Discovery of antiphage systems in the lactococcal plasmidome.

Until the late 2000s, lactococci substantially contributed to the discovery of various plasmid-borne phage defence systems, rendering these bacteria an excellent antiphage discovery resource. Recently, there has been a resurgence of interest in identifying novel antiphage systems in lactic acid bacteria owing to recent reports of so-called 'defence islands' in diverse bacterial genera. Here, 321 plasmid sequences from 53 lactococcal strains were scrutinized for the presence of antiphage systems. Systematic evaluation of 198 candidates facilitated the discovery of seven not previously described antiphage systems, as well as five systems, of which homologues had been described in other bacteria. All described systems confer resistance against the most prevalent lactococcal phages, and act post phage DNA injection, while all except one behave like abortive infection systems. Structure and domain predictions provided insights into their mechanism of action and allow grouping of several genetically distinct systems. Although rare within our plasmid collection, homologues of the seven novel systems appear to be widespread among bacteria. This study highlights plasmids as a rich repository of as yet undiscovered antiphage systems.

The Princeton IV Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease.

The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative symposium dedicated to optimizing sexual function and preserving cardiovascular health. The Fourth Princeton Consensus Conference was convened on March 10-11, 2023, at the Huntington Medical Research Institutes in Pasadena, California. Princeton panels I to III addressed the clinical management of men with erectile dysfunction (ED) who also had cardiovascular disease. Thirteen years since Princeton III, Princeton IV builds on previous foundations in several key areas. Mounting evidence supports the need for providers to treat men with ED as being at risk for cardiac events until proven otherwise. Algorithms for the diagnosis and treatment of ED are updated with new recommendations for coronary artery calcium scoring for advanced cardiovascular risk stratification. Optimization of oral phosphodiesterase type 5 inhibitors in the treatment of men with ED and cardiovascular disease is thoroughly explored, including recent evidence of potential cardioprotective effects of these drugs.

Predicting Recurrent Deficiency and Suboptimal Monitoring of Thiamin Deficiency in Patients with Metabolic and Bariatric Surgery.

INTRODUCTION: Vitamin B1 (thiamine) deficiency (TD) after metabolic and bariatric surgery (MBS) is often insidious and, if unrecognized, can lead to irreversible damage or death. As TD symptoms are vague and overlap with other disorders, we aim to identify predictors of recurrent TD and failure to collect B1 labs. METHODS: We analyzed a large sample of data from patients with MBS (n = 878) to identify potential predictors of TD risk. We modeled recurrent TD and failure to collect B1 labs using classical statistical and machine learning (ML) techniques. RESULTS: We identified clusters of labs associated with increased risk of recurrent TD: micronutrient deficiencies, abnormal blood indices, malnutrition, and fluctuating electrolyte levels (aIRR range: 1.62-4.68). Additionally, demographic variables associated with lower socioeconomic status were predictive of recurrent TD. ML models predicting characteristics associated with failure to collect B1 labs achieved 75-81% accuracy, indicating that clinicians may fail to match symptoms with the underlying condition. CONCLUSIONS: Our analysis suggests that both clinical and social factors can increase the risk of life-threatening TD episodes in some MBS patients. Identifying these indicators can help with diagnosis and treatment.

Safety of topical sildenafil cream, 3.6% in a randomized, placebo-controlled trial for the treatment of female sexual arousal disorder.

