¹77Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer. / Behandling av kastrasjonsresistent metastatisk prostatakreft med [¹77Lu]PSMA-radioligand.

Background: Treatment of castration-resistant metastatic prostate cancer with [¹77Lu]PSMA radioligand. Case presentation: A man in his seventies with metastatic prostate cancer received castration therapy for four years, developing castration-resistant disease. PET/CT with [68Ga]PSMA-11 showed high uptake in metastatic lymph nodes. The patient received 7.4 GBq [¹77Lu]PSMA-I&T (Curium, Finland) as five treatments at five-week intervals. Five weeks after the first treatment, p-PSA dropped from 154 to 53 µg/L. Five weeks after the fifth treatment, p-PSA was 1.8 µg/L. [68Ga]PSMA-11 PET/CT showed significant reduction in the size of metastases, with the largest decreasing in diameter from 10 to 4 mm. Seven months after the fifth treatment, p-PSA increased to 14.3 µg/L, and [68Ga]PSMA-11 PET/ CT revealed additional skeletal metastases, while the lymph node metastases remained unchanged. Thus, the treatment had a good but temporary effect on the metastases. Interpretation: Treatment with [¹77Lu]PSMA radioligand resulted in a temporary regression of the metastases.

Miocene fossils from the southeastern Pacific shed light on the last radiation of marine crocodylians.

The evolution of crocodylians as sea dwellers remains obscure because living representatives are basically freshwater inhabitants and fossil evidence lacks crucial aspects about crocodylian occupation of marine ecosystems. New fossils from marine deposits of Peru reveal that crocodylians were habitual coastal residents of the southeastern Pacific (SEP) for approximately 14 million years within the Miocene (ca 19 to 5 Ma), an epoch including the highest global peak of marine crocodylian diversity. The assemblage of the SEP comprised two long and slender-snouted (longirostrine) taxa of the Gavialidae: the giant Piscogavialis and a new early diverging species, Sacacosuchus cordovai. Although living gavialids (Gavialis and Tomistoma) are freshwater forms, this remarkable fossil record and a suite of evolutionary morphological analyses reveal that the whole evolution of marine crocodylians pertained to the gavialids and their stem relatives (Gavialoidea). This adaptive radiation produced two longirostrine ecomorphs with dissimilar trophic roles in seawaters and involved multiple transmarine dispersals to South America and most landmasses. Marine gavialoids were shallow sea dwellers, and their Cenozoic diversification was influenced by the availability of coastal habitats. Soon after the richness peak of the Miocene, gavialoid crocodylians disappeared from the sea, probably as part of the marine megafauna extinction of the Pliocene.

Reviewing ACGME Plastic Surgery Fellowship Case Logs: Is Surgical Experience Increasing?

INTRODUCTION: Over the last decade, there has been a 32% decrease in independent plastic surgery fellowships. The growing prevalence of 6-year integrated plastic surgery residencies, duty hour restrictions, and new subspecialty training fellowships for general surgeons have changed the training experience of plastic surgery fellows. METHODS: A retrospective review of the Accreditation Council for Graduate Medical Education (ACGME) case logs for graduating fellows of independent plastic surgery fellowships in the United States was conducted from 2011 to 2019. A linear regression analysis was conducted for each case log code and category, and a 95% level of confidence was assumed (α = 0.05). RESULTS: In 2011, 141 residents from 69 programs graduated with an average of 1469.7 cases. In 2019, 84 residents from 47 programs graduated with an average of 1952 cases. Index procedures significantly increased overall during the 9 y (P < 0.001). Categorical cases increased in esthetics (P < 0.001), including facelift, browlift, blepharoplasty, and more. Categorical cases increased in reconstructive surgery (P < 0.001), including treatment of deformities of the skin, lower extremities, and trunk, nerve decompression, and hand reconstruction. In breast procedures, an increase was seen in the reduction of mammoplasty, reconstruction, and treatment of other breast deformities. In head and neck procedures, an increase was seen in resection of head and neck neoplasms and secondary cleft lip repair. Decreases in procedural numbers were seen in primary cleft lip repair and hand reconstruction by primary closure. CONCLUSIONS: Despite a 32% decline in the number of independent plastic surgery fellowships over the last 9 y, plastic surgery fellows are obtaining significantly more surgical experience, both in esthetic and reconstructive surgery.

