Inadequate Clearance Research Articles

P-34. Patients’ Survey of Human Papilloma Virus Vaccination among Systemic Lupus Erythematosus Patients in Japan after Suspension of Proactive Recommendation

Abstract Background Systemic lupus erythematosus (SLE) patients are known to have a high incidence of cervical cancer. The main reason for this is considered to reflect the high rate of Human papilloma virus (HPV) infection and inadequate HPV clearance due to immunosuppressive status. Japan has been facing a problem of low HPV vaccination rates due to the suspension of proactive recommendations for routine HPV vaccination for more than eight years because of the negative media campaign. The objective of this study is to identify the factors that inhibit HPV vaccination among SLE patients to develop strategies for improving HPV vaccination rate. Figure Sources of medical information for HPV vaccinated and unvaccinated participants. We asked which informational tools participants use to gather medical information. The most trusted sources are indicated by dark bars; others are indicated by light bars. * indicates significant differences between HPV vaccinated and unvaccinated participants (p<0.05, chi-square test). (a): Answers by HPV vaccinated participants. (b): Answers by HPV unvaccinated participants. HPV, Human papilloma virus; SNS, Social networking service; TV, Television Methods We conducted a questionnaire survey of female SLE patients aged 18-45 years attending our hospital to analyze factors related to HPV vaccination. Results We obtained responses of 83 participants. Only 5 (6.0%) were received HPV vaccination, 15 (18.1%) were uncertain of their vaccine history, and 27 (32.5%) had never even heard of HPV vaccination. The reasons for unvaccinated against HPV were "don't know" with 24 participants, "missed opportunity" with 15, and "troublesome, somehow" with 8. The most trusted source of medical information for the unvaccinated was their physician (47, 60.3%) (Figure). Among the unvaccinated, those who wished to be vaccinated in the future were positively correlated with “trust of vaccine benefit” (r=0.515. p=0.014) and “accurate knowledge about HPV vaccine” (r=0.614, p=0.002), and negatively correlated with “negative attitudes toward vaccination and vaccine policy” (r=-0.562, p=0.007). Conclusion HPV vaccination rate among SLE patients in Japan was extremely low. The main reason was lack of knowledge. The most effective solution is considered to provide accurate information and adequate recommendations of HPV vaccination by attending physicians. Disclosures Yoshiaki Gu, MD, PhD, MPH, MSD K.K.: Grant/Research Support

The intricate interplay between ferroptosis and efferocytosis in cancer: unraveling novel insights and therapeutic opportunities.

The complex interplay between ferroptosis and efferocytosis in cancer has attracted significant interest recently. Efferocytosis, the process of eliminating apoptotic cells, is essential for preserving tissue homeostasis and reducing inflammation. However, dysregulation of efferocytosis can have profound effects on cancer. Apoptotic cells accumulate because of impaired efferocytosis, which triggers chronic inflammation and the release of pro-inflammatory chemicals. Surprisingly, accumulating evidence suggests that dysregulation of ferroptosis- a form of controlled cell death characterized by lipid peroxidation and the buildup iron-dependent reactive oxygen species (ROS)-can influence efferocytic activities within the tumor microenvironment. Dysfunctional iron metabolism and increased lipid peroxidation, are associated with ferroptosis, resulting in inadequate apoptotic cell clearance. Conversely, apoptotic cells can activate ferroptotic pathways, increasing oxidative stress and inducing cell death in cancer cells. This reciprocal interaction emphasizes the complex relationship between efferocytosis and ferroptosis in cancer biology. Understanding and managing the delicate balance between cell clearance and cell death pathways holds significant therapeutic potential in cancer treatment. Targeting the efferocytosis and ferroptosis pathways may offer new opportunities for improving tumor clearance, reducing inflammation, and sensitizing cancer cells to therapeutic interventions. Further research into the interaction between efferocytosis and ferroptosis in cancer will provide valuable insights for the development of novel therapies aimed at restoring tissue homeostasis and improving patient outcomes.

Microbial Colonization Patterns and Prognostic Factors in Cystic Fibrosis Patients: A Comprehensive Assessment