BACKGROUND: There are currently no Food and Drug Administration-approved treatments for female sexual arousal disorder (FSAD), which is physiologically analogous to male erectile dysfunction. AIMS: The study sought to test the systemic and local genital safety of topical sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD and their sexual partners over a 12-week treatment period. METHODS: This was a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream among healthy premenopausal women with FSAD. Safety was assessed by the frequency and incidence of treatment-emergent adverse events (TEAEs) among participants and their sexual partners. Participants recorded the incidence of TEAEs in a daily eDiary (electronic diary). Sexual partners were contacted within 72 hours of each sexual event in which investigational product was used. All participants used placebo cream for 1 month, during a single-blind run-in period, and then if eligible, were randomized 1:1 to sildenafil cream or placebo cream. Participants used their assigned investigational product over a 12-week double-blind dosing period. They attended monthly follow-up visits, in which their eDiary TEAE data were reviewed by the study staff and graded for severity and relationship to study product. OUTCOMES: The frequency and incidence of TEAEs among participants and their sexual partners. RESULTS: During the 12-week double-blind dosing period, there were 78 TEAEs reported by 29 of 99 sildenafil-assigned participants and 65 TEAEs reported by 28 of 94 placebo-assigned participants (P = .76). All TEAEs were mild or moderate in severity. The most common treatment-related TEAE among active and placebo-assigned participants was application site discomfort. There were no differences in the number of treatment-related TEAEs among sildenafil cream vs placebo cream users (P > .99). Four sildenafil cream participants and 3 placebo cream participants discontinued the study due to TEAEs involving application site discomfort (P > .99). There were 9 TEAEs reported by 7 of 91 sexual partners exposed to sildenafil cream vs 4 TEAEs reported by 4 of 84 sexual partners exposed to placebo cream (P = .54). CLINICAL IMPLICATIONS: These data support further clinical development of topical sildenafil cream for the treatment of FSAD. STRENGTHS AND LIMITATIONS: Safety was assessed among participants and their sexual partners after 1357 and 1160 sexual experiences in which sildenafil cream or placebo cream were used, respectively. The phase 2b study was powered for the primary objectives of efficacy, rather than safety. CONCLUSION: These data demonstrate that topically applied sildenafil cream was safe and well tolerated by exposed users and their sexual partners.

Safety of elective enteral access in elderly patients: a comparative analysis of perioperative risk.

BACKGROUND: Elderly patients can experience torpid hospitalization that is often characterized by malnutrition. In this setting, enteral feeding may facilitate improvement in nutritional status. This study aimed to compare the perioperative outcomes between elderly (age of ≥65 years old) and nonelderly (age of <65 years old) patients undergoing elective enteral access placement. METHODS: Adult patients who underwent enteral access procedures between 2018 and 2020 at a tertiary care facility were retrospectively reviewed. Differences in baseline characteristics between nonelderly and elderly patients were adjusted using entropy-balanced weights. Subsequently, multivariate logistic and linear regression models were developed to evaluate the association between elderly status and outcomes of interest. RESULTS: Overall, 914 patients with enteral access met the inclusion criteria, of whom 471 (51.5%) were elderly. Elderly patients more commonly received percutaneous gastrostomy and had a higher burden of comorbidities as measured using the Charlson Comorbidity Index than nonelderly patients. Multivariate risk adjustment generated a strongly balanced distribution of baseline covariates between patient groups. After adjustment, despite no significant association with inhospital mortality, reoperation, or time to feeding goals, elderly status was linked to an approximately 8-day reduction in length of stay (95% CI, -14.28 to -2.30; P = .007) and significantly lower odds of total parenteral nutrition (adjusted odds ratio [AOR], 0.59; 95% CI, 0.37-0.94; P = .026) and nonelective readmission (AOR, 0.65; 95% CI, 0.49-0.86; P = .003). In addition, elderly status was associated with significantly greater odds of nonhome discharge (AOR, 1.58; 95% CI, 1.17-2.13; P = .003). CONCLUSION: Despite having more comorbidities than their nonelderly counterparts, elderly patients experienced favorable nutritional and perioperative outcomes after enteral access placement.

Learning curve of laparoscopic appendectomy in a low-resource setting: a cumulative sum analysis of operative length.