HIV-Related Stigma and Psychological Adjustment Among Perinatally HIV-Infected Youth in Cape Town, South Africa.

The effect of chronic HIV-infection on psychological adjustment, including the impact of HIV-related stigma in perinatally HIV-infected (PHIV+) youth across Africa is largely unknown. This study examined psychological adjustment and HIV-related stigma using the Strengths and Difficulties Questionnaire (SDQ) and a 10-item stigma questionnaire in a cohort of PHIV+ youth in Cape Town, South Africa. The relationships between SDQ scores, elevated viral load, and suboptimal antiretroviral therapy (ART) adherence were also explored. Among 473 PHIV+ youth (aged 9-14 years, on ART > 6 months at enrollment), higher perceived HIV-related stigma was associated with higher scores across all adolescent and caregiver-reported SDQ difficulty subscales. Higher socioeconomic status (SES) was associated with lower scores on adolescent self- and caregiver-reported hyperactivity subscales. Higher adolescent-reported prosocial scores were associated with lower odds of self-reported suboptimal ART adherence, and higher caregiver-reported conduct scores were associated with higher odds of elevated viral load. No associations were observed between perceived HIV-related stigma and treatment outcomes. These findings highlight the potentially detrimental impact of perceived stigma on psychological adjustment in PHIV+ youth. The use of psychosocial metrics and interventions aimed at reducing illness related stigma in PHIV+ youth is also considered.

Shifting the narrative: equity, evidence, effectiveness, and innovation in the era of Ending the HIV Epidemic.

BACKGROUND: The use of evidence-based (EB) and evidence-informed (EI) criteria in determining the effectiveness of health interventions has been widely adopted by national and international agencies in their attempt to address health gaps, particularly around Ending the HIV Epidemic (EHE) initiatives. Utilization of these rigorous standards has proven critical in making progress towards achieving EHE goals, yet many communities remain unreached and underserved despite widespread adoption of EB/EI standards in public health research and practice. Although a crucial tool for innovative healthcare delivery, emphasis on the use of EB/EI parameters has created bias within the cycle of knowledge creation that favors well-resourced institutions given their capacity to meet the rigorous evaluation standards required of EB/EI science. This bias can systematically exclude institutions more aligned with community needs, such as community-based organizations and other grass-roots initiatives, which may have long-standing interventions that more effectively engage marginalized groups but do not have the capacity to meet EB/EI standards. MAIN BODY: This paper will explore the manifestation of systematic bias and research inequity in the process of identifying and assessing EB/EI HIV care interventions through the lens of a Health Resources and Services Administration funded initiative, coined the Center for Innovation and Engagement, which supports people living with HIV in the United States. An overview of the initiative is provided along with examples of how promising interventions with positive outcomes for members of marginalized communities are excluded in place of interventions that meet traditional standards of scientific rigor but are not novel or particularly innovative. Themes around academic imperialism and power hierarchies will be considered along with key barriers, lessons learned, and recommendations for promoting more equitable EB/EI research practice. CONCLUSIONS: It is crucial for entities supporting public health interventions to prioritize equity and inclusion in all stages of funding, design, and implementation. This is particularly true for conditions, such as HIV, that disproportionally impact the most marginalized. This will require approaching EB/EI research with a critical lens towards power and a willingness to dismantle historical dynamics that perpetuate inequities as a way of encouraging truly innovative solutions to support those who need it most.

Utilizing In-Hospital Fabrication to Decrease Simulation Costs.

