The Impact of Conservative Surgical Treatment of Adenomyosis on Fertility and Perinatal Outcomes.

Adenomyosis is a benign condition commonly encountered in patients with infertility. While the definitive surgical management is hysterectomy, conservative surgical management is gaining attention in patients desiring future fertility. This review explores whether the surgical treatment of adenomyosis affects fertility outcomes for patients trying to conceive. The PubMed and Medline databases were searched using the keywords: "adenomyosis", "surgery", "radiofrequency", "infertility", "pregnancy", "sterility", "conception", "miscarriage", and "endometrial receptivity". Abstracts were screened, and relevant articles were selected for review. This review reveals that surgery appears to improve fertility outcomes with or without medical therapy; however, the risk of uterine rupture remains high and the best technique to reduce this risk is still not known. More studies are needed to formulate the best surgical approach for preserving fertility in treating adenomyosis and to establish standardized guidelines.

Robotic surgery for deep-infiltrating endometriosis: is it time to take a step forward?

Endometriosis is a chronic debilitating disease that affects nearly 10% of women of the reproductive age. Although the treatment modalities of endometriosis are numerous, surgical excision of the endometriotic implants and nodules remains the sole cytoreductive approach. Laparoscopic excision of endometriosis was proven to be beneficial in improving the postoperative pain and fertility. Moreover, it was also proved to be safe and efficient in treating the visceral localization of deep endometriosis, such as urinary and colorectal endometriosis. More recently, robotic-assisted surgery gained attention in the field of endometriosis surgery. Although the robotic technology provides a 3D vision of the surgical field and 7-degree of freedom motion, the safety, efficacy, and cost-effectiveness of this approach are yet to be determined. With this paper, we aim to review the available evidence regarding the role of robotic surgery in the management of endometriosis along with the current practices in the field.

Role of depression in blood pressure control. A cross-sectional multicentric study.

RESEARCH PROBLEM: Hypertension is a multifactorial disease that affects approximately one third of the Tunisian adult population. It is a major risk factor for stroke and cardiovascular disease. Environmental and psychosocial factors play an important role in hypertension onset and control. The prevalence of depression among hypertensive patients is 26, 8% and its presence is associated with increased risk of cardiovascular related morbi-mortality. Our study aims to evaluate the role of depression in blood pressure control among ambulatory hypertensive patients. Investigative process: This study is a cross-sectional, multicentric and descriptive study. We intend to include three hundred and two patients. A 24-hour ambulatory blood pressure monitor will be used to evaluate blood pressure control. Depression will be assessed by the 9-item Patient Health Questionnaire (PHQ-9) in Tunisian dialect. Clinical, socio-environmental, psychosocial and therapeutic and prognosis data will be collected from medical records. Patients will be classified into two groups: Controlled versus non-controlled hypertension. PHQ-9 scores will be then compared between the two cohorts. RESEARCH PLAN: Ethical considerations will be undertaken and respected. All patients should express an informed oral consent before enrollment. This trial will run for three months from the 15th August 2022. TRIAL REGISTRATION: NCT05516173.

The Association of Change in Weight During Radiotherapy Treatment With Clinical Outcomes in Patients With Stage I-III Esophageal Cancer.

Esophageal carcinoma (EC) and nutritional status are strongly linked due to swallowing disruptions and treatment-related toxicities. Therefore, malnutrition and weight loss (WL) occur in 85% and 79% of EC patients, respectively. WL is frequently associated with worse EC patient outcomes, however, WL during radiation therapy (RT) and EC patient outcomes have not been well established. The purpose of this study is to retrospectively review the association of WL during RT treatment of EC with clinical outcomes. Non-metastatic EC patients from our institution treated between 2010 and 2018, receiving total prescribed dose >40 Gy and aged >18 years, were included. Patients were analyzed by WL during RT, with categories of ≥5% vs. <5% and ≥10% vs. <10%. Patient characteristics and treatment regimens were similar across all WL groups. In univariate analysis, ≥5% and ≥10% WL were significantly associated with both worse overall survival (OS) and progression-free survival (PFS), and ≥10% WL was significantly associated with increased local recurrence. In multivariate analysis, ≥5% WL was significantly associated with OS and PFS. With both ≥5% and ≥10% WL throughout the radiation treatment being detrimental to OS and PFS. The importance of nutritional support in EC patients receiving radiotherapy is further validated.