BACKGROUND: Cumulative sum (CUSUM) analysis is a valuable tool for quantifying the learning curve of surgical teams by detecting significant changes in operative length. However, there is limited research evaluating the learning curve of laparoscopic techniques in low-resource settings. The objective of this study is to evaluate the learning curve for laparoscopic appendectomy within a single surgical team in Senegal. METHODS: This was a single-center prospective study conducted from May 1, 2018, to August 31, 2023 of patients who underwent laparoscopic appendectomy at a tertiary care institution in West Africa. The AAST classification was used to describe the severity of appendicitis. Parameters studied included age, sex, operative length, conversion rate, and postoperative outcomes. To quantify the learning curve, CUSUM analysis of operative length was performed. RESULTS: A total of 81 patients were included. The mean age was 26.7 years (range 11-70 years) with a sex ratio of 1.9. Pre-operative severity according to AAST was Grade I in 75.4% (n = 61), Grade III in 7.4% (n = 6), Grade IV in 6.1% (n = 5), and Grade V in 11.1% (n = 9). Conversion occurred in 5 cases (6.1%). The average operative length was 76.8 min (range 30-180 min) and the average length of hospitalization was 2.7 days (range 1-13 days). Morbidity was observed in 3.7% (n = 3) and there were no deaths. The CUSUM analysis showed that a steady operative length was achieved after 28 procedures, with decreasing operative lengths thereafter. CONCLUSION: Surgeons in our setting overcame the learning curve for laparoscopic appendectomy after performing 28 procedures. Moreover, laparoscopic appendectomy is safe and feasible throughout the learning curve. CUSUM analysis should be applied to other laparoscopic procedures and individualized by surgical teams to improve surgical performance and patient outcomes in low-resource settings.

Plasmid-mediated horizontal gene mobilisation: Insights from two lactococcal conjugative plasmids.

The distinct conjugation machineries encoded by plasmids pNP40 and pUC11B represent the most prevalent plasmid transfer systems among lactococcal strains. In the current study, we identified genetic determinants that underpin pNP40- and pUC11B-mediated, high-frequency mobilisation of other, non-conjugative plasmids. The mobilisation frequencies of the smaller, non-conjugative plasmids and the minimal sequences required for their mobilisation were determined, owing to the determination of the oriT sequences of both pNP40 and pUC11B, which allowed the identification of similar sequences in some of the non-conjugative plasmids that were shown to promote their mobilisation. Furthermore, the auxiliary gene mobC, two distinct functional homologues of which are present in several plasmids harboured by the pNP40- and pUC11B-carrying host strains, was observed to confer a high-frequency mobilisation phenotype. These findings provide mechanistic insights into how lactococcal conjugative plasmids achieve conjugation and promote mobilisation of non-conjugative plasmids. Ultimately, these insights would be harnessed to optimise conjugation and mobilisation strategies for the rapid and predictable development of robust and technologically improved strains.

Discovering genetic determinants for cell-to-cell adhesion in two prevalent conjugative lactococcal plasmids.

Plasmids pNP40 and pUC11B encode two prevalent yet divergent conjugation systems, which have been characterized in detail recently. Here, we report the elucidation of the putative adhesins of the pNP40 and pUC11B conjugation systems, encoded by traAd and trsAd, respectively. Despite their significant sequence divergence, TraAd and TrsAd represent the most conserved component between the pNP40- and the pUC11B-encoded conjugation systems and share similar peptidoglycan-hydrolase domains. Protein structure prediction using AlphaFold2 highlighted the structural similarities between their predicted domains, as well as the potential homo-dimeric state of both proteins. Expression of the putative surface adhesins resulted in a cell clumping phenotype not only among cells expressing these surface adhesins but also between adhesin-expressing and non-producing cells. Furthermore, mutant derivatives of plasmids pNP40 or pUC11B carrying a mutation in traAd or trsAd, respectively, were shown to act as efficient donors provided the corresponding recipient expresses either traAd or trsAd, thus demonstrating in trans reciprocal complementarity of these proteins in conjugation systems.

Enteral Access Outcomes in Patients Hospitalized With Cardiac Disease: A Retrospective Cohort Study.

