Pharmacotherapy in Stress Urinary Incontinence; A Literature Review.

PURPOSE OF REVIEW: Stress urinary incontinence (SUI) is a commonly observed condition in females, as well as in males who have undergone prostatectomy. Despite the significant progress made in surgical techniques, pharmacotherapy has not yielded substantial outcomes within the clinical domain. This review aims to present a comprehensive overview of the existing pharmacotherapy options for stress urinary incontinence (SUI) and the emerging therapeutic targets in this field. RECENT FINDINGS: One meta-analysis demonstrated that α-adrenergic medications are more efficacious in improving rather than curing SUI symptoms. One trial showed reduced pad weight gain with PSD-503, a locally administered α-adrenergic receptor agonist. New data show that duloxetine's risk outweighs its benefits. One small-scale trial was found to support the use of locally administered estriol in improving subjective outcomes. Emerging targets include serotonin 5HT2C agonists, selective inhibitors of norepinephrine uptake, and myostatin inhibitors. Only one of the evaluated drugs, duloxetine, has been approved by some countries. Currently, trials are evaluating novel targets. Systemic adverse effects such as gastrointestinal upset with duloxetine and orthostatic hypotension with α-adrenoceptor agonists have hampered the efficacy of drugs used to treat SUI in women and men.

Ultra-mini Percutaneous Nephrolithotomy (UM-PCNL) with a Semi-rigid Ureteroscope in Preschool Children: An Innovative Experience in Southern Iran.

PURPOSE: Percutaneous nephrolithotomy (PCNL) has undergone extensive modification to reduce complications. One of the recent advances in minimally invasive procedures is the advent of ultra-mini PCNL (UM-PCNL), which provides miniaturized access to the kidney. However, the specific instruments applied in UM-PCNL may not be found in centers with limited resources. This study evaluated the safety, feasibility, results, and short-term complication rates of performing UM-PCNL using a semi-rigid ureteroscope in preschool children. MATERIALS AND METHODS: Between September 2013 and September 2021, a total of 68 patients, including 42 boys and 26 girls with a mean age of 3.2 ± 2.4 years, underwent UM-PCNL with a 4.5French tip ureteroscope instead of an ultra-mini nephroscope in children aged less than 7 years old. The procedure was done under general anesthesia in the prone position. The nephrostomy tract was dilated to 12F. Stones were fragmented using a pneumatic lithotripter. Irrigation was done with normal saline. RESULTS: The early stone-free rate (SFR) was 91%, and the short-term total SFR was 97%. No statistically significant difference was found in pre-operative and post-operative Hb, BUN, Cr, Na+, and K+. Fever (11 patients) and ileus (5 patients) constituted the majority of complications, and only one patient required a blood transfusion. None of the cases undergoing UM-PCNL with this method required a re-do PCNL. CONCLUSION: Our experience shows that with sufficient experience in handling semi-rigid ureteroscopes, urologists practicing in centers with limited resources could perform UM-PCNL with relatively favorable outcomes.

Testosterone replacement therapy in patients with cachexia: a contemporary review of the literature.

INTRODUCTION: Patients with long-term chronic illnesses frequently present with hypogonadism, which is primarily managed through exogenous testosterone. These same patients also experience a high degree of cachexia, a loss of skeletal muscle and adipose tissue. OBJECTIVE: To perform a contemporary review of the literature to assess the effectiveness of testosterone replacement therapy (TRT) for managing chronic disease-associated cachexia. METHODS: We performed a PubMed literature search using MeSH terms to identify studies from 2000 to 2022 on TRT and the following cachexia-related chronic medical diseases: cancer, COPD, HIV/AIDS, and liver cirrhosis. RESULTS: From the literature, 11 primary studies and 1 meta-analysis were selected. Among these studies, 3 evaluated TRT on cancer-associated cachexia, 3 on chronic obstructive pulmonary disease, 4 on HIV and AIDS, and 2 on liver cirrhosis. TRT showed mixed results favoring clinical improvement on each disease. CONCLUSIONS: Cachexia is commonly observed in chronic disease states. Its occurrence with hypogonadism, alongside the shared symptoms of these 2 conditions, points toward the management of cachexia through the administration of exogenous testosterone. Robust data in the literature support the use of testosterone in increasing lean body mass, improving energy levels, and enhancing the quality of life for patients with chronic disease. However, the data are variable, and further studies are warranted on the long-term efficacy of TRT in patients with cachexia.

