In vitro modulator responsiveness of 655 CFTR variants found in people with cystic fibrosis.

BACKGROUND: In 2017, the US Food and Drug Administration initiated expansion of drug labels for the treatment of cystic fibrosis (CF) to include CF transmembrane conductance regulator (CFTR) gene variants based on in vitro functional studies. This study aims to identify CFTR variants that result in increased chloride (Cl-) transport function by the CFTR protein after treatment with the CFTR modulator combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA). These data may benefit people with CF (pwCF) who are not currently eligible for modulator therapies. METHODS: Plasmid DNA encoding 655 CFTR variants and wild-type (WT) CFTR were transfected into Fisher Rat Thyroid cells that do not natively express CFTR. After 24 h of incubation with control or TEZ and ELX, and acute addition of IVA, CFTR function was assessed using the transepithelial current clamp conductance assay. Each variant's forskolin/cAMP-induced baseline Cl- transport activity, responsiveness to IVA alone, and responsiveness to the TEZ/ELX/IVA combination were measured in three different laboratories. Western blots were conducted to evaluate CFTR protein maturation and complement the functional data. RESULTS AND CONCLUSIONS: 253 variants not currently approved for CFTR modulator therapy showed low baseline activity (<10 % of normal CFTR Cl- transport activity). For 152 of these variants, treatment with ELX/TEZ/IVA improved the Cl- transport activity by ≥10 % of normal CFTR function, which is suggestive of clinical benefit. ELX/TEZ/IVA increased CFTR function by ≥10 percentage points for an additional 140 unapproved variants with ≥10 % but <50 % of normal CFTR function at baseline. These findings significantly expand the number of rare CFTR variants for which ELX/TEZ/IVA treatment should result in clinical benefit.

Iatrogenic Facial Nerve Injury in Head and Neck Surgery in the Presence of Intraoperative Facial Nerve Monitoring With Electromyography: A Systematic Review.

The facial nerve is the seventh of 12 cranial nerves found in the head and neck region that facilitates several nerve fibers and pathways to perform various functions. Iatrogenic facial nerve injury during surgeries of the head and neck is common, ranging from 4-6%, particularly in procedures that involve mobilization or resection of associated anatomical structures. Any injury to the facial nerve or its branches impacts the quality of life and patient satisfaction as the degree of iatrogenic injury may result in partial or complete facial nerve paralysis. Of the various implementable techniques available to avoid injury, electromyography (EMG) has recently been widely used to monitor facial nerve function intraoperatively to determine the degree of injury and predict postoperative weakness. The purpose of this study was to analyze and review existing scientific literature in determining the role of intraoperative facial nerve monitoring (IFNM) with EMG in decreasing the incidence and degree of intraoperative facial nerve injury among commonly performed surgeries involving the facial nerve. A systematic review was conducted from articles published between September 2006 and December 2022. Suitable articles were identified from the MEDLINE/PubMed databases using relevant terms to meet the inclusion criteria. Articles were subsequently coded based on the inclusion/exclusion criteria as well as the type of surgery performed with concurrent use of EMG and the results from intraoperative monitoring. A total of 47 articles were found in relation to the use of IFNM, including studies to reduce the incidence and determine preventative measures to decrease nerve injury. Eleven articles were used to evaluate the use of EMG during various head and neck surgeries in decreasing the incidence of intraoperative facial nerve injury. Sources found were primarily divided based on the type of surgery performed when determining the use of EMG. Four sources tested the efficacy of EMG during parotidectomy, four sources during vestibular schwannoma resection, two sources during cochlear implant surgeries, and one during a lymphatic malformation surgery. IFNM also decreased the duration of surgery, the severity of facial nerve palsy, and the average time of facial nerve paralysis recovery. IFNM was found to not significantly predict facial nerve injury in the setting of intraoperative nerve injury but tended to preserve potential facial nerve function in vestibular schwannoma cases. The surgical setting determined the efficacy and use of IFNM in decreasing the incidence of facial nerve weakness and paralysis. IFNM had the best preventative and prognostic value when used in vestibular schwannoma resection, and the least in cochlear implants, with mixed evidence seen in the setting of parotidectomy. Overall, IFNM using EMG as an adjunct during surgery may reduce the risk of iatrogenic injury; however, additional studies must be performed to determine the degree of long-term patient satisfaction and quality of life achieved in the setting of IFNM.

