Anesthesia for gender-affirming surgery: a practical review.

PURPOSE OF REVIEW: Gender-affirming surgery (GAS) is an effective, well studied, and often necessary component of gender-affirming care and mitigation of gender dysphoria for transgender and gender-diverse (TGD) individuals. GAS is categorized as chest surgeries, genitourinary surgeries, facial feminization/masculinization, and vocal phonosurgery. Despite increased incidence of GAS during recent years, there is a gap in knowledge and training on perioperative care for TGD patients. RECENT FINDINGS: Our review discusses the relevant anesthetic considerations for the most common GAS, which often involve highly specialized surgical techniques that have unique implications for the anesthesia professional. SUMMARY: Anesthesiology professionals must attend to the surgical and anesthetic nuances of various GAS procedures. However, as many considerations are based on common practice, research is warranted on anesthetic implications and outcomes of GAS.

Provider cultural competence and humility in healthcare interactions with transgender and nonbinary young adults.

PURPOSE: Transgender and nonbinary (TGNB) patients experience many barriers when seeking quality healthcare services, including ineffective communication and negative relationships with their providers as well as a lack of provider competence (including knowledge, training, and experience) and humility (engagement in the process of self-reflection and self-critique) in treating TGNB individuals. The purpose of this qualitative study was to identify factors associated with cultural competence and humility that facilitate and impede effective relationships between TGNB young adults and their healthcare providers. METHODS: Data came from individual interviews with 60 young adults aged 18 to 24 from Florida who self-identified as transgender or nonbinary. We analyzed the data using inductive thematic approaches, and a feminist perspective, to identify themes associated with patient-provider relationships. CONCLUSIONS: We identified 4 themes related to patient-provider relationships: (1) Participants indicated effective patient-provider communication and relationships are facilitated by providers requesting and utilizing TGNB patients' correct names and personal pronouns. (2) Participant narratives conveyed their preferences that providers "follow their lead" in terms of how they described their own anatomy, reinforcing the utility of cultural humility as an approach for interactions with TGNB patients (3) Participants discussed the detrimental effects of TGNB patients having to educate their own providers about their identities and needs, suggesting clinicians' competence regarding gender diversity is paramount to fostering and maintaining patient comfort. (4) Finally, participants' responses indicated concerns regarding the confidentiality and privacy of the information they provided to their providers, suggesting a lack of trust detrimental to the process of building rapport between patients and their providers. CLINICAL RELEVANCE: Our findings indicate balancing the use of cultural humility and cultural competence during clinical encounters with TGNB young adults can enhance patients' experiences seeking healthcare. Nursing education is often devoid of focus on caring for transgender and nonbinary persons. Additional provider training and education on approaching clinical encounters with TGNB patients with cultural humility and competence should improve patient-provider communication and relationships, leading to a higher quality of patient care.

A Case Report of Tension Hydrothorax Incited by Bowel Perforation.

We report the case of a 34-year-old man who developed cardiac arrest due to tension hydrothorax from colonic perforation. Tension hydrothorax, an entity characterized by pleural effusion leading to mediastinal compression, has not been reported in association with intraabdominal inflammation. Our patient developed respiratory insufficiency after repair of colonic perforation, followed by respiratory failure and cardiac arrest. Transthoracic echocardiography provided rapid diagnosis during decompensation and prompted a lifesaving thoracostomy. Clinicians should consider tension hydrothorax as a rare cause of hemodynamic collapse, even in the absence of liver failure, and use bedside tools like transthoracic echocardiography to facilitate diagnosis and intervention.

Perioperative Care of Transgender and Gender-Diverse Patients: A Biopsychosocial Approach.

