Maternal Cardiovascular Health Post-Dobbs.

Maternal Cardiovascular Health Post-DobbsPregnancy is associated with increasing morbidity and mortality in the United States. In the post-Dobbs era, many pregnant patients at highest risk no longer have access to abortion, which has been a crucial component of standard medical care.

Should Current Laws Be Revised to Address Occupational Hazards Caused by Hand-Tool Size Mismatch Among Surgeons?

This Viewpoint discusses the challenges faced by surgeons with a smaller hand size­and women in particular­when using surgical tools designed for larger hands and explores potential legal remedies to address these challenges.

Whose Responsibility Is It to Define Exceptions in Abortion Bans?

This Viewpoint evaluates Texas' proposals to define the scope of the life exception for the state's abortion ban and argues that these approaches do not allow physicians to follow the national standards of care, avoid criminal liability, or have sufficient notice of what the law permits.

Harvey and Gurvir's Law: The Need for Accurate Information Balanced Against Avoiding Unnecessary Restrictions on Autonomous Decision Making.

Decision making during reproduction is complex for a variety of medical and social reasons. Anyone who has had a conversation with a family member about the "best time" to have a baby can attest to this - there is no "best time" or "best way." Multiple pressures from any number of sources combine in a minefield of hazards made ever more complicated by restrictive laws in the US. Add to this a screening result of potential chromosomal aneuploidy and decision making becomes ever more complex. Societal stigma and lack of adequate and accurate information during counseling certainly plays a role in the high number of terminations in the setting of diagnosed chromosomal aneuploidy, yet other factors also push families in this direction including medical considerations and the abysmal lack of social support programs.

Abortion restrictions and medical residency applications.

Residency selection is a challenging process for medical students, one further complicated in the USA by the recent Dobbs v Jackson Women's Health Organization (Dobbs) decision over-ruling the federal right to abortion. We surveyed medical students to examine how Dobbs is influencing the ideological, personal and professional factors they must reconcile when choosing where and how to complete residency.Between 6 August and 22 October 2022, third-year and fourth-year US medical students applying to US residency programmes were surveyed through social media and direct outreach to medical schools. Analysis of quantitative and qualitative data from 494 responses was performed to assess downstream effects of Dobbs on residency applicants' family, health and career choices.Most respondents said changes in abortion access would likely or very likely influence their decision regarding location of considered residency programme (76.9%), where to start a family (72.2%) and contraceptive planning for them or their partner (57.9%). Cis-gender females were more influenced by Dobbs regarding where (5 (4, 5) p<0.001) and when (3 (3, 5) p<0.001) to start a family. In qualitative responses, medical trainees highlighted the importance of abortion access for their patients, themselves and their loved ones.Medical trainees are incorporating state abortion access into their residency programme choices. Future physicians care about both the quality of care they will be able to provide and their own health. For personal and professional reasons, reproductive healthcare access is now a key factor in residency match decisions.

Expanding roles of BCL-2 proteins in apoptosis execution and beyond.

The proteins of the BCL-2 family are known as key regulators of apoptosis, with interactions between family members determining permeabilisation of the mitochondrial outer membrane (MOM) and subsequent cell death. However, the exact mechanism through which they form the apoptotic pore responsible for MOM permeabilisation (MOMP), the structure and specific components of this pore, and what roles BCL-2 proteins play outside of directly regulating MOMP are incompletely understood. Owing to the link between apoptosis dysregulation and disease, the BCL-2 proteins are important targets for drug development. With the development and clinical use of drugs targeting BCL-2 proteins showing success in multiple haematological malignancies, enhancing the efficacy of these drugs, or indeed developing novel drugs targeting BCL-2 proteins is of great interest to treat cancer patients who have developed resistance or who suffer other disease types. Here, we review our current understanding of the molecular mechanism of MOMP, with a particular focus on recently discovered roles of BCL-2 proteins in apoptosis and beyond, and discuss what implications these functions might have in both healthy tissues and disease.

Insemination "Fraud": Potentially Criminal Actions in Reproductive Medicine.

Case law and statutory provisions ensure marital rules of paternity apply when artificial insemination is associated with the pregnancy. Virtually all jurisdictions in the United States provide for gamete donors to remain anonymous. Much of this has been challenged with access to donor information via 23 and me. A breach of trust and a number of lawsuits involving physician provider(s) have resulted. We provide case law examples related to artificial insemination and the identification of the sperm donor. Proposed future legislation to protect patients and offspring from harm in relation to the process of donor sperm inseminations is provided.

Very Low Rates of Ureteral Injury in Laparoscopic Hysterectomy Performed by Fellowship-trained Minimally Invasive Gynecologic Surgeons.

