the lithium ion battery industry. Its operating philosophy and expertise in this fast-growing industry enabled it to provide great value to its clients, but as a startup that was seeking growth the company was subject to multiple risks.

For Polaris, taking clients, developing new manufacturing capabilities to meet unproven battery technologies, and even extending credit to its clients posed real risk. Many of its clients were startups themselves and had a significant probability of failure. Others were established firms testing new and unproven battery technologies, many of which were unlikely to gain traction in the market.

The case examines how a technology-driven firm managed the risk of working with startups, claiming appropriate intellectual property, and developing a sustainable portfolio of clients.
Harley-Davidson: Rejuvenating an Iconic Brand
Authors: Roese Neal J. , Chernev Alexander
Published: March 2021

Harley-Davidson's first-ever chief marketing officer has his work cut out for him as the classic American motorcycle manufacturer seeks to curb slowing sales from aging customers. The dilemma: what to do with its less known and unprofitable Buell brand, which has a younger customer base? Which of five options continue its dual-brand strategy, double down on Buell, operate Buell as an endorsement brand, sell it, or discontinue the brand entirely will best attract younger buyers without alienating current diehard customers?