Osteopathic Manipulative Treatment for a Chronic Rotator Cuff Tear: A Case Report.

Rotator cuff tears, particularly involving the supraspinatus muscle and/or tendon, are highly prevalent among individuals engaged in repetitive shoulder motions. Occupations demanding constant and repetitive shoulder movements are especially susceptible to rotator cuff injuries, potentially leading to prolonged joint wear and tear and an increased likelihood of joint replacement. Considering the impact of social determinants of health, including access to healthcare and socioeconomic status, it is imperative to explore conservative treatment modalities that alleviate financial burdens and reduce lengthy recovery periods. In this report, we present a case of a 64-year-old female hairdresser diagnosed with a chronic partial thickness rotator cuff tear who remained unresponsive to physical therapy and chiropractic manipulation but exhibited improvement following osteopathic manipulative treatment. Additionally, osteopathic considerations and pertinent literature are reviewed to provide insight into the broader context of shoulder pain management.

Probable drug-induced clitoral priapism due to potentiating effects of pregabalin and duloxetine.

PURPOSE: The following case report discusses probable clitoral priapism secondary to duloxetine and pregabalin. While this is a rare adverse effect, it is possible given the mechanism of action and potentiating effects of the combined therapy. This adverse drug reaction was reported to MedWatch and shows that additional research into the physiology of clitoral erection is warranted given the scarcity of information on how drugs influence this reaction. SUMMARY: A 53-year-old African American female with uncontrolled anxiety was started on duloxetine. Pregabalin was added 1 month later due to continued feelings of anxiety. Three weeks later, the patient reported symptoms of clitoral pain, as well as a swollen, tender, and erect clitoris. These adverse effects remained for 4 days, prompting the patient to present to the emergency department where a physical exam was completed with no significant finding except as noted above. Pregabalin was immediately discontinued by the attending physician based on the probability that the swelling was likely drug-induced clitoral priapism. During follow-up, the patient continued to note clitoral erection and pain. The psychiatric pharmacist tapered off duloxetine over 2 weeks with resolution of symptoms. In an examination of the mechanism of action of both drugs, pregabalin can amplify duloxetine's inhibitory effects on voltage-dependent calcium channels. It is likely this mechanism that causes smooth muscle relaxation and led to clitoral priapism. CONCLUSION: This case suggests that pharmacological agents affecting vasoconstriction through serotonergic receptors or calcium-dependent channels can also influence clitoral erection.

Screening for Hypertrophic Obstructive Cardiomyopathy in Patients With Panic Disorder: A Case Report.

Hypertrophic obstructive cardiomyopathy (HOCM) is a cardiovascular disease that is widely recognized as an important cause of various cardiovascular pathologies. Passed through an autosomal dominant inheritance pattern, mutations can result in cardiac dysfunction that can manifest in dyspnea, exercise intolerance, and sudden death. Panic disorder can present similarly to HOCM; however, precautions and treatment differ significantly. Here, we present a case of a 56-year-old male with a history of panic disorder who presented to the emergency department with recurrent episodes of palpitations, lightheadedness, and dyspnea, and who was subsequently hospitalized due to new ventricular tachyarrhythmia and diagnosed with HOCM. This case highlights the importance of detailed history taking, follow-up of chronic symptoms, and consideration of genetic screening for HOCM in patients with panic disorder.

Abortion Is a Right: Perspectives of Family Medicine Physician Residents.

Abortion is healthcare. Bodily autonomy is a fundamental human right. As chief resident physicians representing family medicine residency programs in the Greater Bay Area and Central California in the University of California San Francisco Family Medicine Alliance, we share a deep commitment to promoting health equity, advancing social justice, and eliminating health disparities. The 2022 Supreme Court decision in Dobbs v. Jackson Women's Health Organization to overturn Roe v. Wade contradicts the inherent rights of patients to make their own reproductive healthcare decisions. This is a clarion call for all people to engage in activities to raise awareness and prompt discussion about abortion, reproductive rights, and maternal mortality.