STUDY OBJECTIVE: The objective of this case series is to evaluate the rates of ureteral injury at the time of laparoscopic hysterectomy among high-volume fellowship-trained surgeons. DESIGN: A retrospective chart review was performed, evaluating laparoscopic hysterectomy cases between 2009 and 2019 performed exclusively by fellowship-trained surgeons. SETTING: Division of Minimally Invasive Gynecologic Surgery (MIGS) at the Brigham and Women's Hospital and Brigham and Women's Faulkner Hospital, a Harvard Medical School teaching hospital in Boston. PATIENTS: All patients undergoing laparoscopic hysterectomy by one of 5 surgeons with fellowship training in MIGS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 5160 cases were handled by MIGS surgeons between 2009 and 2019 at our institution. Of these cases, 2345 were laparoscopic hysterectomy cases with available intraoperative and postoperative documentation. Most patients had undergone previous surgeries, and the most common indications for hysterectomy included uterine myomas, pelvic pain/endometriosis, and abnormal uterine bleeding. At the time of hysterectomy, 1 ureteral injury (0.04%) was noted. No additional delayed ureteral injuries were observed. Most patients were discharged home the same day (64.9%) and did not have any postoperative complications (63.9%) as designated by the Clavien-Dindo classification. CONCLUSION: Ureteral injury, although rare, is more prevalent in gynecologic surgery than in other surgical disciplines that have some focus on the pelvis. No study to date has evaluated the effect of surgical training and volume on rates of ureteral injuries. This study retrospectively examined ureteral injury rates for one group of high-volume fellowship-trained surgeons and found their rates to be lower than the national average. Proposals are presented for optimizing training and delivery of gynecologic surgical care to minimize complications.

Apoptotic priming is defined by the dynamic exchange of Bcl-2 proteins between mitochondria and cytosol.

Apoptosis is regulated by interactions between the BH3-only and multi-domain Bcl-2 family proteins. These interactions are integrated on the outer mitochondrial membrane (OMM) where they set the threshold for apoptosis, known as mitochondrial priming. However, how mitochondrial priming is controlled at the level of single cells remains unclear. Retrotranslocation of Bcl-XL has been proposed as one mechanism, removing pro-apoptotic Bcl-2 proteins from the OMM, thus reducing priming. Contrary to this view, we now show that Bcl-XL retrotranslocation is inhibited by binding to its BH3-only partners, resulting in accumulation of these protein complexes on mitochondria. We find that Bcl-XL retrotranslocation dynamics are tightly coupled to mitochondrial priming. Quantifying these dynamics indicates the heterogeneity in priming between cells within a population and predicts how they subsequently respond to a pro-apoptotic signal.

BCL-2-family protein tBID can act as a BAX-like effector of apoptosis.

During apoptosis, the BCL-2-family protein tBID promotes mitochondrial permeabilization by activating BAX and BAK and by blocking anti-apoptotic BCL-2 members. Here, we report that tBID can also mediate mitochondrial permeabilization by itself, resulting in release of cytochrome c and mitochondrial DNA, caspase activation and apoptosis even in absence of BAX and BAK. This previously unrecognized activity of tBID depends on helix 6, homologous to the pore-forming regions of BAX and BAK, and can be blocked by pro-survival BCL-2 proteins. Importantly, tBID-mediated mitochondrial permeabilization independent of BAX and BAK is physiologically relevant for SMAC release in the immune response against Shigella infection. Furthermore, it can be exploited to kill leukaemia cells with acquired venetoclax resistance due to lack of active BAX and BAK. Our findings define tBID as an effector of mitochondrial permeabilization in apoptosis and provide a new paradigm for BCL-2 proteins, with implications for anti-bacterial immunity and cancer therapy.

Analysis of COVID-19 Response and Impact on Gynecologic Surgery at a Large Academic Hospital System.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic dramatically impacted gynecologic surgery. In March 2020, the American College of Surgeons recommended delay of all nonessential invasive procedures. This study characterizes the number and types of procedures performed during the peak pandemic. METHODS: A retrospective cohort study was performed. All patients undergoing gynecological surgery at a large academic hospital system from March 16, 2019 to July 31, 2019 and from March 16, 2020 to July 31, 2020 were evaluated. Data was stratified by three time periods corresponding to state and hospital policy changes. During period 1, no nonessential procedures were advised. During period 2, urgent procedures resumed. During period 3, full surgical reopening was achieved. RESULTS: In 2019, 1,545 gynecologic cases were performed compared with 942 cases in 2020 (39.0% decrease). There was a 73.6% decrease in cases over period 1, a 20.1% decrease over period 2, and a 2.9% increase over period 3. Cases performed by gynecologic oncologists in 2020 accounted for 58.1% of all gynecologic cases over period 1, 29.4% of cases over period 2, and 33.3% of cases over period 3. In 2020, hysterectomy was the most commonly performed procedure, while surgery for endometriosis and uterine fibroids had the greatest decrease in volume. Among emergency procedures, more surgery for ectopic pregnancy was performed in 2020 compared with 2019. CONCLUSION: Many patients had significant delays in receiving gynecologic surgical care during the peak pandemic period. Further studies are indicated to determine the impact of delayed care on patients' quality of life and disease process.

