Erythrocytosis Is Rare With Exogenous Testosterone in Gender-Affirming Hormone Therapy.

CONTEXT: Studies have found a variable incidence of erythrocytosis among people using testosterone as part of gender-affirming hormone therapy (GAHT). OBJECTIVE: To examine the effect of using exogenous testosterone as GAHT on hematocrit in a large North American cohort. METHODS: We conducted a cross-sectional analysis of testosterone and hematocrit laboratory values in 6670 patients who were prescribed testosterone through Plume, a national provider of GAHT. The prevalence of erythrocytosis, the mean hematocrit at predetermined testosterone thresholds and with varying routes of testosterone administration were assessed. RESULTS: Among 6670 individuals, 560 (8.4%) had a hematocrit ≥50%, 182 ≥ 52% (2.7%), and 60 ≥ 54% (0.9%). There was significant variation (P < .001) in hematocrit between different clinically relevant testosterone thresholds (T < 50 vs T 50-299 vs T 300-999 vs T ≥ 1000 ng/dL) and when comparing serum testosterone in increments of 50 ng/dL within the target range for males (300-1000 ng/dL) (P < .001). Mean hematocrit ranged from 41.84% (T < 50 ng/dL) to 45.68% (T 900-949 ng/dL). Patients on intramuscular testosterone had a higher mean hematocrit than those on transdermal testosterone (44.96% vs 43.41%, P < .001). Both route of administration (P < .001) and testosterone level (P < .001) had statistically significant associations with hematocrit when controlling for each other. CONCLUSION: While the magnitude of change in hematocrit with serum level and route of administration of testosterone was statistically significant, the absolute levels were within the normal range, unlikely to be clinically meaningful. These findings, along with the low prevalence of erythrocytosis, should help allay concerns about the use of testosterone as GAHT.

Laparoscopic Paraesophageal Hernia (PEH) Repair, Roux-en-Y Gastric Bypass, and Per Oral Endoscopic Myotomy (POEM) in a Patient with Achalasia After Sleeve Gastrectomy.

BACKGROUND: GERD and Achalasia are two known complications after sleeve gastrectomy. Treatment towards each of these complications varies and requires a tailored approach. METHODS: We present a 55-year-old female with class II obesity and a previous history of sleeve gastrectomy who developed significant gastroesophageal reflux disease refractory to medical management. After a covid infection in fall of 2020, she began to report new symptoms of dysphagia that progressed from solids to liquids. She underwent extensive workup including upper endoscopy, upper GI barium swallow, manometry, pH impedence, and EndoFlip leading to a diagnosis of Achalasia type II as well as a paraesophageal hernia. RESULTS: Given these findings, she underwent a combined paraesophageal hernia repair with conversion of sleeve gastrectomy to Roux-en-Y gastric diversion and an intra-operative peroral endoscopic myotomy. Intraoperatively, she was noted to have significant lower abdominal adhesions leading to performing the Roux-en-Y reconstruction through a supramesocolic defect in a retrocolic fashion. CONCLUSIONS: While the development of heartburn and achalasia after sleeve gastrectomy is rare, it requires interventions dedicated towards each etiology. This case demonstrates treatment of both these symptoms is feasible in a single operation.

Small Bowel Follow-Through: Treatment for Small Bowel Obstruction or Delaying the Inevitable?

BACKGROUND: Over 400,000 patients are admitted annually for small bowel obstruction (SBO), of which 20-40% require operative intervention, representing more than 2.3 billion dollars in healthcare expenses. Recurrence of SBO increases with a longer duration of follow-up with up to 15-20% recurrence rates within a five-year period. Small bowel follow-through (SBFT) consisting of serial X-rays with oral contrast has been shown to decrease overall length of stay (LOS) in patients with adhesive SBO. The aim of this study is to determine if SBFT administered to patients with SBO decreases 30-day and up to five-year readmission rates secondary to recurrent SBO. METHODS: The institutional review board (IRB) approved a single institution retrospective study from 2010 to 2020 that included a total of 742 patients. These patients were organized into groups of those who received the SBFT <24 hours after admission (n=40), those who received the SBFT >24 hours (n=198), and the third group of patients who did not receive the SBFT (n=658). Readmission rates <30 days, 70 years along with BMI <25, 25-29.9, 30-34.9, 35-39.9, >40, as well as the number of intraabdominal surgeries, gender, and need for operative intervention during the admission were evaluated to assess for any associations with recurrence. Readmission within 30 days and up to five years were compared. RESULTS: There were no significant differences in recurrence rates between groups with SBFT <24 hours (p=0.338) or SBFT >24 hours (p=0.889) when compared to the no SBFT group. There was nearly a 48% chance of readmission for another episode of an SBO for patients who did not undergo an operative intervention. While patients who underwent operative intervention had around a 29% chance of having a subsequent episode of an SBO. This is consistent with a statistically significant decrease in one-year (p=0.027) recurrences in patients who underwent operative intervention. CONCLUSION: There was no significant difference in recurrences with gender, most BMI groups, or in groups who underwent an SBFT. Operative intervention is associated with a statistically significant decrease in recurrence rates of SBO within one year of presentation.