Transgender and gender-diverse (TGD) people endure numerous physical and mental health disparities secondary to lifelong stigma and marginalization, which are often perpetuated in medical spaces. Despite such barriers, TGD people are seeking gender-affirming care (GAC) with increased frequency. GAC facilitates the transition from the sex assigned at birth to the affirmed gender identity and is comprised of hormone therapy (HT) and gender-affirming surgery (GAS). The anesthesia professional is uniquely poised to serve as an integral support for TGD patients within the perioperative space. To provide affirmative perioperative care to TGD patients, anesthesia professionals should understand and attend to the biological, psychological, and social dimensions of health that are relevant to this population. This review outlines the biological factors that impact the perioperative care of TGD patients, such as the management of estrogen and testosterone HT, safe use of sugammadex, interpretation of laboratory values in the context of HT, pregnancy testing, drug dosing, breast binding, altered airway and urethral anatomy after prior GAS, pain management, and other GAS considerations. Psychosocial factors are reviewed, including mental health disparities, health care provider mistrust, effective patient communication, and the interplay of these factors in the postanesthesia care unit. Finally, recommendations to improve TGD perioperative care are reviewed through an organizational approach with an emphasis on TGD-focused medical education. These factors are discussed through the lens of patient affirmation and advocacy with the intent to educate the anesthesia professional on the perioperative management of TGD patients.

Classroom Instruction: Medical Students' Attitudes Toward LGBTQI+ Patients.

The Association of American Medical Colleges declared it essential that medical students receive instruction on the health needs of lesbian, gay, bisexual, transgender, questioning, and intersex (LGBTQI+) individuals. The integration of LGBTQI+ health and instruction in medical curricula, however, is scant. A pre-post confidential survey study was completed by first-year medical students (N = 103; 85% response rate) in the context of classroom instruction. The California State University Northbridge instrument assessed students' perspectives on LGBTQI+ Patient-Care, Comfort with LGBTQI+ Patient Interactions, Gender and Sexuality, Civil Rights, and LGBTQI+ Education. Post-instruction, students reported a significant increase in understanding of bisexuality (p = .02), being transgender (p = .006), and LGBTQI+ couples' adoption rights (p = .003). The findings support the incorporation of LGBTQI+ instruction into medical curricula and suggest that educators may consider consulting pre-intervention data before teaching LGBTQI+ health content, which would allow material to be tailored toward learner-specific needs.

Predicting Drug Response and Synergy Using a Deep Learning Model of Human Cancer Cells.

Most drugs entering clinical trials fail, often related to an incomplete understanding of the mechanisms governing drug response. Machine learning techniques hold immense promise for better drug response predictions, but most have not reached clinical practice due to their lack of interpretability and their focus on monotherapies. We address these challenges by developing DrugCell, an interpretable deep learning model of human cancer cells trained on the responses of 1,235 tumor cell lines to 684 drugs. Tumor genotypes induce states in cellular subsystems that are integrated with drug structure to predict response to therapy and, simultaneously, learn biological mechanisms underlying the drug response. DrugCell predictions are accurate in cell lines and also stratify clinical outcomes. Analysis of DrugCell mechanisms leads directly to the design of synergistic drug combinations, which we validate systematically by combinatorial CRISPR, drug-drug screening in vitro, and patient-derived xenografts. DrugCell provides a blueprint for constructing interpretable models for predictive medicine.

Management of pediatric laryngeal webs secondary to severe croup and traumatic intubation.

Laryngotracheobronchitis is a common, typically self-limiting viral infection. However, severe laryngotracheobronchitis can require urgent intubation to prevent imminent airway obstruction. The concurrent inflammation and urgency make laryngeal trauma more likely. We report two cases of children who underwent emergent intubation for acute respiratory distress due to viral laryngotracheobronchitis and subsequently developed anterior laryngeal webs. Both underwent laryngoplasty with keel placement, with resolution of their laryngeal webs. These cases describe pediatric laryngeal web formation as a rare complication of traumatic intubation and a novel technique for endoscopic keel placement.

Use of Emergency Manuals to Treat Intraoperative Supraventricular Tachycardia and Hypotension During Exploratory Laparotomy.

Although intraoperative tachyarrhythmias are relatively common, their appropriate management is pertinent to reducing morbidity and mortality. In certain clinical scenarios, the initial steps of managing intraoperative tachyarrhythmias may be ambiguous. Emergency manuals (EMs) are cognitive aids that improve the outcome of critical events by providing current, medically established guidelines on management. The case of a patient with an intraoperative supraventricular tachycardia with narrow, irregular QRS complexes and refractory hypotension is described here. Relevant sections of Stanford Anesthesia Emergency Manual were activated immediately and guided the anesthesiologists in treating the patient's arrhythmia. The utilization of an EM allowed rapid selection of a pharmacologic agent that achieved hemodynamic stability. EMs allow healthcare providers to respond more appropriately and efficiently during critical events and thus directly improve patient care.