INTRODUCTION: Patients admitted with principal cardiac diagnosis (PCD) can encounter difficult inpatient stays that are often marked by malnutrition. In this setting, enteral feeding may improve nutritional status. This study examined the association of PCD with perioperative outcomes after elective enteral access procedures. METHODS: Adult patients who underwent enteral access procedures between 2018 and 2020 at a tertiary care institution were reviewed retrospectively. Differences in baseline characteristics between patients with and without PCD were adjusted using entropy balancing. Multivariable logistic and linear regressions were subsequently developed to evaluate the association between PCD and nutritional outcomes, perioperative morbidity and mortality, length of stay, and nonelective readmission after enteral access. RESULTS: 912 patients with enteral access met inclusion criteria, of whom 84 (9.2%) had a diagnosis code indicating PCD. Compared to non-PCD, patients with PCD more commonly received percutaneous endoscopic gastrostomy by general surgery and had a higher burden of comorbidities as measured by the Charlson comorbidity index. Multivariable risk adjustment generated a strongly balanced distribution of baseline covariates between patient groups (standardized differences ranged from -2.45 × 10-8 to 3.18 × 108). After adjustment, despite no significant association with in-hospital mortality, percentage change prealbumin, length of stay, or readmission, PCD was associated with an approximately 2.25-day reduction in time to meet goal feeds (95% CI -3.76 to -0.74, P = 0.004) as well as decreased odds of reoperation (adjusted odds ratio 0.28, 95% CI 0.09-0.86, P = 0.026) and acute kidney injury (adjusted odds ratio 0.24, 95% CI 0.06-0.91, P = 0.035). CONCLUSIONS: Despite having more comorbidities than non-PCD, adult enteral access patients with PCD experienced favorable nutritional and perioperative outcomes.

Immunohistochemical staining with CD117 and PGP9.5 of excised vestibular tissue from patients with neuroproliferative vestibulodynia.

BACKGROUND: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8 CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining. AIM: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes. METHODS: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o'clock region (P < .001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P = .011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity. CLINICAL IMPLICATIONS: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging. STRENGTHS AND LIMITATIONS: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues. CONCLUSIONS: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge.

Sleeve Gastrectomy Reduces the Need for Liver Transplantation in Patients with Obesity and Non-Alcoholic Steatohepatitis: a Predictive Model.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is one of the leading indications for liver transplantation (LT) in the United States. As with the current obesity epidemic, the incidence of NASH continues to rise. However, the impact of broad utilization of bariatric surgery (BS) for patients with NASH is unknown, particularly in regard to mitigating the need for LT. METHODS: Markov decision analysis was performed to simulate the lives of 20,000 patients with obesity and concomitant NASH who were deemed ineligible to be waitlisted for LT unless they achieved a body mass index (BMI) < 35 kg/m2. Life expectancy following medical weight management (MWM) and sleeve gastrectomy (SG) were estimated. Base case patients were defined as having NASH without fibrosis and a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. RESULTS: Simulated base case analysis patients who underwent SG gained 14.3 years of life compared to patients who underwent MWM. One year after weight loss intervention, 9% of simulated MWM patients required LT compared to only 5% of SG patients. Survival benefit for SG was observed above a BMI of 32.2 kg/m2. CONCLUSION: In this predictive model of 20,000 patients with obesity and concomitant NASH, surgical weight loss is associated with a reduction in the progression of NASH, thereby reducing the need for LT. A reduced BMI threshold of 32 kg/m2 for BS may offer survival benefit for patients with obesity and NASH.

Transcriptional control of two distinct lactococcal plasmid-encoded conjugation systems.

Lactococcal conjugative plasmids are poorly characterized compared to those harbored by numerous other Gram-positive bacteria, despite their significance in dairy fermentations and starter culture development. Furthermore, the transcriptional landscape of these lactococcal conjugation systems and their regulation have not been studied in any detail. Lactococcal plasmids pNP40 and pUC11B possess two genetically distinct and prevalent conjugation systems. Here, we describe the detailed transcriptional analysis of the pNP40 and pUC11B conjugation-associated gene clusters, revealing three and five promoters, respectively, for which the corresponding transcriptional start sites were identified. Regulation of several of these promoters, and therefore conjugation, is shown to involve the individual or concerted activities of the corresponding relaxase and transcriptional repressor(s) encoded by each conjugative plasmid. This work highlights how the conjugative potential of these systems may be unlocked, with significant implications for the starter culture and food fermentation industry.

A Systematic Review of Immersive Virtual Reality for Nontechnical Skills Training in Surgery.