Insight into land cover dynamics and water challenges under anthropogenic and climatic changes in the eastern Nile Delta: Inference from remote sensing and GIS data.

The destabilization of delta's worldwide due to climate change and human activities presents challenges in meeting the growing demands for freshwater and food. The Nile Delta in Egypt is a prime example of a vulnerable region facing various stressors. In order to preserve land and water resources, it is crucial to monitor the spatial and temporal changes in Land Use/Land Cover (LULC), shoreline, and Terrestrial Water Storage (TWS) in these vulnerable regions This study comprehensively investigates the dynamic changes in LULC and their associated water and soil responses in the Eastern Nile Delta under these combined impacts. To achieve this goal, a combination of remote sensing techniques utilizing Landsat (5, 8, and 9), and GRACE datasets, along with field observations and Geographic Information System (GIS) tools, was employed. Accordingly, shoreline changes show coastal erosion rates ranging from 5.28 to 34.92 m/year due to climate change-induced SLR, with continued inland movement predicted for the next 20 years. Moreover, the dynamic changes in urbanization and alterations in agricultural cover have considerable penalties for water demand. Analysis of GRACE data indicates a notable reduction in average TWS by 77.89 mm between 2002 and 2017, with an annual rate, estimated at -5.821 mm/year. Soil sampling in highly vulnerable areas confirms agricultural degradation attributed to elevated salinity levels, with EC values ranging from 3.60 to 190 ds/m. These finds provide valuable insights for stakeholders and policymakers, to make reliable strategies regarding water allocation, land use regulations, and climate change adaptation in the worldwide vulnerable deltas.

Surgical Management of Endometriosis Involving the Bladder and Ureter.

BACKGROUND: Endometriosis is a chronic, debilitating condition affecting up to 10% of reproductive-age women. Urinary tract endometriosis is found in 1%-6% of women diagnosed with pelvic endometriosis, with the most common sites being the bladder (70%-85%), ureter (9%-23%), and kidney (4%). Patients typically present with symptoms such as lower abdominal pain, dysuria, and urgency. Unfortunately, urinary tract endometriosis is often asymptomatic, potentially leading to silent obstructive uropathy and kidney failure. OBJECTIVE: To demonstrate a step-by-step approach for the surgical management of urinary tract endometriosis using conventional laparoscopy for partial cystectomy and robotic-assisted laparoscopy for ureteroneocystostomy. MATERIAL AND METHOD: Surgical video of 2 cases managed in an academic tertiary referral center for endometriosis. The first case was a 38-year-old Gravida 3, Para 3 with a history of hysterectomy who had an MRI which revealed a T2 hypointense bladder nodule consistent with endometriosis. Patient had significant urinary urgency, dysuria, and suprapubpic pain that improved but did not disappear after starting oral progestin therapy (5 mg of norethindrone). A cystoscopy was first performed to confirm MRI findings of bladder lesion and to delineate borders and depth of invasion. The second case was a 35-year-old nulliparous woman with chronic pelvic pain and primary infertility. The patient had a history of stage IV endometriosis with deep endometriosis into the bowel and extrinsic encasement of the ureters causing subsequent hydronephrosis requiring bilateral ureteral stents. She had continued daily pelvic pain despite of being on oral contraceptives for medical management of endometriosis. She subsequently underwent bilateral percutaneous nephrostomy tube placement to allow for ureteral rest prior to surgery. RESULTS: In the first case, conventional laparoscopy was utilized to perform bilateral ureterolysis, bladder mobilization, partial cystectomy for complete excision of the lesion, and 2-layered bladder closure. Use of indigo carmine assisted with ureteral orifice identification. In the second case, a cystoscopy was performed with injection of Indocyanine green to assist with ureteral identification. After ureterolysis, distal ureteric obstruction due to extensive disease was confirmed on laparoscopy and ureteroscopy. Bilateral ureteroneocystostomy with placement of Double-J ureteral stents was performed using a robotic-assisted approach. Each patient had an indwelling Foley catheter for bladder decompression during recovery. Pathology in both cases revealed endometriosis. Both patients had an uneventful postoperative course. A postoperative retrograde cystogram confirmed adequate repair prior to removal of each Foley catheter. Patient 2 had uncomplicated office stent removal 6 weeks postoperatively and had a normal renal ultrasound with no hydronephrosis 6 months postoperatively. CONCLUSION: Endometriosis is an increasingly common condition. It is important for gynecological surgeons to have the proper understanding of anatomy, surgical technique, and multidisciplinary care needed with urology for safe and complete excision of bladder and ureter endometriosis.

Enhanced degradation of ibuprofen in an integrated constructed wetland-microbial fuel cell: treatment efficiency, electrochemical characterization, and microbial community dynamics.

Over the past few decades, there has been a growing concern regarding the fate and transport of pharmaceuticals, particularly antibiotics, as emerging contaminants in the environment. It has been proposed that the presence of antibiotics at concentrations typically found in wastewater can impact the dynamics of bacterial populations and facilitate the spread of antibiotic resistance. The efficiency of currently-used wastewater treatment technologies in eliminating pharmaceuticals is often insufficient, resulting in the release of low concentrations of these compounds into the environment. In this study, we addressed these challenges by evaluating how different influent ibuprofen (IBU) concentrations influenced the efficiency of a laboratory-scale, integrated constructed wetland-microbial fuel cell (CW-MFC) system seeded with Eichhornia crassipes, in terms of organic matter removal, electricity generation, and change of bacterial community structure compared to unplanted, sediment MFC (S-MFC) and abiotic S-MFC (AS-MFC). We observed that the addition of IBU (5 mg L-1) resulted in a notable decrease in chemical oxygen demand (COD) and electricity generation, suggesting that high influent IBU concentrations caused partial inhibition for the electroactive microbial community due to its complexity and aromaticity. However, CW-MFC could recover from IBU inhibition after an acclimation period compared to unplanted S-MFC, even though the influent IBU level was increased up to 20 mg L-1, suggesting that plants in CW-MFCs have a beneficial role in relieving the inhibition of anode respiration due to the presence of high levels of IBU; thus, promoting the metabolic activity of the electroactive microbial community. Similarly, IBU removal efficiency for CW-MFC (i.e., 49-62%) was much higher compared to SMFC (i.e., 29-42%), and AS-MFC (i.e., 20-22%) during all experimental phases. In addition, our high throughput sequencing revealed that the high performance of CW-MFCs compared to S-MFC was associated with increasing the relative abundances of several microbial groups that are closely affiliated with anode respiration and organic matter fermentation. In summary, our results show that the CW-MFC system demonstrates suitability for high removal efficiency of IBU and effective electricity generation.

The Present and the Future of Medical Therapies for Adenomyosis: A Narrative Review.

Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments have been proposed, but still, no guidelines directing the management of adenomyosis are available. While a hysterectomy is typically regarded as the definitive treatment for adenomyosis, the scarcity of high-quality data leaves patients desiring fertility with limited conservative options. Based on the available data, the levonorgestrel-IUD appears to offer the most favorable outcomes. Other treatments, including GnRH antagonists, dienogest, prolactin, and oxytocin modulators, show promise; however, further data are required to establish their efficacy definitively. Furthermore, there are many emerging therapies that have been developed that seem worthy of consideration in the near future. The aim of this narrative review was to explore the current medical treatments available for adenomyosis and to provide a glimpse of future therapies under assessment. For this scope, we performed a literature search on PubMed and Medline from incept to September 2022 using the keywords: "medical treatment", "non-steroidal anti-inflammatory", "progesterone intrauterine device", "dienogest", "combined oral contraceptives", "gonadotropin releasing hormone agonist", "gonadotropin releasing hormone antagonist", "danazol", "aromatase inhibitors", "ulipristal acetate", "anti-platelet therapy", "dopamine", "oxytocin antagonists", "STAT3", "KRAS", "MAPK", "micro-RNA", "mifepristone", "valproic acid", "levo-tetrahydropalamatine", and "andrographolide". The search was limited to articles in English, with subsequent screening of abstracts. Abstracts were screened to select relevant studies.

Strategies and factors to maximize cost-effectiveness of robotic surgery in benign gynecological disease.