A Case of Pulmonary Cement Embolism Managed through Symptomatic Treatment.

OBJECTIVE: This case describes symptomatic pulmonary cement embolism as a rare postvertebroplasty complication and highlights its critical yet ill-defined management. BACKGROUND: Pulmonary cement embolism (PCE) is a feared complication of vertebroplasty in the treatment of vertebral fractures. While the majority of PCEs are asymptomatic, symptomatic PCEs often present with chest pain, tachycardia, signs of severe respiratory distress, and death. Computer tomography angiogram (CTA) allows visualization of cement within the pulmonary vasculature. Despite the well-established risk of PCE, clinical management is unclear with limited research on treatment options. Reported treatments include anticoagulation, embolectomy, CPR, and supportive care and observation. Report. We report the case of a 75-year-old woman who experienced shortness of breath, tachypnea, tachycardia, hypertension, and hypoxemia five days following a corrective surgery for a compression fracture of L3 with pedicle screw fixation, fusion of L2 through L4, and L2 vertebral body cement augmentation with polymethyl methacrylate. RESULTS: Breath sounds were diminished bilaterally with respiratory alkalosis and hypoxemia evident on arterial blood gas. CTA revealed intravasated cement throughout the right lung, including the pulmonary artery and upper and middle lobar arteries. The proposed mechanism is embolization of cement particles from the lumbar veins, which also showed intravasation. Due to the inorganic nature of the occluding material, the use of a thrombolytic agent was ruled against. Treatment included bronchodilators, 3 L of oxygen via nasal cannula, and prophylactic antibiotics, pulmonary toilet, and incentive spirometry. Symptomatic management was continued until she was discharged from the hospital in a stable condition. CONCLUSIONS: Postvertebroplasty pulmonary cement embolisms can be managed conservatively, without the use of anticoagulant or thrombolytic agents. This case illustrates a variation of care for this rare presentation and adds to the sparse literature on the management of PCEs.

A Case of Reverse Takotsubo Cardiomyopathy Incited by a Spinal Subdural Hematoma.

Takotsubo cardiomyopathy is a rare syndrome of transient, reversible left ventricular systolic dysfunction. It mimics myocardial infarction clinically and includes elevated cardiac enzymes, but echocardiography reveals apical ballooning and basal hyperkinesis. Infrequently, midventricular or even reverse Takotsubo patterns have been described, involving ballooning of the basal heart without the characteristic 'Takotsubo' appearance. There are cases in the literature that support a connection between reverse Takotsubo cardiomyopathy (r-TTC) and neurological insults as inciting factors. We report a case of r-TTC in an otherwise healthy 23-year-old man presenting with back pain, urinary retention, bradycardia, and hypertension. Troponin levels and brain natriuretic peptide (BNP) were elevated, and echocardiogram revealed an ejection fraction (EF) of less than 20%. In addition, MRI demonstrated a spinal subdural hematoma from T1-S1 with no cord compression. Repeated echocardiogram demonstrated an EF of 20-25% with a reverse Takotsubo pattern of cardiomyopathy. With supportive care, his clinical picture improved with normalization of cardiac enzyme and BNP values. This case represents a r-TTC presenting as heart failure in a young, apparently healthy male likely incited by a spinal subdural hematoma. To our knowledge, it is the first of its kind reported.

Best Location and Reader Role in Usage of Emergency Manuals During Critical Events: Experienced Emergency Manual Users' Opinion.

Introduction Emergency manuals (EM) are an essential component of the response to critical events by healthcare providers, and there is strong evidence to support the benefits of utilizing EMs in crisis management. Despite the widespread utilization of EMs by providers, there is currently no national standardized protocol for EM usage, accompanied by a deficit in research on EM usage. To develop a protocol for EM utilization, factors such as the best location for EMs to be placed and the EM reader role must be determined. Methods Anesthesiologists with experience in EM use from seven hospitals participated in a survey questionnaire that was distributed to all participants through WeChat using the WenJianxen software. Survey response numbers were converted into percentages and were used to summarize the categorical variables. Results Results showed the best location of EMs used during critical events was in the anesthesia station of the operating room and that the preferred reader of EMs during critical events is the senior physician. Conclusion Our study suggests that placing EMs within close reach of the health care providers may be most efficient and that the reader of EMs should be the leader of the clinical team. These results may be applicable to the development and implementation of a national protocol for EM usage.