OBJECTIVE: Immersive virtual reality (IVR) can be utilized to provide low cost and easily accessible simulation on all aspects of surgical education. In addition to technical skills training in surgery, IVR simulation has been utilized for nontechnical skills training in domains such as clinical decision-making and pre-operative planning. This systematic review examines the current literature on the effectiveness of IVR for nontechnical skill acquisition in surgical education. DESIGN: A literature search was performed using MEDLINE, EMBASE, and Web of Science for primary studies published between January 1, 1995 and February 9, 2022. Four reviewers screened titles, abstracts, full texts, extracted data, and analyzed included studies to answer 5 key questions: How is IVR being utilized in nontechnical skills surgical education? What is the methodological quality of studies? What technologies are being utilized? What metrics are reported? What are the findings of these studies? RESULTS: The literature search yielded 2340 citations, with 12 articles included for qualitative synthesis. Of included articles, 33% focused on clinical decision-making and 67% on anatomy/pre-operative planning. Motion sickness was a recorded metric in 25% of studies, with an aggregate incidence of 13% (11/87). An application score was reported in 33% and time to completion in 16.7%. A commercially developed application was utilized in 25%, while 75% employed a noncommercial application. The Oculus Rift was used in 41.7% of studies, HTC Vive in 25%, Samsung Gear in 16.7% of studies, Google Daydream in 8%, and 1 study did not report. The mean Medical Education Research Quality Instrument (MERSQI) score was 10.3 ± 2.3 (out of 18). In all studies researching clinical decision-making, participants preferred IVR to conventional teaching methods and in a nonrandomized control study it was found to be more effective. Averaged across all studies, mean scores were 4.33 for enjoyment, 4.16 for utility, 4.11 for usability, and 3.73 for immersion on a 5-point Likert scale. CONCLUSIONS: The IVR nontechnical skills applications for surgical education are designed for clinical decision-making or anatomy/pre-operative planning. These applications are primarily noncommercially produced and rely upon a diverse array of HMDs for content delivery, suggesting that development is primarily coming from within academia and still without clarity on optimal utilization of the technology. Excitingly, users find these applications to be immersive, enjoyable, usable, and of utility in learning. Although a few studies suggest that IVR is additive or superior to conventional teaching or imaging methods, the data is mixed and derived from studies with weak design. Motion sickness with IVR remains a complication of IVR use needing further study to determine the cause and means of mitigation.

Ventricular Remodeling Following Metabolic and Bariatric Surgery Decreases Need for Heart Transplantation: A Predictive Model.

PURPOSE: For patients with obesity and congestive heart failure (CHF) who require heart transplantation (HT), aggressive weight loss has been associated with ventricular remodeling, or subclinical alterations in left and right ventricular structure that affect systolic function. Many have suggested offering metabolic and bariatric surgery (MBS) for these patients. As such, we evaluated the role of MBS in HT for patients with obesity and CHF using predictive modelling techniques. MATERIALS AND METHODS: Markov decision analysis was performed to simulate the life expectancy of 30,000 patients with concomitant obesity, CHF, and 30% ejection fraction (EF) who were deemed ineligible to be waitlisted for HT unless they achieved a BMI < 35 kg/m2. Life expectancy following diet and exercise (DE), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) was estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. RESULTS: RYGB patients had lower rates of HT and received HT quicker when needed. Base case patients who underwent RYGB gained 2.2 additional mean years survival compared with patients who underwent SG and 10.3 additional mean years survival compared with DE. SG patients gained 6.2 mean years of life compared with DE. CONCLUSION: In this simulation of 30,000 patients with obesity, CHF, and reduced EF, MBS was associated with improved survival by not only decreasing the need for transplantation due to improvements in EF, but also increasing access to HT when needed due to lower average BMI.

Princeton IV consensus guidelines: PDE5 inhibitors and cardiac health.

BACKGROUND: In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13 years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions, but also a potential cardioprotective effect of these drugs. AIM: In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the Huntington Medical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach to treatment of ED in men with known cardiovascular disease. METHOD: A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus. OUTCOMES: Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors. RESULTS: An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug-drug interactions; optimizing use of a PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non-PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non-PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed. CLINICAL IMPLICATIONS: Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease. STRENGTHS AND LIMITATIONS: Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting. CONCLUSION: The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors.

Ethical Guidance for Physicians and Health Care Institutions on Grateful Patient Fundraising: A Position Paper From the American College of Physicians.