Apoptosis regulation at the mitochondria membrane level.

Mitochondrial outer membrane permeabilization (MOMP) is a key checkpoint in apoptosis that activates the caspase cascade and irreversibly causes the majority of cells to die. The proteins of the Bcl-2 family are master regulators of apoptosis that form a complex interaction network within the mitochondrial membrane that determines the induction of MOMP. This culminates in the activation of the effector members Bax and Bak, which permeabilize the mitochondrial outer membrane to mediate MOMP. Although the key role of Bax and Bak has been established, many questions remain unresolved regarding molecular mechanisms that control the apoptotic pore. In this review, we discuss the recent progress in our understanding of the regulation of Bax/Bak activity within the mitochondrial membrane.

Lung inflammation and simulated airway resistance in infants with cystic fibrosis.

Cystic fibrosis (CF) is characterized by small airway disease; but central airways may also be affected. We hypothesized that airway resistance estimated from computational fluid dynamic (CFD) methodology in infants with CF was higher than controls and that early airway inflammation in infants with CF is associated with airway resistance. Central airway models with a median of 51 bronchial outlets per model (interquartile range 46,56) were created from chest computed tomography scans of 18 infants with CF and 7 controls. Steady state airflow into the trachea was simulated to estimate central airway resistance in each model. Airway resistance was increased in the full airway models of infants with CF versus controls and in models trimmed to 33 bronchi. Airway resistance was associated with markers of inflammation in bronchoalveolar lavage fluid obtained approximately 8 months earlier but not with markers obtained at the same time. In conclusion, airway resistance estimated by CFD modeling is increased in infants with CF compared to controls and may be related to early airway inflammation.

Ending Restraint of Incarcerated Individuals Giving Birth.

Advocates have long suggested making shackling incarcerated people during childbirth illegal. Yet exceptions would likely still allow prison personnel to implement restraint and leave clinicians no course for freeing a patient. This article argues that clinicians' assessments of laboring individuals' clinical needs must be prioritized, ethically and legally. This article also explains that, without strong policies in place, some clinicians will not feel empowered to demand that a patient be freed during labor. Beyond prohibiting restraint of laboring individuals, health care organizations must support clinicians seeking to execute their ethical duties to care well and justly for patients. Toward this end, this article proposes a model policy.

The clinical features that contribute to poor bone health in young Australians living with cystic fibrosis: A recommendation for BMD screening.

BACKGROUND: For Australians living with cystic fibrosis (CF), increased longevity means greater consideration needs to be given to long-term endocrine sequelae such as CF-related bone disease. Deficits in bone mass accrual are most likely to occur during childhood and adolescence. Current guidelines in Australia suggest repeat dual-energy X-ray absorptiometry (DXA) scans every 2 years. This study aims to stratify clinical factors that determine future bone health in the Australian CF population and use this to guide a more streamlined approach to bone health screening. METHODS: This study was a retrospective audit of all patients diagnosed with CF who were treated at the Royal Children's Hospital Melbourne, Australia from 2000 to 2016 (n = 453). Two hundred and two patients had a DXA scan in the study period (191 with height-adjusted data) and 111 patients had more than one scan (108 with height-adjusted data). An investigation into the associations between bone mineral density (BMD) Z score and potential risk factors was conducted using DXA and historical data. RESULTS: The main predictor of future BMD was the previous BMD Z score (p < .001). Other factors found to be determinants of BMD included nutritional status, lung function (FEV1 ), age, history of previous fracture, oral corticosteroid use, and the number of hospital admissions. However, after adjusting for previous BMD, evidence of an association remained only with nutritional status, FEV1 , and number of hospital admissions. CONCLUSION: Second yearly scans may be unnecessary in children with an adequate DXA score on the initial scan who remain clinically stable. However, clinical deterioration in those whose BMD was previously normal, may require closer monitoring of bone health. We propose a guideline for the frequency of DXA monitoring in relation to clinical risk factors.

Double Discrimination, the Pay Gap in Gynecologic Surgery, and Its Association With Quality of Care.

In this commentary, we describe historical and other influences that drive "double discrimination" in gynecologic surgery-lower pay in the area of surgery that boasts the largest proportion of female surgeons and is focused on female patients and explore how it results in potentially lower quality care. Insurers reimburse procedures for women at a lower rate than similar procedures for men, although there is no medically justifiable reason for this disparity. The wage gap created by lower reimbursement rates disproportionately affects female surgeons, who are disproportionately represented among gynecologic surgeons. This contributes to a large wage gap in surgery for women. Finally, poor reimbursement for gynecologic surgery pushes many obstetrics and gynecology surgeons to preferentially perform obstetric services, resulting in a high prevalence of low-volume gynecologic surgeons, a metric that is closely tied to higher complication rates. Creating equity in reimbursement for gynecologic surgery is one important and ethically required step forward to gender equity in medicine for patients and surgeons.