Background: Cystic fibrosis (CF) is one of the most common autosomal recessive genetic disorders in pediatrics. Due to inadequate clearance of inhaled pathogens in the mucus, these organisms colonize the airways, leading to inflammatory responses. The microorganisms identified in sputum cultures of CF patients are critical for selecting the appropriate antibiotics for treatment. Objectives: The main aim of this study is to identify the microorganisms colonizing the sputum of patients with CF and to assess the prognostic factors influencing these colonizations. Methods: This study included all cases of CF patients referred to the pediatric pulmonology clinics at Mofid Pediatric Hospital between 2017 and 2022. Demographic and clinical history data were obtained from clinical records and face-to-face interviews. Sputum cultures were performed for all patients. The chi-square test was applied to identify significant differences in qualitative variables. For quantitative variables, the One-Way ANOVA and Student's t-test were used to find significant differences for parametric data. Results: A total of 206 patients participated in the study, with a mean age of 9.8 ± 5.42 years. Pseudomonas aeruginosa and Staphylococcus aureus were the most common microorganisms detected, with prevalence rates of 51.94% and 16.99%, respectively. Common microorganisms were more prevalent among patients with normal or below-normal Body Mass Index (BMI), while unusual microorganisms were more frequent in those with above-normal BMI, indicating a significant relationship between microorganism type and BMI (P-value: 0.014). Additionally, common microorganisms were more prevalent in older patients, with a mean age of 10.30 years (P-value = 0.006). No other variables showed statistical significance. Conclusions: Pseudomonas aeruginosa and Staphylococcus aureus were the most prevalent microorganisms in the sputum cultures of CF patients. A significant relationship was observed between microorganism type, BMI, and age of the patients.

Investigating Optic Nerve Sheath Diameter in Prone Position Spinal Surgery Patients: A Pilot Study.

This study aimed to evaluate the effect of intraoperative positioning and ocular immobility on the amount of cerebrospinal fluid around the optic nerve in patients undergoing prone spinal surgery by measuring the optic nerve sheath diameter (ONSD) using ultrasound. Consecutive participants (n = 15 patients, 30 eyes) were scanned preoperatively, intraoperatively approximately 20 minutes before the end of the surgery, and postoperatively in the post-anesthesia care unit at least 10 min after the completion of the surgery at one academic hospital. On average, patients who underwent prone spinal surgery had a 21% increase in ONSD intraoperatively, with a positive time-dependent relationship with the overall length of surgery (P 0.001). ONSDs postoperatively returned to baseline and were not significantly different from preoperative measurements. Our findings suggest pooling and inadequate clearance of perioptic cerebrospinal fluid during prone spinal surgery that improves following termination of the procedure and return of the patient to an upright position.

(023) PREVALENCE OF CLITORAL ADHESIONS AMONG PATIENTS UNDERGOING VESTIBULECTOMY FOR NEUROPROLIFERATIVE VESTIBULODYNIA

Abstract Introduction Previously we have reported that 23% of individuals with vulvas presenting to our sexual medicine clinic for various sexual dysfunctions demonstrated clitoral adhesions based on vulvoscopy with photography. Clitoral adhesions occur when the epithelial skin surfaces of the prepuce and glans clitoris become adherent, such that the corona is not fully visualized during full prepucial retraction. The severity of clitoral adhesions is best documented using vulvoscopy with photography and rated as mild, moderate or severe clitoral adhesions when >75%, 25-75%, and < 25% of the glans clitoris is visualized, respectively. (Figure 1) Clitoral adhesions are often associated with inadequate clearance of keratinaceous sloughed material from the epithelial surfaces of the prepuce and glans clitoris. This trapped material can form keratin pearls that result in local inflammation and glans hypersensitivity or pain. In the previous study, patients had mild (44%), moderate (34%), and severe (22%) clitoral adhesions. We observed clitoral adhesions in individuals who presented with entry dyspareunia, severe allodynia, and hyperalgesia and underwent complete vestibulectomy for clinically suspected neuroproliferative vestibulodynia (NPV). Patients could opt to have lysis of clitoral adhesions performed at the time of vestibulectomy. Objective We examined the association between clitoral adhesions and NPV. Methods A retrospective chart review of patients with NPV who underwent vestibulectomy and lysis of clitoral adhesions concomitantly between January 1, 2021 and May 31, 2024 was performed. History, physical examination, pre-op vulvoscopy with photographs, operative records and patient outcome data were collected. Results Eighty-eight patients with NPV, (mean age 29, range 19– 64 years), underwent vestibulectomy surgery. A total of 53 (60%) of these patients underwent concomitant lysis of mild (38%), moderate (49%), or severe (13%) clitoral adhesions. In 89% of cases, multiple keratin pearls were removed. Conclusions There is a high prevalence of clitoral adhesions in patients with NPV (60%) compared to the total population of individuals with vulvas who presented to our sexual medicine clinic for sexual concerns (23%). While clitoral adhesions are not always symptomatic, we hypothesize that the high prevalence in patients with NPV may be due one or more of the following: i) pain/stress resulting in peripheral nerves releasing neurotransmitters that stimulate proliferation/differentiation of prepucial sebaceous glands and upregulate prepucial sebaceous cell lipid synthesis, ii) infrequency of clitoral tissue engorgement from sexual activity, iii) limitation or aversion to touching or retracting clitoral prepucial tissue, iv) increased frequency of wearing menstrual pads rather than tampons, v) severe genital pain perceived as co-existing in both vestibule and clitoris and vi) surgery already scheduled for NPV so performing lysis of clitoral adhesions while under anesthesia was convenient. Clinicians should be aware of this high association. Disclosure No.