Physician solicitation of charitable contributions from patients-also known among other things as grateful patient fundraising-raises significant ethical concerns. These include pressure on patients to donate and the effects of this on the patient-physician relationship, potential expectations of donor patients for treatment that is not indicated or preferential care, justice and fairness issues, disclosure and use of confidential patient information for nontreatment purposes, and conflicts of interest. The patient-physician relationship and knowledge of the patient's medical history, clinical status, personal information, and financial circumstances are some of the reasons development and administrative officials might see physicians as strong potential fundraisers. But those are among the reasons grateful patient fundraising is ethically problematic. This American College of Physicians position paper explores these issues and offers guidance.

Factors associated with conversion in laparoscopic surgery in a low-resource setting: a single-center prospective study.

INTRODUCTION: Laparoscopy has a clear patient benefit related to postoperative morbidity but may not be as commonly performed in low-and middle-income countries. The decision to convert to laparotomy can be complex and involve factors related to the surgeon, patient, and procedure. The objective of this work is to analyze the factors associated with conversion in laparoscopic surgery in a low-resource setting. METHODS: This is a single-center prospective study of patients who underwent laparoscopic surgery between May 1, 2018 and October 31, 2021. The parameters studied were age, sex, body mass index (BMI), intraoperative complication (e.g., accidental enterotomy, hemorrhage), equipment malfunction (e.g., technical failure of the equipment, break in CO2 supply line), operating time, and conversion rate. RESULTS: A total of 123 laparoscopic surgeries were performed. The average age of patients was 31.2 years (range 11-75). The procedures performed included appendix procedures (48%), followed by gynecological (18.7%), gallbladder (14.6%), digestive (10.56%), and abdominal procedures (4%). The average length of hospitalization was 3 days (range 1-16). Conversion to laparotomy was reported in 8.9% (n = 11) cases. Equipment malfunction was encountered in 9.8% (n = 12) cases. Surgical complications were noted in 11 cases (8.9%). Risk factors for conversion were shown to be BMI > 25 kg/m2 (OR 4.6; p = 0.034), intraoperative complications (OR 12.6; p = 0.028), and equipment malfunction (OR 9.4; p = 0.002). CONCLUSION: A better understanding of the underlying factors associated with high conversion rates, such as overweight/obesity, intraoperative complications, and equipment failure, is the first step toward surgical planning to reduce postoperative morbidity in low-resource settings.

Vestibular tissue changes following administration of intravaginal prasterone: a vulvoscopic open-label pilot study in menopausal women with dyspareunia.

Background: Prasterone, an intravaginal dyspareunia treatment in menopausal women, improves vaginal health through intracellular conversion of dehydroepiandrosterone into androgens and estrogens. Phase 3 trials for prasterone showed significant improvement in vaginal tissue health and reduction of pain. Aim: To assess vestibular changes with daily use of intravaginal prasterone in menopausal women with moderate to severe dyspareunia. Methods: This open-label prospective pilot study was conducted over 20 weeks. It included 11 menopausal women (median age, 56 years) who were treated daily with intravaginal inserts of 6.5-mg prasterone and assessed monthly. During vulvoscopy, vestibular pain was assessed by cotton-tipped swab testing, and vestibular and vaginal health was independently assessed with the Visual Scale (VS). In addition, vulvoscopic photographs were obtained and assessed via the Vulvoscopic Genital Tissue Appearance (VGTA) scale to evaluate overall genital tissue health. Mean changes from baseline for genital tissue health and pain assessments were analyzed by repeated measures 1-way analysis of variance, followed by a Dunnett post hoc test. Sexual event diaries were completed and adverse events recorded. Outcomes: Outcomes included indices of genital tissue health: pain assessment by cotton-tipped swab testing, VS of the vestibule and vagina, VGTA, and sexual event diary. Results: Aggregate scores from the cotton-tipped swab test progressively improved, reaching statistical significance at week 16, which was maintained through week 20 (-7.27, P = .019). VS scores significantly improved from baseline by week 4 and were maintained through week 20 for the vestibule (-3.00, P = .004) and vagina (-4.00, P = .002). An overall 1607 vulvoscopic photographs were examined; all showed reduction in vestibular erythema and pallor at the end of the study. The mean change from baseline at week 20 for the VGTA score was -7.9 (P = .0016). Intercourse associated with pain was reduced from 81.3% of initiated events during the first month of the study to 8.3% during the last month. Sexual activities that were discontinued due to discomfort were reduced from 45.8% to 6.3%. No prasterone-related serious adverse events were reported. Clinical Implications: Prasterone, a safe and effective intravaginal hormone treatment, significantly improves vestibular health parameters. Strengths and Limitations: Strengths are the prospective study design and the use of multiple outcome measures to assess vestibular tissue health and pain associated with sexual activity. Limitations are the small study cohort and use of nonvalidated outcome measures. Conclusion: Our findings suggest that intravaginal prasterone exerts biologic activity on the androgenic endodermal vestibule, as the medication passes from vagina to vestibule, resulting in amelioration of pain associated with sexual activity.