BACKGROUND: Two restrictive factors for surgical training through simulation, are the cost of and accessibility to materials and consoles for simulation models. Commercial surgical simulation models continue to maintain high prices with a wide range of fidelity levels. We believe that by utilizing in-house fabrication, these barriers can be decreased while maintaining and even improving the functionality of surgical simulation models as well as increase their individualization and customization. METHODS: By using a combination of digital and manual fabrication techniques such as 3D printing and basic mold making methods, we were able to create models equivalent to current commercial products by utilizing the first of its kind MakerHEALTH space and collaborating with our surgical simulation staff. We then compared our research and development, start-up, materials, operational, and labor costs to buying comparable commercial models with the simulation usage rates of our institution. RESULTS: We were able to decrease the costs of a 6 model simulation sample set (appendectomy, cholecystectomy, common bile duct exploration, ventral hernia, chest tube insertion, and suture pads) at our institution from $99,646.60 to $13,817.21 for a medical student laborer, $14,500.56 for a surgical resident laborer, $15,321.08 for a simulation staff laborer, and $18,984.48 for an attending physician laborer. CONCLUSION: We describe successful approaches for the creation of cost-effective and modular simulation models with the aim of decreasing the barriers to entry and improving surgical training and skills. These techniques make it financially feasible for learners to train during larger faculty-led workshops and on an individual basis, allowing for access to simulation at any time or place.

Tele-education assisted mentorship in surgery (TEAMS).

Tele-education assisted mentorship in surgery (TEAMS) is a novel methodology for surgical skills training with remote, hands-on, high-fidelity, and low-cost simulation-based education and one-to-one mentorship with longitudinal assessments. We review the background, methodology, and our experience with implementing TEAMS as an adjunct to traditional methods of surgical education and mentorship.

[Reference values for SPPB in people over 60 years of age in the Basque Country]. / Valores de referencia del SPPB en personas mayores de 60 años en el País Vasco.

PURPOSE: To provide reference values of Short Physical Performance Battery (SPPB) in adults and older adults in the Basque Country by identifying cut-off points for measuring fragility and comparing the values with other populations in Spain. LOCATION: Bilbao capital, Basque Country (Spain). PARTICIPANTS: 1923 people over 60 years old included in the Health Program for the Elderly of the City of Bilbao participated in the study. The PA program was delivered twice a week for a minimum of 12 weeks, with 50-minute sessions. MAIN MEASUREMENTS: Participants were evaluated with the SPPB, which assesses balance (PE), gait speed test (PM) and chair stand test (PS). Based on the results obtained from all tests, the functionality of the participants was identified as: severe (0-4 points), moderate (4-6 points), mild (7-9 points) and minimal (10-12 points) limitation. RESULTS: Mean age was 77.9 (5.6) years, 87.9% were women and 12.1% were men. The SPPB showed significant differences in age (p = 0.000) and gender (p = 0.005). In addition, a comparison was made with a similar population: 70-75 years = 0.6 (Cohen's d), 76-79 years = 0.98 (Cohen's d), and >80 years = 0.98 (Cohen's d). CONCLUSIONS: The present study indicates normative values for SPPB. People's functionality decreases, as they get older. Despite the current findings available to health professionals for more effective detection of fragility, many of them have not yet been translated into clinical practice.

Development of a Low-cost, High-fidelity Skin Model for Suturing.

BACKGROUND: In a survey of students at our institution, suturing was the most desired workshop for simulation; however, cost, quality, and availability of skin pads is often prohibitive for suturing workshops. In-hospital fabrication may be utilized to manufacture noncommercial, high-fidelity, and low-cost simulation models. We describe the production, value, and face validation of our simulated skin model. MATERIALS AND METHODS: Using an in-hospital fabrication laboratory, we have developed a model for skin and subcutaneous tissue. Our model uses a variety of commercially available materials to simulate the epidermis, dermis, subcutaneous fat, fascia, and muscle. A cost analysis was performed by comparing it with other commonly used commercial skin models. Expert surgeons assessed the material characteristics, durability, and overall quality of our model in comparison with other commercial models. RESULTS: The materials cost of our novel skin pad model was 30.9% of the mean cost of five different commonly used foam and silicone-based commercial skin models. This low-cost model is more durable than the commercial models, does not require skin pad holders, and is of higher fidelity than the commercial products. In addition to skin closure, our model may be used to simulate fascial closure or fasciotomy. CONCLUSIONS: Model creation using in-hospital workspaces is an effective strategy to decrease cost while improving quality of surgical simulation. Our methods for creation of an inexpensive and high-fidelity skin pad may be purposed for several soft tissue models.

Efavirenz is associated with altered fronto-striatal function in HIV+ adolescents.