Inhibiting the Musculoskeletal Pathological Processes in Post-knee Replacement Surgery With Osteopathic Manipulative Treatment: A Systematic Review.

Total knee arthroplasty (TKA) is a very common surgical treatment approach for severe osteoarthritis. Complications of TKA include loss of range of motion and prolonged analgesic requirement for pain control. Osteopathic manipulative techniques (OMT) have been utilized to address localized muscular stiffness to improve range of motion; however, limited studies directly correlate OMT and TKA recovery. This review highlights the therapeutic benefits OMT can have in the postoperative management of arthroplasty with respect to range of motion, edema, pain perception, and ability to perform activities of daily living. This review revealed the use of OMT would positively influence range of motion by manipulation of localized musculature and can result in decreased demand for analgesics. This can, in turn, shorten hospital stay and return the ability of patients to perform activities of daily living earlier than without OMT. Increased research is needed to strengthen these findings on the benefits of OMT in the postoperative management of arthroplasty.

Assessing the Knowledge of the Osteopathic Profession in New York City's Eastern European Communities.

Background According to the decennial Osteopathic Survey of Healthcare in America, the osteopathic profession has been steadily gaining recognition in the United States, particularly among the White/Caucasian demographic. This, however, does not take into account immigrant European communities that, while racially classified as White/Caucasian, may be unexposed to osteopathic physicians (DOs) in their home country and may be reticent to osteopathic manipulative medicine. Data on non-English-speaking communities are limited and can mask the need for further outreach. This study aimed to identify literature in osteopathic outreach to minority communities and assess osteopathic awareness in New York City's Eastern European communities. Secondary objectives include characterization of potential barriers in hindering access to osteopathic medicine, and, by extension, other minority groups. Methodology An anonymous survey prepared in Russian and English was used to gather demographics, education level, healthcare habits, and knowledge of the osteopathic profession. To provide a clinical scenario, a health habit question regarding low back pain (LBP) was provided to participants. Participants over the age of 18 were randomly selected from high density Eastern European areas at two separate time points. Statistical analysis was performed using R to evaluate independence between questions using chi-square tests. Results A total of 150 surveys met the inclusion criteria, with 71 males and 79 females, an age range of 18-92, and a median age of 62. On comparing demographics, education level, and healthcare habits, only English proficiency showed statistical significance (p = 0.039) in determining recognition of the osteopathic profession. Overall, 60% (n = 94) stated that they have heard of osteopathic medicine and knew what a DO physician does. However, only 35% (n = 53) would see a DO for LBP, with 50% (n = 77) seeing a physical therapist. Conclusions Compared to research examining osteopathic awareness in ethnic minority communities, the Russian community in New York appears to have greater recognition of the osteopathic profession. This, however, does not translate into a clinical scenario as more participants were more likely to see a physical therapist. While this difference can be attributed to numerous factors, it stands without doubt that greater osteopathic outreach and data collection needs to be performed in minority communities.

Retained Copper Intrauterine Device Fragment in Pregnancy: A Case Report.

Copper intrauterine device (IUD) failure and fragmentation are rare, with minimal documentation on their effects in pregnancy. Recommendations from professional organizations highlight the importance of prompt identification and surgical removal, as case reports have noted various acute and chronic intra-abdominal pathologies. However, limited guidance exists around counseling patients who are pregnant with a retained IUD fragment. Here, we present a case of a normal pregnancy with a retained copper IUD fragment, while reviewing existing data on management and counseling.

Epiploic Appendagitis Mimicking Acute Appendicitis: An Osteopathic Case Report.

Acute epiploic appendagitis is a rare cause of abdominal pain, often misdiagnosed as acute appendicitis or diverticulitis given similar clinical presentation and findings. The treatment is supportive care and is typically self-limited. The osteopathic structural exam can give insight into pathology and in this case, was suggestive of a non-appendiceal origin of her pain, in which emergent surgery could be avoided. Requiring computerized tomography to identify, acute epiploic appendagitis is a rare cause of abdominal pain and should be considered in the differential diagnosis.