SAGES white paper on the current state of community practice surgeons: re-discovering the value of our community practice surgeons.

BACKGROUND: The Community Practice (CP) surgeon is the first point of access to surgical care globally and performs the majority of procedures in the USA. CP surgeons include those of various practice models, locations and communities, education and training, and much more. It is a diverse group that drives quality, access to care, research, and innovation. The SAGES CP Committee was formed to better define the role and highlight the contribution of the CP surgeon, as well as advocate for the position of CP surgeons in our society. METHODS: In 2018, a survey was distributed to the SAGES membership asking members to self-identify as either a Community Surgeon or Academic Surgeon. RESULTS: The majority (71%) of SAGES members surveyed self-identified as "Community Surgeons." This was in stark contrast to the distribution of Community versus Academic Surgeons in SAGES leadership (25% versus 75%, respectively). CONCLUSION: By better defining the characteristics and role of the CP, SAGES will be better informed on how to effectively engage with this large group within the society and increase its representation within the leadership. The CP Committee met on a biannual basis over a period of two years focusing on assessing their role in the SAGES organization. The committee members created the following initial goals: (1) define in a broad sense the characteristics of a CP Surgeon, (2) discuss and characterize the value of the CP surgeons, (3) highlight past and future areas of contributions of the group, and (4) delineate ways to engage and represent this subgroup. This manuscript is a culmination of the work of this committee while also serving as a way to support the initiatives and direction of SAGES leadership.

Use of Theoretical Frameworks in the Development and Testing of Palliative Care Interventions.

CONTEXT: Palliative care (PC) research has grown over the last 20 years. Yet, the causal components and pathways of PC interventions remain unclear. OBJECTIVES: To document the prevalence and application of theoretical frameworks in developing and testing PC interventions. METHODS: We conducted a secondary analysis of previously published systematic reviews of PC randomized clinical trials. Trials were evaluated for explicit mention of a theoretical framework, process or delivery model, or clinical practice guideline that supported the development of the intervention. We used a structured data extraction form to document study population, outcomes, and whether and how authors used a theoretical framework, process/delivery model, or clinical practice guideline. We applied an adapted coding scheme to evaluate use of theoretical frameworks. RESULTS: We reviewed 85 PC trials conducted between 1984 and 2021. Thirty-eight percent (n = 32) of trials explicitly mentioned a theoretical framework, process or delivery model, or clinical practice guideline as a foundation for the intervention design. Only nine trials included a theoretical framework, while the remaining 23 cited a process/delivery model or clinical practice guideline. CONCLUSION: Most PC trials do not cite a theoretical foundation for their intervention design. Future work should focus on developing and validating new theoretical frameworks and modifying existing theories and models to better explain the mechanisms of the variety of PC interventions.

Early Use of Small Bowel Follow Through Reduces Stay and Cost in Small Bowel Obstructions.

Background According to the Nationwide Inpatient Sample in 2011, nearly 1,500,000 admissions with over 300,000 laparotomies were performed for adhesion-related small bowel obstructions (SBOs). Small bowel follow through (SBFT) consists of serial X-rays with oral Gastrografin contrast that can diagnose obstructions requiring operative intervention. Furthermore, the contrast has a therapeutic osmotic effect which may promote transit and resolve an SBO. The aim of the study was to determine if early SBFT administration to patients with SBO decreases length of stay (LOS), hospital costs, and can identify patients who will fail non-operative management (NOM). Methodology This is a single institution retrospective study conducted from 2010 to 2019 with a total of 476 patients. We divided patients into three groups: SBFT within <24 hours of admission (n = 40), SBFT >24 hours after admission (n = 198), and did not receive SBFT (n = 238). We compared the overall LOS, hospital costs, and time from SBFT to the operating room using an analysis of variance. Results LOS significantly differed between groups with SBFT within ≤24 hours having an average LOS of 6.95 days compared to 10.65 days in the SBFT after >24 hours and 11.75 days in the no SBFT group (p = 0.005). Median time to the operating room in patients receiving SBFT was one day, which was significantly shorter than a median time of four days for no SBFT group (p = <0.05). Decreased LOS by 4.8 days equated to saving $8,657 per patient. Conclusions SBFT administered within 24 hours decreases LOS, overall costs, and time to operating room in patients who fail NOM.

CARDIOVASCULAR HEALTH MAINTENANCE IN AGING INDIVIDUALS: THE IMPLICATIONS FOR TRANSGENDER MEN AND WOMEN ON HORMONE THERAPY.

OBJECTIVE: To review screening guidelines for cardiometabolic disease in aging patients and review literature describing the effect of hormone therapy (HT) on several key cardiometabolic processes to inform providers caring for older transgender individuals. METHODS: A traditional literature review was performed using PubMed and Google Scholar databases. RESULTS: The risk of cardiovascular disease increases with age. Exogenous sex hormones may interact with hormone-dependent metabolic pathways and affect some biochemical assays, but they do not necessarily impact clinical outcomes. While long-term HT is associated with an increased risk of some adverse cardiovascular outcomes, modern treatment regimens minimize this risk. CONCLUSION: Screening for cardiometabolic derangements and risk reduction are important for all aging individuals. Currently, there is insufficient evidence to propose separate screening recommendations for transgender individuals on long-term HT. Aging transgender men and women should be monitored for cardiovascular disease in much the same way as their cisgender counterparts.