Neurotoxicity associated with the antiretroviral efavirenz (EFV) has been documented in HIV-infected adults, but there are no data on the impact of EFV on brain function in adolescents. We investigated potential alterations in fronto-striatal function associated with EFV use in adolescents. A total of 86 adolescents underwent a Stop Signal Anticipation Task (SSAT) during functional MRI (fMRI), 39 HIV+ adolescents receiving EFV, 27 HIV+ adolescents on antiretroviral therapy without EFV (matched on age, gender, education, CD4 cell count and HIV viral load) and 20 HIV- matched controls (matched on age and gender). The task required participants to give timed GO responses with occasional STOP signals at fixed probabilities. Reactive inhibition was modelled as a correct STOP response and proactive inhibition was modelled after response slowing as the STOP probability increases. A priori mask-based regions associated with reactive and proactive inhibition were entered into two respective multivariate ANOVAs. The EFV treatment group showed significantly blunted proactive inhibitory behavioural responses compared to HIV+ adolescents not receiving EFV. There was no difference in reactive inhibition between treatment groups. We also demonstrated a significant effect of EFV treatment on BOLD signal in proactive inhibition regions. There was no difference in regions involved in reactive inhibition. We found no differences between adolescents not receiving EFV and HIV- controls, showing that functional and behavioural differences were unique to the EFV group. Here, we demonstrate for the first time a potential adverse impact of EFV on higher cortical function in young HIV+ adolescents.

Natural Products from Photorhabdus and Other Entomopathogenic Bacteria.

Although the first natural products (NP) from Photorhabdus and Xenorhabdus bacteria have been known now for almost 30 years, a huge variety of new compounds have been identified in the last 5-10 years, mainly due to the application of modern mass spectrometry. Additionally, application of molecular methods that allow the activation of NP production in several different strains as well as efficient heterologous expression methods have led to the production and validation of many new compounds. In this chapter we discuss the benefit of using Photorhabdus as a model system for microbial chemical ecology. We also examine non-ribosomal peptide synthetases as the most important pathway for NP production. Finally, we discuss the origin and function of all currently known NPs and the development of the molecular and chemical tools used to identify these NPs faster.

Factors influencing organic carbon accumulation in mangrove ecosystems.

There is growing interest in the capacity of mangrove ecosystems to sequester and store 'blue carbon'. Here, we provide a synthesis of 66 dated sediment cores with previously calculated carbon accumulation rates in mangrove ecosystems to assess the effects of environmental and anthropogenic pressures. Conserved sedimentary environments were found to be within the range of the current global average for sediment accretion (approx. 2.5 mm yr-1) and carbon accumulation (approx. 160 g m-2 yr-1). Moreover, similar sediment accretion and carbon accumulation rates were found between mixed and monotypic mangrove forests, however higher mean and median values were noted from within the forest as compared to adjacent areas such as mudflats. The carbon accumulation within conserved environments was up to fourfold higher than in degraded or deforested environments but threefold lower than those impacted by domestic or aquaculture effluents (more than 900 g m-2 yr-1) and twofold lower than those impacted by storms and flooding (more than 500 g m-2 yr-1). These results suggest that depending on the type of impact, the blue carbon accumulation capacity of mangrove ecosystems may become substantially modified.

Lung transplantation delays gastric motility in patients without prior gastrointestinal surgery-A single-center experience of 412 consecutive patients.

PURPOSE: To examine the impact of lung transplantation on gastric motility. METHODS: Adult recipients at a large, single center, who were retrospectively evaluated with solid gastric emptying (SGE) study post-lung transplantation, but had no history of gastrointestinal intervention (ie, pyloroplasty or fundoplication), were selected between June 2005 and August 2013. Multivariable logistic regression was performed to determine risk factors associated with delayed gastric emptying (DGE) after transplantation. RESULTS: Delayed gastric emptying (DGE) was noted in 236 patients (57%) after transplantation. On multivariable logistic regression, an underlining diagnosis of cystic fibrosis (CF)/bronchiectasis (adjusted odds ratio [AOR] 3.26, P < .01) was a significant risk factor in predicting DGE after lung transplantation. There was no survival difference between patients with postoperative DGE vs those without (log-rank test P = .53). CONCLUSIONS: Delayed gastric emptying is very common following lung transplantation, occurring in over half of all lung transplant recipients with increased prevalence in patients with CF. The association with cystic fibrosis could be secondary to extra-pulmonary manifestations of the underlying disease or indicative of increased intraoperative vagal nerve injury. We speculate that DGE may play a substantial role in the increased reflux-induced allograft injury seen after lung transplantation. Further prospective studies are needed to validate this hypothesis.