Case report: A case of renal arcuate vein thrombosis successfully treated with direct oral anticoagulants.

A rare case of a 35 years old woman presented with renal arcuate vein thrombosis (RAVT) and acute kidney injury (AKI) following upper respiratory tract symptoms and toxic substance ingestion. Histopathological evaluation of the patient's kidney tissue indicated a rare venous thrombosis in the renal arcuate veins. Anticoagulation with Apixaban, a direct oral anticoagulant (DOAC), was commenced, and the patient's symptoms resolved during the hospital stay. Hitherto, a limited number of studies have shown the concurrent presentation of RAVT and overt AKI in patients following ingestion of nephrotoxic agents. Further studies are necessary to elucidate the etiology, clinical presentation, and treatment of RAVT. We suggest that Apixaban be studied as a suitable alternative to conventionally used anti-coagulants such as Warfarin in patients who lack access to optimal health care facilities.

Malignant priapism: case report and update on management protocols.

Background: Malignant priapism, a rare disease with only about 500 reported cases to date, consists of persistent erection secondary to invasion or metastasis of a primary neoplasm. While treatment guidelines for priapism in non-malignant cases have been established, there is currently no guideline for treating malignant priapism. Herein, we describe three cases of malignant priapism and suggest a step-by-step approach for clinical management. Case Description: This study reports three cases of malignant priapism resulting from advanced genitourinary cancers. All patients experienced a sub-acute progression of penile pain and ultimately underwent palliative penectomy, resulting in sustained symptom relief. Conclusions: Treatment of malignant priapism needs to be individualized to the needs of the patient. No matter the primary or secondary nature of the disease, current data suggest that malignant priapism is associated with poor outcomes and emphasis should be put on palliative care. Similar to previous cases, our cases died shortly after the diagnosis of malignant priapism. Conventional procedures such as shunting may not necessarily provide symptom relief in these patients. Although new radiation techniques have shown favorable outcomes, penectomy should be considered the last resort in clinical management. Revisions to the existing management guidelines for priapism are necessary to address its occurrence in malignant contexts.

Association of Epidermal Growth Factor 61A>G, Survivin -31G>C, and EFNA1 -1732G>A Polymorphisms with Susceptibility to Colorectal Cancer.

BACKGROUND: Genetic polymorphisms play an important role in the development of colorectal cancer (CRC). Functional variants in the epidermal growth factor (EGF), survivin, and Ephrin A1 (EFNA1) genes have been previously reported to play a potential role in susceptibility to CRC, but these polymorphisms have not been well replicated. The aim of this study was to assess the association of the EGF 61A>G, Survivin -31G>C, and EFNA1 -1732G>A polymorphisms with the susceptibility to CRC in an Iranian population. METHODS: A total of 148 cases diagnosed with CRC and 160 healthy subjects were recruited. The EGF 61A>G, survivin -31G>C, and EFNA1 -1732G>A polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: Our data revealed that the homozygous mutant genotype (CC: OR = 2.895, 95% CI = 1.092-7.673, p = 0.033) and mutant allele (C: OR = 1.629, 95% CI = 1.152-2.303, p = 0.006) of the survivin -31G>C were associated with an increased risk of CRC in the Iranian population. However, our results failed to show an association between the EGF 61A>G and EFNA1 -1732G>A polymorphisms and CRC risk. CONCLUSION: Our results revealed that the survivin -31G>C polymorphism might play an important role in development of CRC in Iranian population. However, no association of EGF 61A>G and EFNA1 -1732G>A polymorphisms with CRC risk was found.

MCM2 mutation causes autosomal dominant nonsyndromic hearing loss (DFNA70): novel variant in the second family.