Obesity Hypoventilation Syndrome-Related Challenges in Acute Respiratory Failure.

Obesity hypoventilation syndrome (OHS) is a condition commonly found in severely obese patients in which they fail to breathe deeply or rapidly enough to offset the body's need for oxygen consumption and carbon dioxide release. This report presents a case of a 49-year-old super-super-morbid obese female with a body mass index (BMI) of 90 kilogram per meter squared (kg/m²), chronic obstructive pulmonary disease (COPD), and end-stage cor pulmonale, who was brought to the emergency department for altered mental status and requiring emergent airway due to respiratory failure secondary to OHS. The continued increase in rates of obesity worldwide, especially in those with BMI ≥ 50 kg/m², may lead to an increase in the incidence of OHS. With comorbidities secondary to obesity and associated complexity, this medically challenging case emphasizes the need for refined management strategies in caring for OHS in super-super-morbidly obese patients.

Complications of COVID-19 Pneumonia and Multiple Sclerosis Exacerbation.

Multiple sclerosis (MS) is the most common autoimmune disease in the United States, in which demyelination of the brain and spinal cord disrupts the transmission of signals throughout the body. With an average life expectancy of 30 years from the start of the disease, treatment relies on symptom management through steroids and disease-modifying agents, as there is no cure. While MS patients have not been shown to be at increased risk for coronavirus disease 19 (COVID-19) infection, prolonged hospitalizations and severe COVID-19 sequelae have been linked to various MS subgroups. Limited studies, however, have reported on the role of COVID-19 in precipitating MS exacerbations, as flare-ups often occur during times of stress or immunological insult. Here we present a 45-year-old patient with relapsing-remitting multiple sclerosis whose neurological symptoms worsened sharply in the weeks following an inpatient admission for COVID-19 pneumonia.

Undergraduate Medical School Health Fair Hepatitis Screenings: Utilizing Non-Profit Community Organizations.

BACKGROUND: Undergraduate medical schools serve a critical role in providing screenings to medically underserved populations through the use of health fairs. Non-profit community organizations (NPCO) often participate by providing local credibility, administrative resources, and technical knowledge. Here we present a three-year narrative of hepatitis B and C screening efforts to highlight the challenges and benefits of undergraduate medical school and NPCO partnerships. METHODS: Hepatitis screenings were conducted at biannual health fairs in Harlem, New York from 2017 to 2019. Meeting minutes from post-event debriefings were analyzed to identify any overarching themes with NPCOs. RESULTS: NPCOs share a common goal in working with the community to advance their access to medical care and treatment. Communication and prompt follow-up are critical to maintaining expectations between NPCOs and health fair organizers. CONCLUSIONS: NPCOs can play an important role in encouraging, outreaching, and even managing hepatitis screening initiatives in conjunction with medical school health fairs.

Clinical Detection of Primary Pulmonary Angiosarcoma.

Pulmonary angiosarcomas (PAS) are rare malignant vascular tumors that due to their aggressive and metastatic nature, are often diagnosed at a late stage, resulting in a poorer prognosis. Here we present a 53-year-old male who was initially found to have recurring episodes of dyspnea and syncope, with initial workup showing bilateral saddle pulmonary embolisms on computerized tomography, presumed secondary to newly discovered atrial fibrillation with sinus node dysfunction. Further investigation over subsequent months and subsequent biopsy of a potential lung mass ultimately revealed pulmonary angiosarcoma of the spindle cell line. This case emphasizes findings in the current literature, which reveal the time between the onset of symptoms and definitive diagnosis ranges from two to six months, with a median survival time of seven months or two months, with solitary lesions or multiple lesions at the time of diagnosis, respectively. With the limited incidence of PAS, this case suggests benefits in the development of screening and detection criteria for earlier detection and treatment.

Combating Diagnostic Delay of Endometriosis in Adolescents via Educational Awareness: A Systematic Review.