Subtotal cholecystectomy for the hostile gallbladder: failure to control the cystic duct results in significant morbidity.

BACKGROUND: Outcomes following the inability to control the cystic duct due to a hostile triangle of Calot during cholecystectomy remain unknown. The purpose of this study was to analyze the safety and efficacy of subtotal cholecystectomy, with attention to the necessity for secondary interventions. METHODS: Sixteen thousand five hundred ninety six cholecystectomies from January 2002 to August 2014 were reviewed, identifying patients managed with subtotal cholecystectomy, defined as the inability to isolate/transect the cystic duct. After propensity matching, we investigated surgical indications, perioperative outcomes, and the necessity for secondary ERCP, percutaneous drainage, and completion cholecystectomy. RESULTS: 65 (0.39%) patients underwent subtotal cholecystectomy; 54 (83.1%) began laparoscopically, of which 30 (55.6%) required conversion to laparotomy. Subtotal cholecystectomy, performed more frequently for acute cholecystitis (70.8% vs 34.6%), was associated with extended hospitalizations (4 d vs 2 d) and frequent surgical site infections (20% vs 4.6%). 25 (38.5%) subtotal cholecystectomy patients required ≥1 secondary intervention, and compared to standard cholecystectomy, underwent higher rates postoperative ERCP (30.8% vs 5.4%), percutaneous drainage (9.2% vs 1.5%), and completion cholecystectomy (6.2% vs 0%) [all P < 0.05]. DISCUSSION: Subtotal cholecystectomy fails to control the cystic duct, resulting in significant morbidity. Most do not require completion cholecystectomy; however, patients demand close observation and, frequently, secondary interventions.

Solid-Phase Enrichment and Analysis of Azide-Labeled Natural Products: Fishing Downstream of Biochemical Pathways.

Many methods have been devised over the decades to trace precursors of specific molecules in cellular environments as, for example, in biosynthesis studies. The advent of click chemistry has facilitated the powerful combination of tracing and at the same time sieving the highly complex metabolome for compounds derived from simple or complex starting materials, especially when the click reaction takes place on a solid support. While the principle of solid-phase click reactions has already been successfully applied for selective protein and peptide enrichment, the successful enrichment of much smaller primary and secondary metabolites, showing great structural diversity and undergoing many different biosynthetic steps, has seen only little development. For bacterial secondary metabolism, a far broader tolerance for "clickable" precursors was observed than in ribosomal proteinogenesis, thus making this method a surprisingly valuable tool for the tracking and discovery of compounds within the cellular biochemical network. The implementation of this method has led to the identification of several new compounds from the bacterial genera Photorhabdus and Xenorhabdus, clearly proving its power.

[Epidemiological profile of traumatic brain injury at the Dr. Rafael A. Calderón Guardia Hospital, Neurosurgery Department, during the period from 2007 to 2012]. / Perfil epidemiológico del traumatismo craneoencefálico en el Servicio de Neurocirugía del Hospital Dr. Rafael A. Calderón Guardia durante el período 2007 a 2012.