Left atrial strain assessment unveils left ventricular diastolic dysfunction in neonates with transient tachypnea of the newborn: A prospective observational study.

An inadequate clearance of lung fluid plays a key role in the pathogenesis of transient tachypnea of the newborn (TTN). To evaluate if left ventricular diastolic dysfunction contributes to reduced clearance of lung fluid in TTN. This was a prospective, observational study. Echocardiography and lung ultrasound were performed at 2, 24 and 48 h of life (HoL) to assess biventricular function and calculate lung ultrasound score (LUS). Left atrial strain reservoir (LASr) provided surrogate measurement of left ventricular diastolic function. Twenty-seven neonates with TTN were compared with 27 controls with no difference in gestation (36.1 ± 2 vs. 36.9 ± 2 weeks) or birthweight (2508 ± 667 vs. 2718 ± 590 g). Biventricular systolic function was normal in both groups. LASr was significantly lower in cases at 2 (21.0 ± 2.7 vs. 38.1 ± 4.4; p < 0.01), 24 (25.2 ± 4.5 vs. 40.6 ± 4.0; p < 0.01) and 48 HoL (36.5 ± 5.8 and 41.6 ± 5.2; p < 0.01), resulting in a significant group by time interaction (p < 0.001), after adjusting for LUS and gestational diabetes. A logistic regression model including LUS, birth weight and gestational diabetes as covariates, showed that LASr at 2 HoL was a predictor of respiratory support at 24 HoL, with an adjusted odds ratio of 0.60 (CI 0.36-0.99). LASr was reduced in neonates with TTN, suggesting diastolic dysfunction, that may contribute to the delay in lung fluid clearance.

(027) HIGH PREVALENCE OF SYMPTOMATIC CLITORAL ADHESIONS IN PATIENTS WITH NEUROPROLIFERATIVE VESTIBULODYNIA UNDERGOING VESTIBULECTOMY

Abstract Introduction Clitoral adhesions occur when the epithelial skin surfaces of the prepuce and glans clitoris become adherent. The severity of clitoral adhesions is best documented during full prepucial retraction using vulvoscopy with photography; mild, moderate, and severe clitoral adhesions occur when there is &amp;gt;75%, 25-75%, and &amp;lt;25% visualization of the glans clitoris, respectively. Clitoral adhesions are associated with a closed compartment with inadequate clearance of keratinaceous sloughed material from the epithelial surfaces of the prepuce and glans clitoris. This trapped material may form keratin pearls resulting in local inflammation and glans hypersensitivity/pain. In one study of 614 evaluable individuals with vulvas who presented to a sexual medicine clinic for various sexual dysfunctions, 23% demonstrated clitoral adhesions based on vulvoscopy with photography (mild 44%, moderate 34%, and severe 22%) of which 14% complained of clitoral hypersensitivity/pain. We observe symptomatic and asymptomatic clitoral adhesions occurring in women presenting with entry dyspareunia, severe allodynia and hyperalgesia, who are clinical suspected and pathologically conformed to have neuroproliferative vestibulodynia (NPV). Surgical management of the NPV involves complete vestibulectomy with vaginal advancement flap. For those patients who also have clitoral adhesions, lysis of clitoral adhesions may be performed at the time of vestibulectomy. Objective To examine the association between clitoral adhesions and NPV. Methods A retrospective chart review of patients with NPV who underwent vestibulectomy and lysis of clitoral adhesions concomitantly between January 1, 2021 and October 31, 2023 was performed. History, physical examination, pre-op vulvoscopy with photographs, operative records and patient outcome data were collected. Results Sixty-three patients with NPV, (mean age 29, range 19 – 64 years), underwent vestibulectomy surgery. A total of 34 (54%) of these patients underwent concomitant lysis of (mild (38%), moderate (50%), or severe (12%) clitoral adhesions. Multiple keratin pearls were removed in 91% of cases. More than half (53%) of these patients with NPV and clitoral adhesions complained of glans hypersensitivity/pain during pre-op vulvoscopy. The majority (88%) of this cohort reported “somewhat better” or “very much better” on PGI-I after lysis of adhesions. No negative side effects following the lysis of clitoral adhesions were noted. Conclusions There is a high prevalence of symptomatic clitoral adhesions in patients with NPV (53%) compared to women who presented to a sexual medicine clinic for other sexual concerns (14%). While clitoral adhesions are not always symptomatic, we hypothesize the high prevalence in patients with NPV may be due any of the following: i) pain/stress resulting in peripheral nerves releasing neurotransmitters that stimulate proliferation/differentiation of prepucial sebaceous glands and upregulate prepucial sebaceous cell lipid synthesis, ii) infrequency of clitoral tissue engorgement from sexual activity, iii) limitation or aversion to touching or retracting clitoral prepucial tissue, iv) increased frequency of wearing menstrual pads rather than tampons, v) severe genital pain perceived as co-existing in both vestibule and clitoris and vi) the patient is already scheduled for surgery under anesthesia so the patient conveniently agrees to also undergo lysis of adhesions. Clinicians should be aware of this high association. Disclosure No.

(068) HIGH PREVALENCE OF SYMPTOMATIC CLITORAL ADHESIONS IN PATIENTS WITH NEUROPROLIFERATIVE VESTIBULODYNIA UNDERGOING VESTIBULECTOMY

Abstract Introduction In a previous study of 614 evaluable individuals with vulvas who presented to our sexual medicine clinic for various sexual dysfunctions, 23% demonstrated clitoral adhesions based on vulvoscopy with photography. Clitoral adhesions occur when the epithelial skin surfaces of the prepuce and glans clitoris become adherent. The severity of clitoral adhesions is best documented during full prepucial retraction using vulvoscopy with photography; mild, moderate and severe clitoral adhesions occur when there is &amp;gt;75%, 25–75%, and &amp;lt; 25% visualization of the glans clitoris, respectively. Clitoral adhesions are associated with inadequate clearance of keratinaceous sloughed material from the epithelial surfaces of the prepuce and glans clitoris. This trapped material may form keratin pearls resulting in local inflammation and glans hypersensitivity/pain. In the previous study, patients had mild (44%), moderate (34%), and severe (22%) clitoral adhesions, with 14% patients having complaints of clitoral hypersensitivity/pain. In individuals who presented with entry dyspareunia, severe allodynia, and hyperalgesia who underwent complete vestibulectomy for clinically suspected neuroproliferative vestibulodynia (NPV), we observed both symptomatic and asymptomatic clitoral adhesions. Patients could opt to have lysis of clitoral adhesions performed at the time of vestibulectomy. Objective To examine the association between clitoral adhesions and NPV. Methods A retrospective chart review of patients with NPV who underwent vestibulectomy and lysis of clitoral adhesions concomitantly between January 1, 2021 and October 31, 2023 was performed. History, physical examination, pre-op vulvoscopy with photographs, operative records and patient outcome data were collected. Results Sixty-three patients with NPV, (mean age 29, range 19– 64 years), underwent vestibulectomy surgery. A total of 34 (54%) of these patients underwent concomitant lysis of mild (38%), moderate (50%), or severe (12%) clitoral adhesions. In 91% of cases, multiple keratin pearls were removed. More than half (53%) of these patients with NPV and clitoral adhesions complained of glans hypersensitivity/pain during pre-operative vulvoscopy. The majority (88%) of this cohort reported “somewhat better” or “very much better” on PGI-I after lysis of adhesions. No negative side effects following the lysis of clitoral adhesions were noted. Conclusions There is a high prevalence of symptomatic clitoral adhesions in patients with NPV (53%) compared to the total population of individuals with vulvas who presented to our sexual medicine clinic for sexual concerns (14%). While clitoral adhesions are not always symptomatic, we hypothesize that the high prevalence in patients with NPV may be due one or more of the following: i) pain/stress resulting in peripheral nerves releasing neurotransmitters that stimulate proliferation/differentiation of prepucial sebaceous glands and upregulate prepucial sebaceous cell lipid synthesis, ii) infrequency of clitoral tissue engorgement from sexual activity, iii) limitation or aversion to touching or retracting clitoral prepucial tissue, iv) increased frequency of wearing menstrual pads rather than tampons, v) severe genital pain perceived as co-existing in both vestibule and clitoris and vi) surgery already scheduled for NPV so performing lysis of clitoral adhesions while under anesthesia was convenient. Clinicians should be aware of this high association. Disclosure No.

Functionality and Usability of mHealth Apps in Patients with Peritoneal Dialysis: A Systematic Review.

mHealth has been utilized in the care of patients with chronic kidney disease, allowing the collection of patient health-related data, offering disease-related information, enabling the tracking and recording of biochemical parameters, and enabling communication with healthcare providers in real time through applications. mHealth may improve the health outcomes in patients with peritoneal dialysis. This systematic review aimed to summarize evidence regarding the functionality and usability of mHealth apps in patients with peritoneal dialysis. We conducted a comprehensive literature review, searching in five databases, including CINAHL, Cochrane, PsycINFO, PubMed, and Web of Science, to retrieve titles and abstracts related to peritoneal dialysis and mHealth applications for PRISMA recommendations from January 2013 to December 2023. Overall, 11 studies met all the inclusion criteria. The functionality of mHealth apps included inform, instruct, record, display, guide, remind/alert, and communicate. Most of the apps have multifunctionality. The usability was categorized into three aspects: efficiency (self-efficacy and usability), satisfaction, and effectiveness (underwent kidney transplantation and switched to hemodialysis, rehospitalization, peritonitis rate, infection rates at exit sites, mortality, fluid overload, inadequate solute clearance, biochemical values, quality of life, consumer quality index, and technology readiness). Generally, outcomes in the intervention group had better effects compared to those in the control group. Multifunctional mHealth apps show a good potential in improving the efficiency, satisfaction, and effectiveness for patients compared to traditional care. Future research should include more studies and participants to explore and verify the long-term effectiveness of mHealth apps.

Endometrial expression of antimicrobial peptides as markers of subclinical endometritis in mares.

Endometritis is a major cause of subfertility in mares. Multiparous old mares are more susceptible to developing endometritis given that ageing is associated with an altered immune response and with inadequate physiological uterine clearance after breeding, which can lead to degenerative changes in the endometrium. Molecules such as antimicrobial peptides (AMPs) have been proposed as endometritis markers in the equine species. Cross-sectional. To investigate the endometrial expression of defensin-beta 4B (DEFB4B), lysozyme (LYZ) and secretory leukocyte peptidase inhibitor (SLPI) genes in mares either affected or not by subclinical endometritis, due to the role of these AMPs in the immune response to bacteria and inflammatory reactions. Endometrial biopsy for histopathological and gene expression examinations was performed on 26 mares. The inclusion criteria for the normal mare group (NM, N = 7) were 2-4 years of age, maiden status, no clinical signs of endometritis and a uterine biopsy score of I, while for mares affected by subclinical endometritis (EM, N = 19) the inclusion criteria were 10-22 years of age, barren status for 1-3 years, no clinical signs of endometritis and a uterine biopsy score between IIA and III. A significantly higher expression of LYZ (NM: 0.76 [1.84-0.37] vs. EM: 2.78 [5.53-1.44], p = 0.0255) and DEFB4B (NM: 0.06 [0.11-0.01] vs. EM: 0.15 [0.99-0.08], p = 0.0457) genes was found in endometritis mares versus normal mares. Statistically significant moderate positive correlations were found between the level of expression of LYZ gene and both the age (r = 0.4071, p = 0.039) and the biopsy grade (r = 0.4831, p = 0.0124) of the mares. The study investigated a limited number of genes and mares, and the presence/location of the proteins coded by these genes was not confirmed within the endometrium by IHC. If the results of this study are confirmed, LYZ and DEFB4B genes can be used as markers to identify mares that are affected by subclinical endometritis.

RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis

A core pathophysiologic feature underlying many respiratory diseases is multiciliated cell dysfunction, leading to inadequate mucociliary clearance. Due to the prevalence and highly variable etiology of mucociliary dysfunction in respiratory diseases, it is critical to understand the mechanisms controlling multiciliogenesis that may be targeted to restore functional mucociliary clearance. Multicilin, in a complex with E2F4, is necessary and sufficient to drive multiciliogenesis in airway epithelia, however this does not apply to all cell types, nor does it occur evenly across all cells in the same cell population. In this study we further investigated how co-factors regulate the ability of Multicilin to drive multiciliogenesis. Combining data in mouse embryonic fibroblasts and human bronchial epithelial cells, we identify RBL2 as a repressor of the transcriptional activity of Multicilin. Knockdown of RBL2 in submerged cultures or phosphorylation of RBL2 in response to apical air exposure, in the presence of Multicilin, allows multiciliogenesis to progress. These data demonstrate a dynamic interaction between RBL2 and Multicilin that regulates the capacity of cells to differentiate and multiciliate. Identification of this mechanism has important implications for facilitating MCC differentiation in diseases with impaired mucociliary clearance.

Occurrence of COVID-19 in cystic fibrosis patients: a review.

Cystic fibrosis (CF) is a genetic ailment caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This autosomal recessive disorder is characterized by diverse pathobiological abnormalities, such as the disorder of CFTR channels in mucosal surfaces, caused by inadequate clearance of mucus and sputum, in addition to the malfunctioning of mucous organs. However, the primary motive of mortality in CF patients is pulmonary failure, which is attributed to the colonization of opportunistic microorganisms, formation of resistant biofilms, and a subsequent decline in lung characteristics. In December 2019, the World Health Organization (WHO) declared the outbreak of the radical coronavirus disease 2019 (COVID-19) as a worldwide public health crisis, which unexpectedly spread not only within China but also globally. Given that the respiration system is the primary target of the COVID-19 virus, it is crucial to investigate the impact of COVID-19 on the pathogenesis and mortality of CF patients, mainly in the context of acute respiratory distress syndrome (ARDS). Therefore, the goal of this review is to comprehensively review the present literature on the relationship between cystic fibrosis, COVID-19 contamination, and development of ARDS. Several investigations performed during the early stages of the virus outbreak have discovered unexpected findings regarding the occurrence and effectiveness of COVID-19 in individuals with CF. Contrary to initial expectancies, the rate of infection and the effectiveness of the virus in CF patients are lower than those in the overall population. This finding may be attributed to different factors, including the presence of thick mucus, social avoidance, using remedies that include azithromycin, the fairly younger age of CF patients, decreased presence of ACE-2 receptors, and the effect of CFTR channel disorder on the replication cycle and infectivity of the virus. However, it is important to notice that certain situations, which include undergoing a transplant, can also doubtlessly boost the susceptibility of CF patients to COVID-19. Furthermore, with an increase in age in CF patients, it is vital to take into account the prevalence of the SARS-CoV-2 virus in this population. Therefore, ordinary surveillance of CF patients is vital to evaluate and save the population from the capability of transmission of the virus given the various factors that contribute to the spread of the SARS-CoV-2 outbreak in this precise organization.

APPLICATION OF SIMPLE INHALATION THERAPY IN PULMONARY TB PATIENTS TO OVERCOME THE INEFECTIVENESS OF BREATH WAY CLEANING

Background: Inadequate airway clearance is one of the nursing issues that arises during the pulmonary tuberculosis disease process. If untreated, ineffective airway clearance can result in hypoxemia, decreased consciousness, and even cell death. Objective: The purpose of this study is to see that simple inhalation therapy can help pulmonary tuberculosis patients at the Banyu Urip Community Health Center to overcome ineffective airway clearance. Methods: The research methodology combines a case study approach with a family nursing process approach, with one case as the unit of analysis, Mrs. K, a pulmonary tuberculosis patient who get treatment at the Banyu Urip Community Health Center working area. Data was gathered through interviews, physical examinations, supporting examinations, and a literature review. In the study, 350 ml of hot water steam and 5 drops of eucalyptus oil were applied twice a day for three days, for 10-15 minutes. Result: The research results of simple inhalation therapy proved to have a positive effect on Mrs. K, as evidenced by a reduction in verbal complaints, including ease in driving out secretions, respiratory frequency was within normal limits, and breathing became easier, because the cineol content of eucalyptus oil has mucolytic, bronchodilator, and anti-inflammatory functions. Conclusion: To overcome airway ineffectiveness and improve health status, simple inhalation therapy combined with eucalyptus oil can be used as an alternative. Non-pharmacological techniques that are simple, easy to use but provide numerous benefits in health care facilities, such as simple inhalation therapy, are expected of health care workers.

Optimal timing of nirmatrelvir/ritonavir treatment after COVID-19 symptom onset or diagnosis: target trial emulation

Reports of symptomatic rebound and/or test re-positivity among COVID-19 patients following the standard five-day treatment course of nirmatrelvir/ritonavir have sparked debates regarding optimal treatment timing and dosage. It is unclear whether initiating nirmatrelvir/ritonavir immediately after symptom onset would improve clinical outcomes and/or lead to post-treatment viral burden rebound due to inadequate viral clearance during treatment. Here we show that, by emulating a randomized target trial using real-world electronic medical record data from all 87,070 adult users of nirmatrelvir/ritonavir in Hong Kong between 16th March 2022 and 15th January 2023, early initiation of nirmatrelvir/ritonavir treatment (0 to 1 days after symptom onset or diagnosis) significantly reduced the incidence of 28-day all-cause mortality and hospitalization compared to delayed initiation (2 or more days) (absolute risk reduction [ARR]: 1.50% (95% confidence interval 1.17-1.80%); relative risk [RR]: 0.77 (0.73, 0.82)), but may be associated with a significant elevated risk of viral burden rebound (ARR: −1.08% (−1.55%, −0.46%)), although the latter estimates were associated with high uncertainty due to limited sample sizes. As such, patients should continue to initiate nirmatrelvir/ritonavir early after symptom onset or diagnosis to better protect against the more serious outcomes of hospitalization and mortality.

Long COVID-19 Infections and Organizing Pneumonia in a Series of Patients with Indolent Lymphoma Treated with Rituximab

Background: Patients with hematologic malignancies have an increased risk of complications and mortality from COVID-19 (SARS-CoV-2). These patients are often more susceptible to protracted COVID-19 infections (e.g., long COVID-19). In addition, patients treated with the CD20-targeted immunotherapy rituximab in B-cell lymphomas are at greater risk for a protracted clinical course with COVID-19, including care in the ICU for respiratory failure. Hypogammaglobulinemia is an independent predictor of increased risk for long-COVID19. Immune depletion both leads to a persistent detection of SARS-CoV-2 and an inability to mount a sustained immune response. Other authors have reported on the appearance of a delayed organizing pneumonia (OP) after acute COVID-19 infection, but these patients were not immunocompromised by rituximab. In this case series, we report on three patients with indolent lymphoma who had the delayed presentation of long COVID-19 after an acute infection. All three were previously treated with rituximab, and each case was notable for prolonged OP that was refractory to steroid therapy. Methods: Summative data for the three patient cases was aggregated from the medical record including available physician notes, diagnostic body imaging, and laboratory data. Results: In total, we found three cases of long COVID-19 in patients with indolent lymphoma from our institution (Table 1). Patient 1 received just two doses of rituximab, Patient 2 received three doses of rituximab, and Patient 3 was treated with rituximab intermittently for nearly three years. All three patients experienced their first COVID-19 infections in August 2022 and had low IgG. This was followed by complications including acute hypoxemic respiratory failure, pulmonary embolism, and organizing pneumonia in these patients two to three months thereafter. These patients continue to have ongoing chronic hypoxemic respiratory failure requiring immune suppression and continuous oxygen support. Conclusions: Immune depletion with rituximab in patients with indolent lymphomas can put them at significant risk of long COVID-19, OP, and chronic hypoxemic respiratory failure after contracting SARS-Cov-2. Such patients may benefit from prolonged immune suppression, but the exact duration remains unclear. The mechanism of long COVID-19 and refractory OP is unclear and complex. Possible mechanisms may include inadequate clearance of virus or a dysfunctional immune response. Table 1: Lymphoma patients who received rituximab and then developed long COVID-19

Genetic association between vitamin D receptor gene and Saudi patients confirmed with Familial Hypercholesterolemia.

Familial Hypercholesterolemia (FH) is a common condition caused by inherited genetic abnormalities. Inadequate clearance of the circulating low-density lipoproteins (LDL) is the primary cause of the excessive concentrations of LDL seen in FH patients. The relation with vitamin D deficiency and vitamin D receptor (VDR) gene is well documented in the Saudi Arabia. The aim of this study was to investigate the role of molecular analysis studied between FH patients and fours polymorphisms associated with VDR gene in Saudi Population. In this case-control study, 120 patients were selected, and 50 patients were confirmed as FH and 70 subjects were confirmed as healthy controls. Genotyping was performed with polymerase chain reaction followed by restriction fragment length polymorphism analysis using ApaI, BsmI, TaqI and FokI polymorphisms in the VDR gene. The current study results confirmed no association between clinical characteristics studied between FH cases and controls (p>0.05). Hardy Weinberg Equilibrium analysis was present in ApaI and FokI polymorphisms (p<0.05). Only ApaI (C vs A: OR-15.1 (95% CI:5.78-39.41); p<0.001; AC+CC vs AA: OR-6.59 (95% CI:2.42-17.95); p=0.0006) and BsmI (G vs A: OR-2.88 (95% CI:1.54-5.38); p=0.0006 and AG+GG vs AA: OR-3.79 (95% CI:1.72-8.35); p=0.0007) polymorphisms showed both allele and genotype association between FH patients and controls. ANOVA analysis confirmed that TG levels were associated (p=0.02) with combination of heterozygous and homozygous genotypes present in all four polymorphisms studied in this population. ApaI and BsmI polymorphisms in the VDR gene showed association with FH patients in the Saudi Population.

The Use of Caplacizumab in COVID-19-Related TTP

Introduction Thrombotic Thrombocytopenic Purpura (TTP) is a rare but feared hematological disorder encountered in the inpatient setting. COVID-19-associated TTP is a lesser understood phenomenon, with slightly different symptomology and clinical course. Prompt identification is essential since TTP is a medical emergency which carries a 90% risk of mortality if untreated. Several aspects of treatment, including the use of agents like caplacizumab as monotherapy and therapy duration, are poorly defined in the literature. In this case report, we discuss one such case of post-COVID TTP and explore the therapeutic challenges that clinicians should be aware of when using caplacizumab. Case A 49-year-old female presented with brief changes in mentation and confusion, as well as an associated headache, sore throat, myalgias, and fever for 10 days. The patient tested positive for the COVID-19 antigen 3 days prior to presentation. The patient was hemodynamically stable on arrival, although tachycardic to 94 beats per minute. Initial labs revealed acute normocytic anemia (Hb 7.4 g/dl from a baseline of 12.1 g/dl) and acute, severe thrombocytopenia (9 K/ul from a baseline of 217 K/ul) with schistocytes present on peripheral blood smear. Elevated lactate dehydrogenase (LDH) and low haptoglobin suggested hemolysis. PT, INR, PTT, d-dimer, fibrinogen, and fibrin degradation product (FDP) did not suggest disseminated intravascular coagulation (DIC). TTP was highly suspected with a PLASMIC score of 7. Therapeutic plasma exchange (TPE) was started emergently on day of admission. Additional treatments that were administered include methylprednisolone (1g daily for 3 days), rituximab (375mg/m2), and caplacizumab (11mg before and after TPE on Day 1, then 11 mg daily thereafter). Caplacizumab was administered daily through Day 4, then stopped because our hospital pharmacy could not procure the drug. Nevertheless, by day 4, platelets had improved to &amp;gt;150 K/ul and LDH to &amp;lt;200 IU/l for 2 consecutive days. From Day 4 to Day 10, TPE was given every other day. However, on day 10 the platelets decreased to 11 K/ul. Both daily TPE and caplacizumab was re-initiated. ADAMTS 13 level was &amp;lt;2% at admission and Day 9, later increased to 54.1% on Day 15. ADAMTS 13 antibody levels were &amp;gt;164 U/ml on the day of admission, 67 U/ml on Day 9, and undetectable on Day 15. The patient was discharged on Day 22 and completed a 30-day course of caplacizumab. Follow-up showed sustained remission at 2.5 months with ADAMSTS13 level of 90.8%, platelet count 130 K/ul and the LDH level of 136 U/l. Discussion Caplacizumab is a bivalent anti-VWF immunoglobulin approved in 2019 for treating acquired TTP in conjunction with TPE and other immunosuppressive therapies. The TITAN trial showed significantly lower 30-day exacerbations in the caplacizumab group compared to the placebo group, but a higher rate of relapse in the caplacizumab group in the following month. Patients in the caplacizumab group received fewer TPE sessions overall. Paradoxically HERCULES trial showed 67% lower recurrence in the caplacizumab group. These results in the HERCULES trial were attributed to caplacizumab treatment lengths that could be expanded based on ADAMTS13 activity &amp;lt;10%. In our case, given the high bleeding risk and lack of cost-effectiveness while inpatient, caplacizumab was discontinued and TPE decreased to alternate day dosing following adequate clinical response. It is difficult to predict whether premature discontinuation of caplacizumab or early weaning of TPE triggered recurrence, since both therapies were discontinued on Day 5. This case demonstrates a clinical conundrum of whether caplacizumab can lead to early discontinuation of TPE with inadequate clearance of ADAMTS13 antibody, leading to early relapses. A review of current literature and our experience suggest that Caplacizumab may be very effective in improving platelet count and reducing relapse rates, especially when decisions to discontinue the drug are based on ADAMTS-13 levels. However, lack of cost-effectiveness is a limiting factor, and high bleeding risks must be considered before deciding to start caplacizumab in patients with refractory or severe TTP.

Laparoscopic common bile duct exploration: what factors determine success?

Laparoscopic common bile duct exploration (LCBDE) has been shown to be effective in managing choledocholithiasis whilst avoiding ERCP-related complications. However, patient and technical factors effects outcome. This study aimed to explore the matters effecting the failure of LCBDE. All patients who underwent a laparoscopic cholecystectomy (LC) between 2007 and 2021 were identified using a prospective database. Data were collected for patients who underwent LCBDE including demographics, pre-operative investigations, intra-operative findings, technique of bile duct clearance and clearance rates, and post-operative outcomes. Predictors of failed LCBDE were identified. Laparoscopic cholecystectomy was performed in 3648 patients. Of these, 374 underwent LCBDE for suspected choledocholithiasis. Choledochoscopy was most frequently used (58.8%) with a success rate of 84.1%. Small cystic duct diameter (4.7 vs. 3.4 mm, P = 0.002), stone size >6 mm (P = 0.02), stone: cystic duct ratio >1 (P = 0.04), and >3 stones was associated with failed LCBDE by univariate analysis. Small cystic duct diameter (OR: 0.45, 95% CI: 0.26-0.77, P = 0.004) and stone size >6 mm (OR: 0.23, 95% CI: 0.06-0.92), P = 0.04) correlated with failure by multivariate analysis. Failed LCBDE was associated with increased length of stay (6.6 days vs. 3.1 days, P = 0.001), however the rate of serious complications or mortality was unaffected. LCBDE is safe and effective in managing choledocholithiasis. Factors such as cystic duct diameter, size and number of CBD stones, and stone: cystic duct ratio are associated with increased likelihood of inadequate clearance. The presence of these factors can help clinicians in decision making during LCBDE to improve chance of success.

Failure Investigation of Blank Holder Force (BHF) Control in The Outside Bracket For Front Seat

This study investigated the failure of the Blank Holder Force (BHF) control in the outside bracket for the front seat. The production process involved progressive dies consisting of nine stations: first pierce, first trim, second trim, idle, flange, idle, second pierce, idle, and parting. However, at the 7th-9th station, the pilot hole in the product deforms into an oval shape, which is undesirable. Gemba-Kaizen methods were used in this study, and primary data were collected by comparing the design and actual progressive dies. The results showed that product defects are primarily caused by an unbalanced BHF and inadequate piercing clearance. A uniform distribution of force during the forming process is obtained by reducing the spring number on the blank holder. This reduces the force generated during the process. Furthermore, the die clearance was increased from 0.01 mm to 0.1 mm, making press and die alignment less critical and requiring less cutting and stripping forces

Effects of COVID-19 and vaccination on the human immune system: cases of lymphopenia and autoimmunity

Effects of COVID-19 and vaccination on the human immune system: cases of lymphopenia and autoimmunity