Operating room procedures account for half of the gross hospital cost in the United States per annum. Hysterectomy is the eighth most common surgery nationally, with more than 300,000 cases every year. Since the introduction of robotic surgery in benign gynecology, concern has been raised regarding the increased cost without significant improvements in outcomes or practice. Surgeon volume, complication rates, length of hospital stay, and selected intraoperative instrumentation are all factors that have a direct effect on cost in robotic surgery. Cost is indirectly influenced by the OR team workflow, postoperative processes to expedite discharge, and converting surgery to the ambulatory setting. More research is needed to develop evidence-based practices for cost containment in robotic surgery.

Adenomyosis: An Updated Review on Diagnosis and Classification.

Adenomyosis is a commonly diagnosed benign condition characterized by the presence of ectopic endometrial glands within the underlying myometrium. The most common presenting signs and symptoms are abnormal uterine bleeding, chronic pelvic pain, and infertility. The clinical relevance of this condition is evident in both medical and surgical care. Histopathology and imaging studies are used for the diagnosis and classification of adenomyosis, which are hallmarks of the advancement of our ability to diagnose adenomyosis. Importantly, the diagnosis and classification of adenomyosis lacks standardization due to the nature of imaging techniques, features of adenomyosis, and the clinical spectrum of adenomyosis. We reviewed the literature to summarize the available classification systems for adenomyosis and highlight the different imaging approaches and histologic criteria used in diagnosis. Despite the high prevalence of the disease, there is no clear consensus on one classification system. We provide a review of some of the classification systems available and discuss their strengths and limitations.

PRMT5 inhibition drives therapeutic vulnerability to combination treatment with BCL-2 inhibition in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an incurable B-cell malignancy that comprises up to 6% of non-Hodgkin lymphomas diagnosed annually and is associated with a poor prognosis. The average overall survival of patients with MCL is 5 years, and for most patients who progress on targeted agents, survival remains at a dismal 3 to 8 months. There is a major unmet need to identify new therapeutic approaches that are well tolerated to improve treatment outcomes and quality of life. The protein arginine methyltransferase 5 (PRMT5) enzyme is overexpressed in MCL and promotes growth and survival. Inhibition of PRMT5 drives antitumor activity in MCL cell lines and preclinical murine models. PRMT5 inhibition reduced the activity of prosurvival AKT signaling, which led to the nuclear translocation of FOXO1 and modulation of its transcriptional activity. Chromatin immunoprecipitation and sequencing identified multiple proapoptotic BCL-2 family members as FOXO1-bound genomic loci. We identified BAX as a direct transcriptional target of FOXO1 and demonstrated its critical role in the synergy observed between the selective PRMT5 inhibitor, PRT382, and the BCL-2 inhibitor, venetoclax. Single-agent and combination treatments were performed in 9 MCL lines. Loewe synergy scores showed significant levels of synergy in most MCL lines tested. Preclinical, in vivo evaluation of this strategy in multiple MCL models showed therapeutic synergy with combination venetoclax/PRT382 treatment with an increased survival advantage in 2 patient-derived xenograft models (P ≤ .0001, P ≤ .0001). Our results provide mechanistic rationale for the combination of PRMT5 inhibition and venetoclax to treat patients with MCL.

PRMT5 supports multiple oncogenic pathways in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an incurable B-cell malignancy with an overall poor prognosis, particularly for patients that progress on targeted therapies. Novel, more durable treatment options are needed for patients with MCL. Protein arginine methyltransferase 5 (PRMT5) is overexpressed in MCL and plays an important oncogenic role in this disease via epigenetic and posttranslational modification of cell cycle regulators, DNA repair genes, components of prosurvival pathways, and RNA splicing regulators. The mechanism of targeting PRMT5 in MCL remains incompletely characterized. Here, we report on the antitumor activity of PRMT5 inhibition in MCL using integrated transcriptomics of in vitro and in vivo models of MCL. Treatment with a selective small-molecule inhibitor of PRMT5, PRT-382, led to growth arrest and cell death and provided a therapeutic benefit in xenografts derived from patients with MCL. Transcriptional reprograming upon PRMT5 inhibition led to restored regulatory activity of the cell cycle (p-RB/E2F), apoptotic cell death (p53-dependent/p53-independent), and activation of negative regulators of B-cell receptor-PI3K/AKT signaling (PHLDA3, PTPROt, and PIK3IP1). We propose pharmacologic inhibition of PRMT5 for patients with relapsed/refractory MCL and identify MTAP/CDKN2A deletion and wild-type TP53 as biomarkers that predict a favorable response. Selective targeting of PRMT5 has significant activity in preclinical models of MCL and warrants further investigation in clinical trials.

Correlation of serum biochemical characteristics and ABCG8 genetic variant (rs 11887534) with gall stone compositions and risk of gallstone disease in Egyptian patients.

BACKGROUND: The overexpression of the cholesterol transporter: ATP-binding cassette transporter (ABCG8) due to the effect of ABCG8 genetic variant (rs11887534) leads to the precipitation of cholesterol crystals and gallstone disease (GSD). OBJECTIVE: To evaluate the chemical composition of gallstones and the role of ABCG8 (rs11887534) in the susceptibility to GSD. METHODS: We enrolled 77 patients with GSD treated with standard laparoscopic or open cholecystectomy and 75 age and sex-matched healthy controls. Chemical analysis of the extracted gallstones was performed. Analysis of the rs11887534 was performed by real-time PCR TaqMan technique for both cases and controls. RESULTS: Pure cholesterol stones were the main type of stones in GSD patients. The CC genotype carriers of rs11887534 were more prone to gallstone formation than other genotypes. The CC genotype carriers were 100 folds at increased risk to develop pure cholesterol stones. CONCLUSION: The most prevalent type of gallbladder stones is pure cholesterol stone. ABCG8 (rs11887534) could be associated with increased risk for cholesterol gallstones formation, this risk was more pronounced in female patients.

Maternal SARS-COV-2 infection and prematurity: the Southern Michigan COVID-19 collaborative.

OBJECTIVE: COVID-19 has been reported to increase the risk of prematurity, however, due to the frequent absence of unaffected controls as well as inadequate accounting for confounders in many studies, the question requires further investigation. We sought to determine the impact of COVID-19 disease on preterm birth (PTB) overall, as well as related subcategories such as early prematurity, spontaneous, medically indicated preterm birth, and preterm labor (PTL). We assessed the impact of confounders such as COVID-19 risk factors, a-priori risk factors for PTB, symptomatology, and disease severity on rates of prematurity. METHODS: This was a retrospective cohort study of pregnant women from March 2020 till October 1st, 2020. The study included patients from 14 obstetric centers in Michigan, USA. Cases were defined as women diagnosed with COVID-19 at any point during their pregnancy. Cases were matched with uninfected women who delivered in the same unit, within 30 d of the delivery of the index case. Outcomes of interest were frequencies of prematurity overall and subcategories of preterm birth (early, spontaneous/medically indicated, preterm labor, and premature preterm rupture of membranes) in cases compared to controls. The impact of modifiers of these outcomes was documented with extensive control for potential confounders. A p value <.05 was used to infer significance. RESULTS: The rate of prematurity was 8.9% in controls, 9.4% in asymptomatic cases, 26.5% in symptomatic COVID-19 cases, and 58.8% among cases admitted to the ICU. Gestational age at delivery was noted to decrease with disease severity. Cases were at an increased risk of prematurity overall [adjusted relative risk (aRR) = 1.62 (1.2-2.18)] and of early prematurity (<34 weeks) [aRR = 1.8 (1.02-3.16)] when compared to controls. Medically indicated prematurity related to preeclampsia [aRR = 2.46 (1.47-4.12)] or other indications [aRR = 2.32 (1.12-4.79)], were the primary drivers of overall prematurity risk. Symptomatic cases were at an increased risk of preterm labor [aRR = 1.74 (1.04-2.8)] and spontaneous preterm birth due to premature preterm rupture of membranes [aRR = 2.2(1.05-4.55)] when compared to controls and asymptomatic cases combined. The gestational age at delivery followed a dose-response relation with disease severity, as more severe cases tended to deliver earlier (Wilcoxon p < .05). CONCLUSIONS: COVID-19 is an independent risk factor for preterm birth. The increased preterm birth rate in COVID-19 was primarily driven by medically indicated delivery, with preeclampsia as the principal risk factor. Symptomatic status and disease severity were significant drivers of preterm birth.

A step-by-step approach to a frozen pelvis.

OBJECTIVE: To demonstrate a step-by-step approach for restoration of pelvic anatomy in frozen pelvis using a systematic approach to make the steps reproducible, safe, and time efficient. DESIGN: Video presentation. SETTING: Academic medical center. PATIENT(S): A 30-year-old nulliparous woman with lifelong dysmenorrhea and 4 years of infertility who presented for the surgical management of stage IV endometriosis. INTERVENTION(S): An abdominopelvic survey was first in a systematic fashion to assess the extent of adhesive disease and evalaute for normal anatomy. Dissection was then started on the patient's left side to mobilize the sigmoid colon at the pelvic brim. Subsequently, the ureters were identified and bilateral ureterolysis was performed as the retroperitoneal spaces were explored. Once the ureters were safely dissected, the adnexa were mobilized bilaterally. Attention was then turned to the dissection of the medial pararectal spaces (Okabayashi's space) before the dissection of the rectovaginal space. With the restoration of anatomy, the remaining planned surgery was completed. MAIN OUTCOMES MEASURE(S): Restoration of pelvic anatomy, excision of endometriosis, and resolution of symptoms. RESULT(S): The patient had an uncomplicated procedure with complete excision of endometriosis and an estimated blood loss of 45 mL. She was discharged on the same day and had an uneventful postoperative period. At her follow-up appointment, she had resolution of symptoms and was initiated on medical hormone suppression therapy until ready for in vitro fertilization. CONCLUSION(S): A frozen pelvis is a condition in which the pelvic organs are distorted and tethered to each other as a result of adhesive processes. This can obscure normal anatomical landmarks and surgical planes making dissection extremely difficult, thus increasing the risk of interoperative and postoperative complications. Although an uncommon surgical condition, it is not rare to come across in clinical practices, thus creating a challenge to reproductive surgeons as it is commonly seen with endometriosis-associated infertility. It is important for surgeons to be able to recognize the relevant anatomy and have the knowledge to open proper pelvic avascular spaces in the pelvis to mitigate these risks. Following this video's step-by-step approach can help restore pelvic anatomy for planned surgical procedures.

Evaluation of vitamin D receptor gene polymorphisms (ApaI and TaqI) as risk factors of vitiligo and predictors of response to narrowband UVB phototherapy.

Vitiligo is acquired depigmentation due to multiple factors. Vitamin D in skin, through its receptors (VDR), regulates cell growth, differentiation, immune response and exerts both stimulatory and protective effects on melanocytes. The gene sequence encoding VDR has polymorphic forms such as ApaI and TaqI that may affect vitamin D actions. Narrowband ultraviolet B (NB-UVB) phototherapy became the mainstay of vitiligo treatment because of its efficacy and little side effects. The current work aimed at evaluating the possible association between VDR gene polymorphisms (TaqI and ApaI) and susceptibility of vitiligo and if they could be predictors of response to NB-UVB phototherapy in Egyptian vitiligo patients. 100 vitiligo patients indicated for NB-UVB phototherapy and 100 healthy age and sex matched controls were included. All participants were subjected to history taking, general and dermatological examinations, and VDR ApaI and TaqI gene polymorphisms analysis by PCR-RFLP. The patients received NB-UVB 3times per week for 6 months then revaluated. There was significant increase in Aa genotype of ApaI polymorphism in patients associated with significant increase in vitiligo activity. 66% of patient showed variable degrees of response to NB-UVB. The responders significantly had AA genotype of ApaI polymorphism. TaqI polymorphism showed nonsignificant effects on vitiligo susceptibility and response to NB-UVB. A allele of ApaI was significant independent predictor of NB-UVB phototherapy responders. VDR gene polymorphism (ApaI) may share in vitiligo pathogenesis and response to NB-UVB. Knowing the genetic background of the patient helps individualization of treatment to get better results.

Efficacy, Safety and Quality of Life of Oxybutynin versus Aluminum Chloride Hexahydrate in Treating Primary Palmar Hyperhidrosis.