OBJECTIVE: To determine the epidemiological profile of the patients who suffered traumatic brain injury (TBI) and were treated at the Dr. Rafael A. Calderón Guardia Hospital (HCG) Neurosurgery department, during the period from 2007 to 2012. MATERIAL AND METHODS: An observational, descriptive, retrospective and cross section study was performed on all the patients with TBI and who were admitted to the emergency room of the HCG during the period 2007 to 2012. There were a total of 721 cases, of which 566 records were obtained of patients who had the variables established in this study, excluding those with incomplete or inconsistent information. RESULTS: The present study established the epidemiological profile of the TBI in the population seen during the period 2007 to 2012 at the HCG. It was determined that the male sex made up the majority of the cases were male, with mean age of 46 years. The mortality rate was 12.69% (n=69). Car accidents were the most frequent cause of TBI (n=259 persons) in the age group of 25 to 44 years, followed by falls (n=174). It was observed that the majority were farmers, followed by students, and then construction workers. No chronic illnesses were recorded in 71.6% of the medical charts. No alcohol or other drugs were reported in 74.9% of the cases, while there was evidence of the presence of alcohol recorded in 22.8%. The clinical and laboratory parameters that had statistical significance (P<.05) were GCS equal to less than 8 (P=.035), presence of mydriasis (P=.00), deviation of the LM (P=.006), cranial fracture (P=.04), lack of endotracheal intubation on admission (P=.007), prolonged PT (P=.04), prolonged PTT (P=.025), and MAP<60 (P=.002). The most frequent surgical procedure in the study population was craniotomy with hematoma drainage alone or associated with some other procedure (esquillectomy or monitoring of PIC) (n=298). CONCLUSIONS: There is great difficulty in determining the epidemiology of TBI worldwide, due to the lack of standardisation of the international studies. From the present study, it can be concluded that the population that mainly suffers from this type of lesion are adults under 45 years old, with car accidents being the main cause of these lesions (45.8%) in combination with alcohol consumption. Also, the consequences of such are aggravated when the victims present with chronic diseases such as, systemic arterial hypertension and mellitus diabetes. As regards the post-traumatic indicators directly related to a poor outcome, it was determined that a GCS score equal to or less than 8, a mean blood pressure less than 60, the prolongation of the coagulation times, the presence of mydriasis, and skull fractures, have a direct association with the negative or fatal outcome for the victim.

"Click Chemistry" for the Simple Determination of Fatty-Acid Uptake and Degradation: Revising the Role of Fatty-Acid Transporters.

Fatty acids (FAs) have numerous functions in all living organisms, ranging from structural roles and energy production to the biosynthesis of secondary metabolites. Because of the high energy content of exogenous FAs, their acquisition is central of metabolism, and several biological systems are known, although their precise roles are not yet entirely clear. We investigated the roles of FadD (CoA ligase) and FadL (FA transporter) in different bacterial strains by using an improved version of click-chemistry-assisted labelling of azido-FAs. The high sensitivity of this method allows a direct and precise assessment of FA metabolism, and is thus far better suited than growth experiments. Our results show that although FA activation is indeed essential for FA degradation, their transport can be independent of transporters like FadL.

Gangrenous cholecystitis: a contemporary review.

BACKGROUND: Despite the established superiority of laparoscopic cholecystectomy (LC) for acute cholecystitis, gangrenous cholecystitis (GC) is commonly treated with open cholecystectomy (OC). This study aimed to characterize outcomes of GC in the modern era and between LC or OC surgical approach. MATERIALS AND METHODS: Patients with a diagnosis of GC were identified using the 2005-2011 National Surgical Quality Improvement Project Participant User File. Baseline patient and operative characteristics and 30-d outcomes were established for all patients. Patients were stratified by surgical approach (LC or OC), and groups were propensity matched with a nearest-neighbor matching algorithm. Primary outcomes were 30-d mortality and any 30-d complication. A nonparsimonious multiple logistic regression model was used in the matched subset to adjust for patient comorbidities, demographics, and laboratory values. RESULTS: A total of 141,970 cholecystectomies were identified with 7017 having a diagnosis of GC. Overall 30-d mortality for the entire cohort was 0.8% (n = 239) and overall 30-d complication rate was 8.0% (n = 2485). For GC patients, the 30-d mortality was 1.2% (n = 84) and overall complication rate was 10.8% (n = 761). The multivariate logistic regression model demonstrated a significant decrease in overall (odds ratio = 0.46; P < 0.001) complication rates for LC patients but did not reveal a significant difference in 30-d mortality (odds ratio = 0.59; P = 0.12). CONCLUSIONS: GC is associated with increased morbidity and mortality compared with that of acute cholecystitis. A LC approach is a safe option for patients with GC and is associated with decreased 30-d morbidity. Although LC should be used when possible for GC to minimize postoperative complications, OC should not be avoided if necessary to ensure patient safety.