Assessment of the Impact of SARS-CoV-2 Infection on the Sexual Function of Women, Levels of Oxytocin and Prolactin: A Prospective Cohort Study.

(1) Background: There is a lack of direct evidence on whether SARS-CoV-2 affects women's sexual function through a biological-organic mechanism. Existing studies on the topic are few and have produced contradictory results. This study aims to explore the possible relationship between sex hormones and sexual function in patients who have been infected with SARS-CoV-2. Moreover, we aimed to determine whether these changes are related to the clinical course of COVID-19 and whether they are temporary or long-lasting. (2) Methods: A study was conducted on 104 women, including 64 women infected with COVID-19 and a control group of 40 healthy women, between January 2021 and August 2022. Blood samples were collected to measure prolactin and oxytocin levels, and a clinical assessment was performed 3 and 6 months later. Sexual function self-assessment was captured based on the FSFI scale. (3) Results: Our study found that patients with severe COVID-19 had better sexual satisfaction scores one month after recovery but no discernible difference after six months. High levels of serum prolactin were observed in patients with active COVID-19 but became similar to a control group after one month and remained stable over time. Higher prolactin levels were significantly associated with increased arousal and hydration. Individuals with severe COVID-19 had notably low levels of plasma oxytocin, but there was no correlation between oxytocin levels and sexual satisfaction. (4) Conclusions: The gynecologic symptoms, as well as disturbances in oxytocin and prolactin levels, might be observed in a short time after infection. However, SARS-CoV-2 infection has no lasting effect on sexual function, oxytocin, and prolactin levels among women.

The Potential Influence of Residual or Recurrent Disease on Bevacizumab Treatment Efficacy in Ovarian Cancer: Current Evidence and Future Perspectives.

There were high hopes for the new antiangiogenic medicament, bevacizumab, which could inhibit the creation of new blood vessels through binding to isoform A of vascular endothelial growth factor (VEGF). However, it is not only blood vessels that are responsible for tumor cell spread. During the process of tumor growth, lymphangiogenesis is mediated by other members of the VEGF family, specifically VEGF-C and VEGF-D, which act independent to bevacizumab. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: (1) if the lymph nodes in primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; (2) concerning the second-line treatment, bevacizumab will act in a weakened manner if recurrence occurs in lymph nodes as opposed to a local recurrence; (3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing knowledge gap, which concerns the effect of bevacizumab on metastatic lymph nodes.

Perioperative Factors Affecting the Healing of Rectovaginal Fistula.

Rectovaginal fistula is rare, but a severe complication in gynecology, which despite the effort of clinicians is still not treated successfully in many cases. According to statistics, the healing rates of surgery in patients with RVF range from 20 to 100%. The treatment effectiveness depends on the etiology of fistula, the age of the patients, the presence of comorbidities, the type of surgery and many other factors. Considering the low efficiency of treatment and the high risk of recurrence, the question of possible methods to improve the results occurs. In our review, we analyzed both modifiable and non-modifiable factors which may influence the treatment, healing rate and future fate of the patients. Taking into account all analyzed risk factors, including age, comorbidities, smoking status, microbiology, medications, stoma and stool features, we are aware that rectovaginal fistula's treatment must be individualized and holistic. In cases of poorly healing RVF, the drainage of feces, the use of antibiotic prophylaxis or the implementation of estrogen therapy may be useful. Moreover, microbiome research in women with RVF and towards estrogen therapy should be performed in order to create treatment algorithms in women with fistulae. Those interventions, in our opinion, may significantly improve the outcome of the patients.

Treatment of Vulvovaginal Candidiasis-An Overview of Guidelines and the Latest Treatment Methods.