Improving Ambulation and Minimizing Disability with Therapeutic Plasma Exchange in a Stiff-person Syndrome Patient with Recurrent Falls.

Stiff-person syndrome (SPS) is a rare, autoimmune, neuromuscular disorder that manifests with axial and proximal muscle stiffness, rigidity, and painful muscle spasms, often causing progressive disability due to limited movement. First-line therapies comprise symptomatic management with γ-aminobutyric acid-modulating drugs such as benzodiazepines and baclofen. Patients resistant to these treatments are often given intravenous immunoglobulin (IVIg). Severe disease refractory to first-line therapy and IVIg may be treated with therapeutic plasma exchange (TPE) or immunomodulatory agents such as rituximab. Current evidence derived from case reports and case series has shown that roughly half of SPS patients treated with TPE report benefits. Here, we report the case of a 68-year-old man with a 20-year history of severe SPS and recurrent falls who was admitted to the emergency department for a traumatic hip fracture. He had significant rigidity in the axial and extremity muscles with persistent spasms of the quadriceps femoris muscle. Postoperatively, he was unable to participate in physical therapy (PT) due to these symptoms. He previously failed treatment with diazepam, baclofen, and monthly IVIg. Under our care, he underwent seven TPE treatments. By the end of treatment, he reported significant improvement in mobility with a resolution of muscle spasms and was able to be discharged to inpatient rehabilitation. This suggests that TPE may offer an effective, safe treatment modality for patients with severe refractory SPS that may significantly improve mobility and disability associated with the disease.

Disruption of NSD1 in Head and Neck Cancer Promotes Favorable Chemotherapeutic Responses Linked to Hypomethylation.

Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) represents a distinct classification of cancer with worse expected outcomes. Of the 11 genes recurrently mutated in HNSCC, we identify a singular and substantial survival advantage for mutations in the gene encoding Nuclear Set Domain Containing Protein 1 (NSD1), a histone methyltransferase altered in approximately 10% of patients. This effect, a 55% decrease in risk of death in NSD1-mutated versus non-mutated patients, can be validated in an independent cohort. NSD1 alterations are strongly associated with widespread genome hypomethylation in the same tumors, to a degree not observed for any other mutated gene. To address whether NSD1 plays a causal role in these associations, we use CRISPR-Cas9 to disrupt NSD1 in HNSCC cell lines and find that this leads to substantial CpG hypomethylation and sensitivity to cisplatin, a standard chemotherapy in head and neck cancer, with a 40% to 50% decrease in the IC50 value. Such results are reinforced by a survey of 1,001 cancer cell lines, in which loss-of-function NSD1 mutations have an average 23% decrease in cisplatin IC50 value compared with cell lines with wild-type NSD1Significance: This study identifies a favorable subtype of HPV-negative HNSCC linked to NSD1 mutation, hypomethylation, and cisplatin sensitivity. Mol Cancer Ther; 17(7); 1585-94. ©2018 AACR.

A global transcriptional network connecting noncoding mutations to changes in tumor gene expression.

Although cancer genomes are replete with noncoding mutations, the effects of these mutations remain poorly characterized. Here we perform an integrative analysis of 930 tumor whole genomes and matched transcriptomes, identifying a network of 193 noncoding loci in which mutations disrupt target gene expression. These 'somatic eQTLs' (expression quantitative trait loci) are frequently mutated in specific cancer tissues, and the majority can be validated in an independent cohort of 3,382 tumors. Among these, we find that the effects of noncoding mutations on DAAM1, MTG2 and HYI transcription are recapitulated in multiple cancer cell lines and that increasing DAAM1 expression leads to invasive cell migration. Collectively, the noncoding loci converge on a set of core pathways, permitting a classification of tumors into pathway-based subtypes. The somatic eQTL network is disrupted in 88% of tumors, suggesting widespread impact of noncoding mutations in cancer.

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies.