Side Effects Of Therapy Research Articles

Encapsulation of Dexamethasone into mRNA–Lipid Nanoparticles Is a Promising Approach for the Development of Liver-Targeted Anti-Inflammatory Therapies

The objective of this study was to develop two lipid nanoparticle (LNP) formulations capable of efficiently expressing a reporter mRNA while co-delivering the anti-inflammatory drug dexamethasone (DX) to reduce inflammatory side effects in protein replacement therapies. Two types of LNPs were developed, in which 25% of cholesterol was replaced by DX. These LNPs contained either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as a helper lipid. The resulting LNPs exhibited high stability, homogeneity, and near-neutral Zeta potentials. SAXS experiments confirmed DX incorporation into the LNP core, with slow in vitro DX release observed over 48 h. The LNPs achieved high mRNA encapsulation efficiency (95–100%) and effectively transfected HepG2 cells, dendritic cells, and hPBMCs. While LNPs increased cytokine release (IL-1β, TNF-α, MCP-1), LNPs-DX significantly reduced cytokine levels, demonstrating enhanced anti-inflammatory properties while maintaining mRNA expression levels. In vivo biodistribution showed predominant liver localization post-intramuscular injection, regardless of the DSPC or DOPE composition. LNPs co-loaded with mRNA and DX are promising candidates for continuous protein replacement. Due to their ability to reduce treatment-related inflammation while maintaining significant mRNA expression levels, these LNPs are perfectly suited for the treatment of liver-related metabolic diseases.

Transthyretin Cardiac Amyloidosis: Insights into Wild-Type Variants and Familial Amyloid Cardiomyopathy

Transthyretin (TTR) cardiac amyloidosis is a progressive condition characterized by amyloid fibril deposition in the heart, leading to heart failure. This review focuses on insights into wild-type (ATTRwt) and familial (ATTRm) variants of TTR amyloidosis. The pathophysiology involves TTR tetramer destabilization, monomer misfolding, and amyloid fibril formation. Therapeutic advances, including TTR stabilizers like tafamidis and Diflunisal, and gene-silencing agents such as patisiran and inotersen, show promise in managing the disease. Despite these advancements, early diagnosis remains challenging, and side effects of current therapies necessitate the development of safer, more effective treatments. Future research should focus on novel therapies, improved diagnostic methods, and personalized treatment strategies to enhance patient outcomes. This review underscores the importance of continued innovation and collaboration in tackling TTR cardiac amyloidosis.

The association between religiosity, suicidality, psychological distress, and quality of life among breast cancer patients, an example of a Middle Eastern population.

The study aimed to explore the relationship between religiosity, psychological distress, and quality of life (QOL) in Saudi breast cancer patients. Utilizing a multi-center cross-sectional design, 277 patients were recruited. Patients completed questionnaires assessing religiosity, depression, anxiety, suicidality, and QOL. Results revealed a high prevalence of depression (35.7%) and anxiety (18.1%), with no significant variations in internal religiosity across different health stages, despite high levels of perceived social support. Suicidal ideation was reported by a small proportion of patients (2.5%). Multivariate analysis identified anxiety, therapy side effects, and breast symptoms as significant predictors of depression, while depression and previous psychiatric treatment predicted anxiety levels. QOL assessments indicated that body image received the highest satisfaction ratings, while sexual function received the lowest. These findings highlight the critical need for integrated mental health support in the treatment regimen of breast cancer patients.

6609 Central Serous Chorioretinopathy in the Eyes of the Beholder of Testosterone Depot Injection

Abstract Disclosure: H. Ni: None. D. Kankanamge: None. J. Jabbour: None. V.A. Preda: None. Background: Central serous chorioretinopathy (CSC) is a characterised by subretinal fluid accumulation causing detachment of the neurosensory retina and visual disturbance[1]. It has been postulated that increased focal choriocapillaris permeability results in leakage of interstial fluid into the subretinal space[1]. CSC is a rare side effect of testosterone therapy, the exact mechanism is unclear. Case : We present a 32-year-old male gym manager who has been self-administering anabolic steroids with testsoterone ethanoate IM injections every 14 days for body building. He reported left blurred vision for 8 weeks. He was normotensive and reported taking doxycycline and azithromycin for mycoplasma genitalia. There was no history of glucocorticoid exposure, smoking, alcohol use, gastoesophageal reflux disease, hypertension, shift work, sleep apnoea, nor other established risk factors for CSC. The visual acuity was OD 6/6 and OS 6/9 with intraocular pressures of 12mmHg on the right and 15mmg on the left. Fundoscopy revealed a left serous macular elevation involving the left fovea. A macular OCT confirmed the left acute central serous chorioretinopathy and right retinal pigment epithelial changes. The latter were suggestive of right CSC in the past. Discussion: Androgens have been associated with CSC in the literature. It has been hypothesised that exogenous testosterone may cause increased choriodal blood flow and permeability, promote atheroscleorsis, cause sodium retention and potentially interact with retinal pigment epithelium (RPE) via androgen receptors4. Intramuscular testosterone therapy causes fluctuation in plasma testosterone concentration (which is thought to be more relevant than absolute value of testosterone). Most cases (60%) of CSC resolve spontaneously, and appear to coincide with cessation of testosterone therapy5. Conclusion: Clinicans need to be alert to the use of testosterone and other anabolic steroids, prescribed or self administered, particularly in their patients with CSC or who have other risk factors for CSC, such as corticosteroids, smoking and hypertension.

7533 Mifepristone For Primary Hypercortisolism Contributing To Profound Hypokalemia

Abstract Disclosure: J. Watkins: None. J.G. Melendez-Rivera: None. E. Florin: None. K.B. Rivera: None. Background: Primary hypercortisolism is typically treated surgically, but when adrenalectomy is not pursued, medical therapy can be effective. Adrenal enzyme inhibitors or glucocorticoid antagonists can be used. Mifepristone is the only available glucocorticoid antagonist at this time. Mifepristone is approved specifically for glucose control in Cushing’s syndrome. Because mifepristone blocks cortisol action rather than production, hormone levels may increase and are unhelpful in titrating the mifepristone dose. Rather, titration is based on clinical manifestations of Cushing’s syndrome. Further, the increased hormone levels can lead to increased activation of mineralocorticoid receptor, in addition to the increased activation caused by hypercortisolism, which can cause hypokalemia. Clinical Case: An 82-year-old woman had been following with endocrinology for hypercortisolism found to be secondary to bilateral adrenal adenomas. She preferred medical therapy rather than surgery given her age, and she was started on mifepristone 300 mg/day. Within a few weeks, she developed leg swelling and was started on a low dose of chlorthalidone by her primary care doctor. She then presented to the emergency department after five days of nausea, abdominal pain, palpitations, and reduced oral intake. She was found to have severe hypokalemia (potassium 1.8 mEq/L, normal 3.5 - 5.0 mEq/L), and her creatinine was 0.97 µmol/L (baseline 0.6-0.75 µmol/L). Physical exam was unremarkable. CT abdomen/pelvis revealed three adrenal lesions, similar to a study from one year prior. Her mifepristone was stopped, and she was given potassium supplementation and started on spironolactone with eventual stabilization of her potassium level. She was also started on ketoconazole for management of her hypercortisolism. It was discussed that she might now consider adrenal vein sampling to pursue adrenalectomy. Severe hypokalemia and borderline metabolic alkalosis were most likely multifactorial in etiology. Hypercortisolism predisposed the patient to hypokalemia. She was then started on mifepristone, which inhibits the glucocorticoid receptor thereby increasing activation of the mineralocorticoid receptor, which likely further contributed to hypokalemia. The leg swelling that she developed and saw her primary doctor for may have been a sign of over-activation of the mineralocorticoid receptor due to the mifepristone, and prescription of chlorthalidone at that time would have worsened the hypokalemia that was likely present at that time. Conclusion: It is important to be aware of the possible severity of side effects of medical therapy for hypercortisolism, such as severe hypokalemia. There is a role for increased awareness of routine monitoring of potassium levels, as well as considering spironolactone in many patients even prior to onset of hypokalemia. Presentation: 6/3/2024

7172 Osteoporosis Associated with Antiretroviral Therapy - Case report

Abstract Disclosure: C.E. Guillen Lopez: None. L.A. Sanchez Ato: None. A. Patel: None. A. Molkina: None. T. Ayub: None. L. Robles: None. A. Arce Gastelum: None. Osteoporosis presents a substantial public health challenge, contributing significantly to morbidity and mortality through fractures. While postmenopausal osteoporosis is common, secondary osteoporosis affects a significant number of patients, including over 30% of postmenopausal and 50-80% of men. People living with HIV (PLWH) experience age-related medical comorbidities earlier and more extensively than those without HIV. The compromised bone health in PLWH is attributed to factors associated with the virus, antiretroviral therapy (ART) side effects, and health disparities such as inadequate nutrition, low body weight, hypogonadism, vitamin D deficiency, and increased recreational substance use. More recently, it has become apparent that vertebral fractures are more common in PLWH, with a prevalence of 11.1% and a 2.30-fold more significant risk than the general population. Low bone mass density (BMD) is twice as common in PLWH, increasing to 3 times as common in PLWH on ART. ART initiation leads to transient bone loss with nucleotide reverse transcriptase inhibitors such as tenofovir disoproxil fumarate (TDF) and protease inhibitors, causing higher BMD loss. In contrast, integrase and specific reverse-transcriptase inhibitors have minimal adverse effects on BMD. The newer formulation, tenofovir alafenamide (TAF), is believed to have a more favorable impact on bone health than TDF. The repercussions of diminished bone health, particularly osteoporotic fractures, have significant medical and economic implications. They are leading to early mortality, disability, and a loss of independence. The HIV Medicine Association (HIVMA) and Infectious Diseases Society of America (IDSA) recommend BMD screening for all HIV-infected patients at 50 years. 58-year-old male PLWH reveals a history of osteoporosis with multiple spinal (L1, L4-5, S1) and bilateral wrist fractures on TDF for 15 years. The patient has been treated with bisphosphonates. Alendronate was initially prescribed, but due to acid reflux side effects, zoledronic acid was a better option. Despite various ART regimens, Dolutegravir/Lamivudine was started four years ago without further fractures. Recent bone density assessments showed improvement in the lumbar spine, returning to a normal range with a T-score of 0.6. However, the left femoral neck remains at -2.5, and the right femoral neck is at -2.2, showing minimal change. To enhance BMD in PLWH on ART, transitioning to alternatives with lower bone loss associations and using bisphosphonates as tolerated are suggested. As the HIV-infected population ages, proactive screening for low BMD is vital to manage evolving health needs and prevent bone-related complications. A holistic approach includes evaluation for secondary etiologies of osteoporosis, medical treatment, and vitamin D and calcium supplementation. Presentation: 6/3/2024

Sex differences in clinical presentation, treatment response, and side effects of nutritional therapy among patients at nutritional risk - a secondary analysis of the randomized clinical trial effort

Sex differences in clinical presentation, treatment response, and side effects of nutritional therapy among patients at nutritional risk - a secondary analysis of the randomized clinical trial effort

Measuring what really matters: Advocacy-led co-creation and accrual of a pan-cancer QoL survey.

240 Background: Implementing co-creation methods in research may provide vital input to improve accrual, retention, and research value. Advocates for Collaborative Education (ACE), a global coalition of patient, community, research, and policy advocates, used co-creation methodology with patients, survivors, and metavivors to Design, Develop , and Deploy a survey to define and quantify QoL impacts across a large sample of individuals with a diagnosis or history of cancer. Methods: With a defined primary objective to “gain insight into challenges faced by individuals with a history or diagnosis of cancer and how these challenges impact their life and quality of life,” a co-creation team of individuals with lived experience in early stage or metastatic cancers was established. In the Design phase, co-creation team members were interviewed and engaged in discussions on side effect measurement and impact. They were asked a variety of questions, including what side effects they believed were most impactful to QoL, what elements they felt were missing in conversations around QoL, and how accurately they felt QoL was measured in the clinical setting. In the Develop phase, survey questions were developed and vetted with the co-creation team. In the Deploy phase, co-creation team members, advocate members of the ACE community, and aligned advocacy groups, were key to recruiting a broad audience via electronic distribution and social media platforms. Results: Efforts resulted in the co-creation of a six-section, 93 question, IRB-exempt survey. The co-creation team identified 17 treatment-related side effects that were incorporated into the survey. Survey questions asked respondents about perceived severity of side effects, how well informed they felt about possibilities of experiencing these side effects, access to supportive care, side effects of supportive care therapies, and personal preferences for receiving cancer-related information. A unique measurement scale was shaped by the co-creation team to be more reflective of side effect impact on QoL. In five weeks, the survey accrued over 500 responses across a variety of cancer types (15+), stages (0 - IV), ages, statuses, and racial groups. Conclusions: Co-creation methods were used in Design to identify side effect experiences in cancer treatment and validate what matters most to individuals with cancer; in Develop to validate a pan-cancer survey examining what mattered to the audience of interest; and in Deploy to rapidly accrue a large and diverse set of responses through advocacy partnerships. Co-creation also identified layers of side effect management challenges that cannot be reflected in current rubrics for QoL measurement. While co-creation may seem daunting, this study provides a template for effective, quality partnerships between study teams, advocates, and advocacy groups for implementing co-creation methods in the cancer setting.

A rare side effect of antithyroid drug therapy

We report a case of Graves' disease in a patient who initially received carbimazole therapy, which was switched to propylthiouracil due to adverse effects. After 14 months of propylthiouracil therapy, the patient developed cutaneous ANCA-associated vasculitis. Prompt cessation of propylthiouracil and topical treatment led to complete resolution of the skin lesions.

Predictive modeling of sensory responses in deep brain stimulation.

Although stimulation-induced sensations are typically considered undesirable side effects in clinical DBS therapy, there are emerging scenarios, such as computer-brain interface applications, where these sensations may be intentionally created. The selection of stimulation parameters, whether to avoid or induce sensations, is a challenging task due to the vast parameter space involved. This study aims to streamline DBS parameter selection by employing a machine learning model to predict the occurrence and somatic location of paresthesias in response to thalamic DBS. We used a dataset comprising 3,359 paresthetic sensations collected from 18 thalamic DBS leads from 10 individuals in two clinical centers. For each stimulation, we modeled the Volume of Tissue Activation (VTA). We then used the stimulation parameters and the VTA information to train a machine learning model to predict the occurrence of sensations and their corresponding somatic areas. Our results show fair to substantial agreement with ground truth in predicting the presence and somatic location of DBS-evoked paresthesias, with Kappa values ranging from 0.31 to 0.72. We observed comparable performance in predicting the presence of paresthesias for both seen and unseen cases (Kappa 0.72 vs. 0.60). However, Kappa agreement for predicting specific somatic locations was significantly lower for unseen cases (0.53 vs. 0.31). The results suggest that machine learning can potentially be used to optimize DBS parameter selection, leading to faster and more efficient postoperative management. Outcome predictions may be used to guide clinical DBS programming or tuning of DBS based computer-brain interfaces.

Development and characterization of formulations based on combinatorial potential of antivirals against genital herpes.

Herpes simplex virus type 2 (HSV-2) treatment faces challenges due to antiviral resistance and systemic side effects of oral therapies. Local delivery of antiviral agents, such as tenofovir (TDF) and zinc acetate dihydrate (ZAD), may offer improved efficacy and reduced systemic toxicity. This study's objective is to develop and evaluate local unit dose formulations of TDF and ZAD combination for local treatment of HSV-2 infection and exploring their individual and combinatory effects in vitro. The study involved the development of immediate-release film and pessary formulations containing TDF and ZAD. These formulations were characterized for physicochemical properties and in vitro drug release profiles. Cytotoxicity and antiviral activity assays were conducted to evaluate the individual and combinatory effects of TDF and ZAD. Film formulations released over 90% of the drugs within 1h, and pessary formulations within 90min, ensuring effective local drug delivery. ZAD showed moderate antiviral activity while TDF exhibited significant antiviral activity at non-cytotoxic concentrations. The combination of TDF and ZAD demonstrated synergistic effects in co-infection treatments, reducing the concentration required for 50% inhibition of HSV-2. Developed film and pessary formulations offer consistent and predictable local drug delivery, enhancing antiviral efficacy while minimizing systemic side effects. The combination of TDF and ZAD showed potential synergy against HSV-2, particularly in co-infection treatments. Further preclinical studies on pharmacokinetics, safety, and efficacy are necessary to advance these formulations toward clinical application.

Клиническое обоснование значимости оценки уровня эстрадиола у мужчин с синдромом гипогонадизма на фоне терапии по стабилизации уровня тестостерона.

Introduction. A significant reason for the decrease in the effectiveness of testosterone replacement therapy (TRT) in men is the increased activity of the aromatase enzyme in overweight and obese patients, when under its influence estrogens are converted from androgens (the transition of testosterone to estradiol) mainly in adipose tissue, leading to an increase in estradiol levels. That is, with exogenous administration of testosterone, estradiol becomes overabundant, thereby the positive effects of TRT are weakened and even often leveled, dangerous side effects of hyperestradiolemia appear, that is, without careful monitoring and normalization of estradiol levels, the effectiveness of TRT turns out to be low, and the side effect of therapy, due to high estrogens, on the body is high. The aim of research was to increase the effectiveness of testosterone replacement therapy for hypogonadism in obese patients. Material and methods. A two-center prospective study was conducted to study TRT for hypogonadism. The results of examination and treatment of 106 men aged 35-59 years (average age 45.9±7.2 years) with hypogonadism syndrome, who were prescribed TRT Omnadren 250 mg 1 ml/m, were analyzed. The levels of total testosterone, estradiol, and prolactin were monitored 48 hours after injection (Omnadren pharmacokinetics: Cmax of testosterone in blood plasma occurs within 24-48 hours), as well as level of hormones on day 10 with Aging Male Screening (AMS) control. Results. In patients with TRT, on the second day after 48 hours, as well as after 10 days inclusive, an increase in testosterone and estradiol was statistically significant (p<0.01), but in overweight and obese individuals, the aromatization of testosterone into estradiol was significantly higher than in patients with normal body mass index (BMI), with at the same time, according to the scores of the AMS questionnaire, there was an improvement clinically, however, in patients with obesity it was clinically less significant due to significantly increased level of estradiol at the time of treatment. Conclusions. It was found that patients with increased BMI have worse treatment results with elevated estradiol, which requires monitoring of estradiol starting from 2-3 days and later on day 10 in order to titrate the frequency of injections of testosterone preparations and correct the level of estradiol to physiological ones.

Results of the Italian cross-sectional web-based survey "Nutrition and breast cancer, what would you like to know?" An attempt to collect and respond to patients' information needs, through social media.

Several studies have demonstrated that, following a breast cancer (BC) diagnosis, patients are eager to obtain information on cancer and nutrition, in order to ameliorate both their quality of life (QoL) and disease outcome. To avoid BC survivors to get wrong information from unreliable sources, healthcare providers need to be aware of patients' needs, to guide them toward optimal nutrition recommendations, aimed at preventing tumor recurrence and increasing survival rates. The cross-sectional web-based survey "Nutrition and breast cancer, what would you like to know?" has been conceived and conducted, in Italy, between the 2nd and the 25th of June 2023. The link to the 19-items questionnaire, structured in 6 sections, was distributed via social media (Facebook and Instagram), newsletter, institutional websites, and printed flyers. Patients' responses were collected and analyzed, reporting absolute and relative frequencies. A total of 1616 participants (98.9% female and 1.1% male), with an average age of 47.5 years, answered the survey. Only subjects who declared having previously received a BC diagnosis (N=1159, 71.7%) were included in the present analysis. Overall, the respondents showed a wide interest in understanding whether nutrition might help to manage therapy side effects, as well as knowing how specific diets, foods, nutrients, and supplements could affect disease onset, progression and prognosis. Importantly, the need to receive evidence-based information from the "referring physician/specialist" and "nutritionist/dietitian" was expressed by 95.8% and 88.8% of them, respectively. In this study, we primarily aimed at intercepting nutrition information needs and sources of an Italian BC survivors' group. Based on that, we first organized a proactive digital intervention, to respond via Instagram live broadcasts to patients' "cancer and nutrition"-related questions. Secondly, we arranged a healthcare providers dedicated-workshop focused on the latest evidence-based knowledge on nutrition and BC. It is crucial, in fact, that once healthcare professionals capture patients' information needs, they can respond with appropriate nutritional guidance, counseling and education programs, while counteracting misleading and incorrect messages.

Sex differences in clinical presentation, treatment response, and side effects of nutritional therapy among patients at nutritional risk: a secondary analysis of the randomized clinical trial EFFORT

BackgroundConsidering sex-specific factors has become an increasingly recognized area for research and practice, in the field of clinical nutrition, there is insufficient evidence regarding differences in clinical presentation, treatment response, and side effects of nutritional therapy among female and male patients. ObjectivesWe hypothesized that the clinical presentation, response to nutritional therapy, and side effects from the intervention would differ in the two sexes. MethodsThis secondary analysis investigated differences among female and male patients at risk for malnutrition regarding initial presentation, clinical outcomes, and treatment response in patients included in the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled trial comparing individualized nutritional support to usual care. ResultsOf 2028 patients included in the trial, 964 were females and 1064 were males. The nutritional history and clinical presentation of female patients was different: they consumed less food and had a greater loss of appetite than the male population. Male patients had higher risk for mortality at 180 d [27% compared with 19%; adjusted hazards ratio (HR): 1.35; 95% CI: 1.12, 1.63] and further adverse clinical outcomes. However, there was no difference in the effect of nutritional support on mortality among female and male patients (HR: 0.76; 95% CI: 0.45, 1.27, compared with HR: 0.81; 95% CI: 0.54, 1.21, respectively; P-interaction = 0.939). ConclusionsResults of this multicenter randomized trial suggest that multimorbid female inpatients have a different clinical presentation and are more prone to loss of appetite and reduced daily dietary intake than male inpatients. Importantly, the favorable response to nutritional interventions was similar in both sexes.This trial was registered at clinicaltrials.gov as NCT02517476.

Steroid myopathy in patients with myasthenia gravis: a literature review

Steroid myopathy is a common drug-induced non-inflammatory myopathy that affects patients requiring long-term glucocorticoid treatment for various autoimmune, inflammatory and oncological diseases. According to the neurology clinical practice guidelines, non-fluorinated glucocorticoids are the first-line pathogen-directed therapy for a number of dysimmune neuromuscular disorders, including myasthenia gravis. Long-term high-dose steroid treatment regime for myasthenia gravis leads to both acute and chronic development of glucocorticoids-induced proximal muscle weakness and atrophy. Steroid myopathy, along with other undesirable side effects of glucocorticoids therapy, impact health-related quality of life, patient satisfaction and adherence to treatment. Hence, further studies are required to expand our knowledge of clinical evaluation, diagnostic testing and prevention approaches for glucocorticoids-induced myopathy. The aim of this literature review is to analyze existing data on pathogenesis, diagnostic tools and treatment strategies for steroid myopathy.

Comparison of combination therapy with tamsulosin and dutasteride or finasteride in patients with benign prostatic hyperplasia: a randomized clinical trial

BackgroundBased on our observations at the largest outpatient urology clinic in Iran, patients for whom finasteride is prescribed as a secondary drug to tamsulosin tend to experience earlier and more severe sexual side effects without any difference in the amelioration of symptoms. This study aimed to compare the time lag, efficacy, and side effects of combination therapy with varying doses of dutasteride or finasteride added to tamsulosin for benign prostatic hyperplasia (BPH) treatment.MethodsIn this study 165 were randomized into 5 groups (each N = 33); receiving tamsulosin 0.4mg plus either of A: finasteride 3mg, B: placebo, C: dutasteride 0.25mg, D: finasteride 5mg or E: dutasteride 0.5mg. During the 6-month period of the study, International Prostate Symptom Score (IPSS), post-void residual urine (PVR), International Index of Erectile Function (IIEF-5), prostate volume (PV), prostate specific antigen (PSA) and maximum urinary flow rate (Qmax) were evaluated at baseline and at the 1st, 3rd and 6th month. The differences between each time point and baseline were then compared between groups.ResultsAt 3-month follow-up, group E exhibited a higher decrease in PSA but a greater increase in Qmax compared to group A (p = 0.047 and 0.006, respectively). Group C showed higher Qmax increase compared to group A at 3 and 6 months (p = 0.003 and 0.014) and concurrently a more pronounced PV decrease at 1 and 3 months (p = 0.047 and 0.003, respectively). Group D had a significantly more decrease in their IIEF-5 compared to group A at one-month visit (p = 0.006).ConclusionsIn summary, at the sixth-month follow-up, dutasteride demonstrated superiority over finasteride solely in enhancing Qmax. Therefore, dutasteride may be marginally more beneficial as a secondary component of combination therapy in BPH.Trial registration IRCT, IRCT20120516009772N2. Registered 18 January 2021 Retrospectively registered, https://irct.behdasht.gov.ir/search/result?query=IRCT20120516009772N2.

Conjunctival Melanoma: A Clinical Review and Update.

Conjunctival melanoma (Co-M) is an aggressive, invasive eye and eyelid cancer. Its global incidence of ~1 in a million is increasing at a rate ratio of ~1.4, but this rises sharply in over 65-year-olds. Although rare, Co-M has a devastating impact on the lives of those who develop it. Co-M is often misdiagnosed or overlooked, leading to vision loss either from the destructive effects of the tumour or side effects of therapy, facial disfigurement from radical surgery, and death from metastases. Due to its rarity, there is limited evidence for diagnosis and management; hence, there is no standardised treatment and not all cases are referred to a specialised ocular oncology centre. Recent progress in cancer immunology and genetics have revolutionised the treatment of cutaneous melanomas, which share some similarities to Co-M. Importantly, a better understanding of Co-M and its precursor lesions is urgently needed to lead to the development of novel targeted and immunotherapies both for local tumour control and disseminated disease. This review aims to provide a comprehensive clinical overview of the current knowledge regarding Co-M, its epidemiology, pathogenesis, presentation, diagnosis and recent changes in the classification of its precursor lesions, management, and recent advances in novel biological therapies for personalised treatment of this disease.

A systematic review of health-related quality of life outcomes in patients with advanced breast cancer treated with palbociclib.

Aim: To evaluate the impact of palbociclib treatment on health-related quality of life (HRQoL) in patients with hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer (HR+/HER2- aBC) or metastatic breast cancer (mBC) in both the clinical and real-world setting. Materials & methods: A systematic literature review was conducted to identify clinical trials and real-world evidence studies up to June 2023 that reported HRQoL outcomes in patients with HR+/HER2- aBC or mBC treated with Palbociclib. Results: 15 unique studies reported across 35 records were identified. Of these, seven were randomized controlled trials (RCTs), three were single-arm clinical trials and five were real-world evidence (RWE) studies. HRQoL was generally found to be maintained in patients with HR+/HER2- aBC or mBC across RCTs, single-arm clinical trials and RWE studies. HRQoL measures across instruments, study types and line of therapy, were largely reported to be at least maintained if not improved from baseline among patients treated with palbociclib and were observed to be comparable or better in the palbociclib group versus monotherapy control arm in RCTs. Similar results were seen for treatment-related outcomes (e.g., sexual functioning, upset by hair loss, systemic therapy side effects etc.), and important individual patient outcomes, including pain, fatigue and physical functioning. Findings were also consistent across key clinical characteristics (visceral metastases, neutropenia), as well as patient populations often underrepresented in clinical trials (Asian patients, older adults). Conclusion: Overall, current evidence suggests that HRQoL is largely preserved with the addition of palbociclib to endocrine therapy in patients with HR+/HER2- aBC or mBC across study types and populations.

Recurrence-Free Survival after Postoperative Hormone Therapy for Catamenial Pneumothorax.

Catamenial pneumothorax (CP) is a rare form of spontaneous pneumothorax that is linked to endometriosis; thus, it predominantly manifests in women of reproductive age. Considerable research has explored the potential benefits of postoperative hormone therapy following various surgical interventions. This study was performed to examine the clinical implications of postoperative hormone treatment in patients with CP. The study included patients who underwent surgical intervention for CP between November 2009 and February 2023. These procedures included wedge resection, diaphragm resection, and total pleural coverage. Recurrence-free survival was analyzed using the Kaplan-Meier log-rank test to assess the impact of hormone therapy. Additionally, Cox proportional hazards analysis was employed to identify risk factors associated with postoperative CP recurrence. The study included 41 patients, with a median age of 38.4 years. Among them, 27 individuals received hormone therapy, 8 of whom experienced recurrence during a median follow-up period of 1 year. Patients who received hormone therapy exhibited a lower rate of recurrence than those who did not; however, the difference was not statistically significant, likely due to the small sample size. Side effects of hormone therapy included depression (6.8%), excessive sweating (3.4%), and headache (3.4%). In the analysis of risk factors for postoperative recurrence, diaphragm resection emerged as a protective factor (hazard ratio, 0.16; 95% confidence interval, 0.03-0.77; p=0.022). Hormone treatment combined with surgery did not significantly impact recurrence in patients with CP. The application of diaphragm resection was the sole factor that displayed significance in preventing CP recurrence.

Neural networks in oncourology

In recent decades, neural networks have been widely applied in many fields of science and medicine. Accurate and early diagnosis of malignancies is a key challenge in oncology. Neural networks can analyse a wide range of medical data and identify relationships between qualitative and quantitative features. This allows for more precise and timely diagnoses. Moreover, they can be used to predict tumour progression, evaluate treatment effectiveness, and optimise treatment plans for each patientIn oncourology, the use of neural networks offers new perspectives for the diagnosis, prognosis, and treatment of various cancer conditions related to the urinary tract and male reproductive system. This review article explores how neural networks are being used in this field and present research into the use of neural networks for diagnosing, predicting the course and treating urological oncological diseases. The advantages and limitations of using neural networks in this field are demonstrated, and possible directions for future research are suggested. The application of neural networks in oncourology opens new horizons for the development of a personalised approach to diagnosing and treating oncological diseases. Artificial intelligence has the potential to become a powerful tool for improving the accuracy of patient outcome predictions and reducing undesirable side effects of therapy. Introducing neural networks into oncourological practice creates new opportunities for enhancing the work of healthcare organisations and improving the quality of care provided to patients. This can lead to better treatment outcomes and improved patient satisfaction.