An Unusual Cause of Hemorrhagic Cystitis in a Teenager With Medulloblastoma.

Hemorrhagic cystitis is a life-threatening condition in which the transitional epithelium and blood vessels of the bladder necrose leading to severe hematuria, abdominal pain, and voiding lower urinary tract symptoms. Etiology includes chemotherapy (cyclophosphamide, ifosfamide, busulfan), radiotherapy, or infectious agents. We present a pediatric case of a 15-year-old boy with medulloblastoma who developed hemorrhagic cystitis following cisplatin chemotherapy. All other causes were ruled out and it is therefore likely that the agent, in this case, was cisplatin, which has never had hemorrhagic cystitis reported as a side effect. We also suggest a mechanism for urothelial injury centered around OCT-2 receptors.

Gallbladder Nonvisualization in Cholecystectomy: A Factor for Conversion.

BACKGROUND AND OBJECTIVES: Many risk factors have been identified in minimally invasive cholecystectomies that lead to higher complications and conversion rates. No study that we encountered looked at nonvisualization of the gallbladder (GB) during surgery as a risk factor. We hypothesized that nonvisualization was associated with an increased risk of complications and could be an early intraoperative identifier of a higher risk procedure. Recognizing this could allow surgeons to be aware of potential risks and to be more likely to convert to open for the safety of the patient. METHODS: We looked at minimally invasive cholecystectomies performed at our institution from January 2015 through April 2016 and had the performing resident fill out a survey after the surgery. Outcomes were conversion rates, intraoperative complications, and blood loss and were analyzed via Pearson χ2 test or Mann-Whitney U test. RESULTS: The primary outcome showed a conversion rate of 37% in nonvisualized GBs versus 0% in visualized (P = .001). Secondary outcomes showed significant differences in GB perforations (74% vs 13%, P = .001), omental vessel bleeding (16% vs. 0%, P = .005), and EBL (46 mL vs 29 mL, P = .001). CONCLUSIONS: Intraoperative nonvisualization of the GB after adequate positioning caused significantly increased risk of intraoperative complications and conversion. This knowledge could be useful during intraoperative assessment, to decide whether a case should be continued as a minimally invasive procedure or converted early to help reduce risk to the patient. Further randomized controlled studies should be performed to further demonstrate the value of this assessment.

Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries.

We recently identified sphingosine-1-phosphate (S1P) signaling and the cystic fibrosis transmembrane conductance regulator (CFTR) as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i) express critical S1P signaling elements, (ii) constrict in response to S1P and (iii) lose myogenic responsiveness following S1P receptor antagonism (JTE013). However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.

Participants with schizophrenia retain the information necessary for informed consent during clinical trials.

OBJECTIVE: Cognitive impairment is a characteristic of schizophrenia. This impairment may affect the retention of information required for ongoing knowledgeable participation in clinical trials. This study monitored retention of study-related knowledge-including assessment of therapeutic misconception-in people with stable, DSM-IV schizophrenia during participation in placebo-controlled clinical trials of adjunctive agents. Stability was defined as being on an antipsychotic with no change in medication or dose over the previous 4 weeks. METHOD: This longitudinal study assessed retention of clinical trial-related consent information. Individuals enrolling in 1 of 8 clinical trials were approached for participation. Participants came from research clinics and community mental health centers. At baseline, clinical trial consent forms were reviewed and study knowledge assessed. Participants were randomized to follow-up assessments at weeks 1, 4, and 8; weeks 4 and 8; or at week 8 only. Clinical trial consent forms were not rereviewed at any follow-up visit. RESULTS: Fifty-nine participants were enrolled; analysis included 52 participants with at least 1 follow-up visit. Study knowledge did not decrease meaningfully in any group. Therapeutic misconception was not observed in participants during the study. The group assessed most frequently demonstrated significant improvement over baseline (t44 = 3.43, P = .001). Retention of study knowledge was not related to symptoms but had a weak correlation with cognitive capacity (R = 0.28, P = .07). Performance did not differ between participants from research clinics and those from community mental health centers. CONCLUSIONS: Clinically stable people with schizophrenia enrolling in a placebo-controlled adjunctive medication study, once determined to have capacity to consent to a clinical trial, retained appropriate study knowledge for at least 8 weeks. In the absence of a specific reason to suspect a loss of decisional capacity, there appears to be no need to routinely reevaluate participants during this type of clinical trial.

Characteristics of rare disease marketing applications associated with FDA product approvals 2006-2010.

New drug and biologic product marketing applications submitted to FDA's Center for Drug Evaluation and Research (CDER) between 2006 and 2010 were analyzed to identify rare disease application characteristics associated with higher approval rates. The results show that approval rates were similar for rare and common disease applications. Larger company size, prior regulatory experience and priority review designation were associated with higher approval rates. The study findings show that rare disease product development is feasible, and increased interactions between product developers and FDA in early investigational phases can facilitate product development.