Pathogenic variants in MCM2 could result in mild to severe sensorineural hearing loss in the affected individuals (deafness, autosomal dominant 70; DFNA70; OMIM: 616968), an extremely rare autosomal dominant progressive disorder. Here, we report a novel missense variant (NM_004526:c.388C>T, p.R130C; Clinvar: SCV002072508) in MCM2 in an Iranian family identified by whole-exome sequencing and confirmed by Sanger sequencing. The heterozygous variant (NM_004526:c.388C>T, p.R130C) in MCM2 was identified in the proband and his mother. The proband is a nine-year-old male born to nonconsanguineous parents. The proband was characterized by nonsyndromic hearing loss, while his mother showed a mild form of the disorder. This study reports the second disease-causing variant in MCM2 in the world and confirms that hearing loss arising from variants in MCM2 is nonsyndromic. Nevertheless, as was reported in the previous family, phenotype could vary among the patients with the same variant.

A pathogenic variant of TULP3 causes renal and hepatic fibrocystic disease.

Patient variants in Tubby Like Protein-3 (TULP3) have recently been associated with progressive fibrocystic disease in tissues and organs. TULP3 is a ciliary trafficking protein that links membrane-associated proteins to the intraflagellar transport complex A. In mice, mutations in Tulp3 drive phenotypes consistent with ciliary dysfunction which include renal cystic disease, as part of a ciliopathic spectrum. Here we report two sisters from consanguineous parents with fibrocystic renal and hepatic disease harboring a homozygous missense mutation in TULP3 (NM_003324.5: c.1144C>T, p.Arg382Trp). The R382W patient mutation resides within the C-terminal Tubby domain, a conserved domain required for TULP3 to associate with phosphoinositides. We show that inner medullary collecting duct-3 cells expressing the TULP3 R382W patient variant have a severely reduced ability to localize the membrane-associated proteins ARL13b, INPP5E, and GPR161 to the cilium, consistent with a loss of TULP3 function. These studies establish Arginine 382 as a critical residue in the Tubby domain, which is essential for TULP3-mediated protein trafficking within the cilium, and expand the phenotypic spectrum known to result from recessive deleterious mutations in TULP3.

A novel PTRH2 missense mutation causing IMNEPD: a case report.

PTRH2 deficiency is associated with an extremely rare disease, infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). We report the first Iranian patient with IMNEPD. We detected a pathogenic variant in the PTRH2 gene (NM_016077.5: c.68T > C, p.V23A). The proband has myopia, spastic diplegic cerebral palsy, urolithiasis, and a history of seizures.

Vitiligo and Rise in Blood Pressure - a Case-Control Study in a Referral Dermatology Clinic in Southern Iran.

PURPOSE: Vitiligo is an acquired hypopigmentation condition in which well-defined macules can develop virtually everywhere on the patients' skin. This analytic case-control study was conducted in Faghihi Hospital outpatient dermatology clinic, affiliated to Shiraz University of Medical Sciences, southern Iran from June to September 2019. Furthermore, we studied the relationship of hypertension with activity, age of onset, duration, affected body surface area and type of vitiligo. PATIENTS AND METHODS: In the current case-control study, 166 individuals were enrolled in total (the case group was comprised of 83 vitiligo patients and 83 individuals actedas control group). The case group was made up of vitiligo patients (both segmental and non-segmental) between 20 and 50 years of age, no prior history of systemic disease and other hypopigmentation disorders, while individuals with any form of dermatologic findings were excluded from the control group. Individuals aged younger than 20 years old or older than 50, having a dermatologic disease other than vitiligo, being afflicted with the diseases which may lead to secondary hypertension, pregnancy, taking substances, and medication which can lead to hypertension were chosen as the exclusion criteria in this study. RESULTS: Data obtained from our study revealed that vitiligo patients had a higher prevalence of essential hypertension diagnosis than the control group (P=0.040). Also, no significant relationship was found between patients' age at the first lesion appearance (P=0.856), duration of vitiligo involvement (P=0.497), and percentage of vitiligo involvement (P=0.681) with hypertension. CONCLUSION: According to our results, vitiligo patients were more susceptible to hypertension while no association could be found between characteristics of the disease and rise in blood pressure.