Evolution of laparoscopic surgery in a sub-Saharan African country: a 30-year literature review in Senegal.

INTRODUCTION: The advent of laparoscopy has significantly reduced the morbidity associated with the majority of abdominal surgeries. In Senegal, the first studies evaluating this technique were published in the 1980s. The objective of this systematic review is to assess the evolution of laparoscopy research in Senegal. METHODS: A search of PubMed and Google Scholar was carried out without limit of publication date. The keywords used were "senegal" AND "laparoscop*". Duplicates were removed, and remaining articles were assessed for selection criteria. We included all articles about laparoscopy published in Senegal. The parameters studied in each included article were the place and year of study, average age, sex ratio, assessed indications and results. RESULTS: 41 Studies published between 1984 and 2021 met selection criteria. The average age of patients was 33 years (range 4.7-63). The sex ratio was 0.33. The main indications for laparoscopy according to the studies were: benign gastrointestinal disorders in 11 studies (26.8%), abdominal emergencies in 9 studies (22%), gallbladder surgery in 5 studies (12.2%), benign gynecological pathology in 6 studies (14.6%), malignant gynecological pathology in 2 studies (4.9%), diagnostic laparoscopy in 2 studies (4.9%), groin hernia repair in 2 studies (4.9%) and testicular pathology in 1 study (2.4%). Overall mortality was estimated at 0.9% (95% CI 0.6-1.3) and overall morbidity for all complications was estimated at 5% (95% CI 3.4-6.9). CONCLUSIONS: This systematic review showed a predominance of the laparoscopy publications from the capital in Dakar with favorable outcomes. This technique should be popularized in the different regions of the country and its indications expanded.

Evaluation of the educational quality of publicly available online videos on laparoscopic jejunostomy by utilizing the LAP-VEGaS guidelines.

BACKGROUND: Despite its common nature, there is no data on the educational quality of publicly available laparoscopic jejunostomy training videos. The LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool, released in 2020, has been developed to ensure that teaching videos are of appropriate quality. This study applies the LAP-VEGaS tool to currently available laparoscopic jejunostomy videos. METHODS: A retrospective review of YouTube® videos was conducted for "laparoscopic jejunostomy." Included videos were rated by three independent investigators using LAP-VEGaS video assessment tool (0-18). Wilcoxon rank-sum test was used to evaluate differences in LAP-VEGaS scores between video categories and date of publication relative to 2020. Spearman's correlation test was performed to measure association between scores and length, number of views and likes. RESULTS: 27 unique videos met selection criteria. Academic and physician video walkthroughs did not demonstrate a significant difference in median scores (9.33 IQR 6.33, 14.33 vs. 7.67 IQR 4, 12.67, p = 0.3951). Videos published after 2020 demonstrated higher median scores than those published before 2020 (13 IQR 7.5, 14.67 vs. 5 IQR 3, 9.67, p = 0.0081). A majority of videos failed to provide patient position (52%), intraoperative findings (56%), operative time (63%), graphic aids (74%), and audio/written commentary (52%). A positive association was demonstrated between scores and number of likes (rs = 0.59, p = 0.0011) and video length (rs = 0.39, p = 0.0421), but not number of views (rs = 0.17, p = 0.3991). CONCLUSION: The majority of available YouTube® videos on laparoscopic jejunostomy fail to meet the basic educational needs of surgical trainees, and there is no difference between those produced by academic centers or independent physicians. However, there has been improvement in video quality following the release of the scoring tool. Standardization of laparoscopic jejunostomy training videos with the LAP-VEGaS score can ensure that videos are of appropriate educational value with logical structure.