Endometriosis occurs in approximately 10% of adult women worldwide; however, it is commonly under- or misdiagnosed in adolescents. The purpose of this study was to analyze existing scientific literature for reasons for diagnostic delay of endometriosis and to determine how education regarding endometriosis could be improved. An integrative review was conducted based on articles published between December 1980 and December 2020. Suitable articles were identified from the MEDLINE/PubMed databases, using relevant terms. Eligible studies included discussion on potential causes of diagnostic delay of endometriosis in the adolescent population. Data were extracted from eligible publications and qualitative synthesis was used. The 27 articles included in the study revealed several primary reasons for the delay, such as a physician and/or patient knowledge gap, normalization by physician and patient, lack of research, and physician resistance. Strategies to lessen diagnostic delay of endometriosis in adolescents must include integrated actions by educators and healthcare providers to improve health literacy and awareness of common causes of pelvic pain in this age group.

Influenza Vaccination Quality Improvement as a Model for COVID-19 Prophylaxis.

INTRODUCTION: Many comparisons have been made on the effect and impact of COVID-19 on influenza pandemics of history. Therefore, it is reasonable to infer that the strategies utilized by healthcare providers to improve influenza vaccination rates can similarly be applied to the administration of a COVID-19 vaccine. The purpose of this study was to determine the rationale of low influenza vaccination rates in an urban allergy clinic and how to improve patient education and knowledge regarding the importance of influenza vaccination. A three-year comparison of interventions is presented as well as its application to future COVID-19 vaccinations. METHODS: This study was performed at an outpatient allergy and clinical immunology practice (MSBI) with hospital affiliation in New York City, New York. A quality improvement medical committee was formed to optimize influenza vaccination rates to greater than 71% and established standardized protocols regarding patient intake workflows, vaccine counseling, and documentation. Patient records from four providers were used for this study to compare pre-and post-intervention rates. RESULTS: 984 patients met inclusion criteria, with a normal distribution of ages (18-80), race, and sex. Average vaccination rates prior to the intervention were 9.25-13.60%. The average vaccination rate after the intervention was 91.34%. DISCUSSION: The MSBI quality improvement study identified key areas to address in improving influenza vaccination rates. Vaccine hesitancy, public misinformation, and ambivalence surrounding vaccination with egg allergies or during a subcutaneous immunotherapy injection were all topics addressed during the 2018-2019 intervention year. Additional attention was also put toward provider education and standardization of documentation. Shared decision making and intensive education/outreach efforts are needed by physicians and patients alike to overcome vaccine hesitancy. In comparing this to upcoming COVID-19 vaccine challenges, similar barriers will likely also need to be addressed. Greater research is needed to understand patient motivations regarding hesitancy specific to the COVID-19 vaccine. CONCLUSION: As evidenced in the yearly battle with influenza and now the COVID-19 pandemic, it has become essential to identify and implement multi-level strategies to maximize vaccination rates, especially amid a global pandemic. With COVID-19 vaccines reaching emergency approval stages, it is important for healthcare providers to start creating workflows and strategies to address patient inquiries. The influenza vaccination quality improvement project presented here can be used as a guideline for future evaluations of COVID-19 vaccination efforts.

Utility of Serum Biomarker Indices for Staging of Hepatic Fibrosis Before and After Venesection in Patients With Hemochromatosis Caused by Variants in HFE.