Background: Palmar hyperhidrosis is characterized by excessive sweating beyond the physiological needs of the patient's body and the most frequent form is primary or essential. Different treatments protocols have been proposed to control or decrease sweating. Aims and Objectives: This study aimed to compare the efficacy and safety of oral oxybutynin versus topical aluminum chloride hexahydrate (ACH) in treating primary palmar hyperhidrosis. Also, to assess quality of life (QOL) as a measure of improvement of hyperhidrosis state. Materials and Methods: Patients were randomized using the block randomization with sealed envelope method into two treatment groups; oral oxybutynin group and topical ACH group. Hyperhidrosis Disease Severity Scale (HDSS) was used as a primary outcome measure to assess the efficacy of the drug in both groups. Clinical grading and the QOL were used as secondary outcome measures. The safety was evaluated by recording side effects in the follow-up visits. Results: HDSS, clinical grading and QOL score showed a statistically significant improvement in the oral oxybutynin groups. One week after stoppage of treatment, the symptoms recurred again in both groups with return of HDSS and QOL scores to pretreatment levels. The most common side effects were dry mouth (65.8%) and itching (65.0%) for oral oxybutynin group and topical ACH group; respectively. Conclusion: Treatment of primary palmar hyperhidrosis with oxybutynin is a good initial alternative for treatment given that it gives better results and much more improvement in QOL when compared to topical ACH. QOL questionnaire and clinical grading should also be considered as useful tools in the assessment of response to treatment.

Diaphragmatic endometriosis: robotic approaches and techniques.

OBJECTIVE: To present different approaches used in the surgical management of diaphragmatic endometriosis using the Davinci Robotic system. DESIGN: A video article presenting patient positioning, port placement, and surgical techniques used in robotic excision of diaphragmatic endometriosis with concomitant pelvic disease. SETTING: Endometriosis center. PATIENT(S): Patients undergoing excision of diaphragmatic endometriosis. INTERVENTION(S): Systematic robotic approach to excise diaphragmatic lesions depending on the depth of invasion. MAIN OUTCOME MEASURES(S): The advantages and disadvantages of the lithotomy and the lateral decubitus approach were reviewed. Ports placements are illustrated according to the chosen approach. Diaphragmatic peritoneal stripping, diaphragmatic shaving, and diaphragmatic excision are different techniques used according to the depth of invasion. RESULTS(S): N/A. CONCLUSION(S): The choice of approach between the lithotomy position and the left lateral decubitus position depend on the extent of the diaphragmatic disease and the presence of concomitant pelvic lesions. Despite the lack of high-quality evidence, the advantages of the robotic system may improve the outcomes in such difficult cases in comparison with conventional laparoscopy.

TBL1X: At the crossroads of transcriptional and posttranscriptional regulation.

Over the past 2 decades, the adaptor protein transducin ß-like 1 (TBL1X) and its homolog TBL1XR1 have been shown to be upregulated in solid tumors and hematologic malignancies, and their overexpression is associated with poor clinical outcomes. Moreover, dysregulation of the TBL1 family of proteins has been implicated as a key component of oncogenic prosurvival signaling, cancer progression, and metastasis. Herein, we discuss how TBL1X and TBL1XR1 are required for the regulation of major transcriptional programs through the silencing mediator for tetanoid and thyroid hormone receptor (SMRT)/nuclear receptor corepressor (NCOR)/ B cell lymphoma 6 (BCL6) complex, Wnt/ß catenin, and NF-κB signaling. We outline the utilization of tegavivint (Iterion Therapeutics), a first-in-class small molecule targeting the N-terminus domain of TBL1, as a novel therapeutic strategy in preclinical models of cancer and clinically. Although most published work has focused on the transcriptional role of TBL1X, we recently showed that in diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype, genetic knockdown of TBL1X and treatment with tegavivint resulted in decreased expression of critical (onco)-proteins in a posttranscriptional/ß-catenin-independent manner by promoting their proteasomal degradation through a Skp1/Cul1/F-box (SCF)/TBL1X supercomplex and potentially through the regulation of protein synthesis. However, given that TBL1X controls multiple oncogenic signaling pathways in cancer, treatment with tegavivint may ultimately result in drug resistance, providing the rationale for combination strategies. Although many questions related to TBL1X function remain to be answered in lymphoma and other diseases, these data provide a growing body of evidence that TBL1X is a promising therapeutic target in oncology.