BACKGROUND & AIMS: Hemochromatosis that is associated with variants in the homeostatic iron regulator gene (HFE) is characterized by intestinal absorption of iron and excessive body and hepatic iron stores; it can lead to hepatic fibrosis and cirrhosis. Fibrosis has been staged by analysis of liver biopsies, but non-invasive staging methods are available. We evaluated the ability of aspartate aminotransferase:platelet ratio index (APRI), the fibrosis-4 (FIB-4) index, and gamma-glutamyl transferase:platelet ratio (GPR) to assess hepatic fibrosis staging in subjects with HFE-associated hemochromatosis, using liver biopsy-staged fibrosis as the reference standard. METHODS: We performed a retrospective, cross-sectional analysis of 181 subjects with HFE-associated hemochromatosis and hepatic fibrosis staged by biopsy analysis and available serum samples. We calculated APRI, FIB-4, and GPR at diagnosis for all 181 subjects and following venesection therapy in 64 of these subjects (7 subjects had follow-up biopsy analysis). We used area under the receiver operating characteristic curve (AUROC) analysis to assess the relationships between APRI score, FIB-4 score, and GPR and advanced (F3-F4) fibrosis and to select cut-off values. RESULTS: Hepatic fibrosis stage correlated with APRI score (r = 0.54; P < .0001), FIB-4 score (r = 0.35; P < .0001), and GPR (r = 0.36, P < .0001). An APRI score above 0.44 identified patients with advanced fibrosis with an AUROC of 0.88, 79.4% sensitivity, 79.4% specificity, and 81% accuracy. A FIB-4 score above 1.1 identified patients with advanced fibrosis with an AUROC of 0.86, 80% sensitivity, 80.3% specificity, and 81% accuracy. A GPR above 0.27 identified patients with advanced fibrosis with an AUROC of 0.76, 67.7% sensitivity, 70.3% specificity, and 69% accuracy. APRI score was significantly more accurate than GPR (P = .05) in detecting advanced fibrosis; there was no difference between APRI and FIB-4. Venesection treatment was associated with significant reductions in APRI (P < .0001) and GPR (P < .001), paralleling fibrosis regression observed in available liver biopsies. Post-venesection APRI identified 87% of subjects with advanced fibrosis that decreased to levels that indicate stage F1-F2 fibrosis. CONCLUSIONS: In a retrospective study of 181 subjects with HFE-associated hemochromatosis, we found that APRI and FIB-4 scores identified patients with advanced hepatic fibrosis with 81% accuracy. APRI scores might also be used to monitor fibrosis regression following venesection.

Further Reduction in Help-Seeking Behaviors Amidst Additional Barriers to Mental Health Treatment in Asian Populations: A Contemporary Review.

Under diagnosis and treatment of mental health illnesses lead to chronic presentations and consequences. Multiple factors contribute to gaps in treatment, including the role culture plays in the development or suppression of help-seeking behaviors (HSBs). In the Asian community, conversation and recognition of mental health and its disorders are considered shameful. This review presents an analysis of literature to identify barriers to mental health treatment pronounced in Asian populations and discusses how culture influences these barriers and treatment-seeking behaviors, particularly in the context of the Asian-origin Coronavirus disease 2019 (COVID-19) global pandemic. It is the purpose of this review to discuss Asian American underutilization of mental health services and understand the factors the contribute to psychiatric care resistance in Asian communities.

Providing Culturally Competent Care for COVID-19 Intensive Care Unit Delirium: A Case Report and Review.

Coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in March 2020. Caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, its high transmissibility required infected individuals to be placed in negative pressure isolation rooms when admitted to intensive care units (ICU). Studies have shown that limited social support can increase the risk of developing delirium during ICU stays. Minimal research exists on COVID-19-associated ICU delirium as hospitals and government organizations focus on combating equipment shortages and case surges. Here, we present the case of a 64-year-old Filipino male with COVID-19 ICU delirium status post-intubation and ventilation. His hospital course was complicated by the medical staff's assumption that the patient spoke Spanish and improved after being assigned a Tagalog-speaking nurse who facilitated family communication. This case highlights the importance of cultural competency and communication in the management of COVID-19 associated ICU delirium. In particular, Filipino cultural practices and their intersection with healthcare in the larger context of providing culturally competent care are highlighted. The use of culturally competent care serves to assure the use of appropriate services and reduces the occurrence of medical errors due to misunderstandings caused by differences in language or culture. Familial involvement is critical for ICU delirium; however, the COVID-19 pandemic has required healthcare providers to think beyond conventional means. The use of technology to virtually communicate with family also serves as a helpful tool to treat signs of delirium. As seen in this case, a lack of understanding of the Filipino culture resulted in assumptions on the part of the healthcare provider which led to the prolongation of delirium in a COVID-19 ICU patient, but the correct utilization of cultural competence helped the patient recover successfully.