Vulvovaginal candidiasis (VVC) is a common condition associated with discomfort in affected women. Due to the presence of different forms of the disease, diverse treatment regimens are developed; the newest ones include oteseconazole and ibrexafungerp. Here, we focus on the most up-to-date recommendations regarding VVC treatment, as well as novel treatment options. Topical and oral azoles are the drugs of choice in uncomplicated mycosis. The efficacy of probiotics and substances such as TOL-463 and chlorhexidine is indicated as satisfactory; however, there are no relevant guidelines. Although the majority of researchers agree that the treatment of non-albicans VVC should be long-lasting, the recommendations are inconsistent. Another clinical problem is the treatment of VVC with azole intolerance or resistance, for which literature proposes the use of several drugs including oteseconazole, ibrexafungerp, and voriconazole. The treatment schedules for recurrent VVC include mainly fluconazole; however, alternative options such as immunotherapeutic vaccine (NDV-3A) or designed antimicrobial peptides (dAMPs) were also described. We also focused on VVC affecting pregnant women, which is a substantial challenge in clinical practice, also due to the heterogeneous relevant guidelines. Thus far, few precise recommendations are available in the literature. Future studies should focus on atypical VVC forms to elucidate the inconsistent findings.

Gonadotropin-Releasing Hormone Antagonists-A New Hope in Endometriosis Treatment?

Endometriosis is a chronic disease, in which endometrial-like tissue is found outside the uterine cavity. Lesions are typically located in the true pelvis but can be found, in addition to extragenital endometriosis, in the respiratory system, the diaphragm, the pleura or the pericardium. As the extrauterine endometrial lesions undergo the menstrual cycle, they cause many symptoms, including pain, and besides infertility, they all mostly affect the quality of the patient's life. Pharmacological management of endometriosis significantly increases in importance either as a first-line treatment or as a complementary therapy after surgery. Yet, current research on antagonists of the gonadotropin-releasing hormone (GnRH) has revealed their potential benefits in endometriosis treatment. Their mechanism of action is to down-regulate the hypothalamic-pituitary-gonadal axis and therefore induce a hypoestrogenic state. The resulting reduction of estrogen levels prevents disease progression and diminishes the recurrence rate after surgical removal of endometriosis. The present review summarizes recent reports of the role oral GnRH antagonists have as a significant treatment option for pain reduction in endometriosis patients.

Future Perspectives of Ectopic Pregnancy Treatment-Review of Possible Pharmacological Methods.

Ectopic pregnancy, that is, a blastocyst occurring outside the endometrial cavity of the uterus, affects nearly 2% of pregnancies. The treatment of ectopic pregnancy is surgical or pharmacological. Since surgical management is associated with numerous serious side effects, conservative treatment is sought. The treatment of choice in the majority of cases is based on pharmacotherapy with methotrexate (MTX) in a single- or multi-dose regimen. Although the efficacy of methotrexate reaches between 70 and 90%, its use requires specific conditions regarding both the general condition of the patient and the characteristic features of the ectopic pregnancy. Moreover, MTX can cause severe adverse effects, including stomatitis, hepatotoxicity and myelosuppression. Therefore, clinicians and researchers are still looking for a less toxic, more effective treatment, which could prevent surgeries as a second-choice treatment. Some studies indicate that other substances might constitute a good alternative to methotrexate in the management of ectopic pregnancies. These substances include aromatase inhibitors, especially letrozole. Another promising substance in EP treatment is gefitinib, an inhibitor of EGFR tyrosine domain which, combined with MTX, seems to constitute a more effective alternative in the management of tubal ectopic pregnancies. Other substances for local administration include KCl and absolute ethanol. KCl injections used in combination with MTX may be used when foetal heart function is detected in cervical ectopic pregnancies, as well as in heterotopic pregnancy treatment. Absolute ethanol injections proved successful and safe in caesarean scar pregnancies management. Thus far, little is known about the use of those substances in the treatment of ectopic pregnancies, but already conducted studies seem to be promising.

Integration of local and systemic immunity in ovarian cancer: Implications for immunotherapy.

Cancer is a disease that induces many local and systemic changes in immunity. The difficult nature of ovarian cancer stems from the lack of characteristic symptoms that contributes to a delayed diagnosis and treatment. Despite the enormous progress in immunotherapy, its efficacy remains limited. The heterogeneity of tumors, lack of diagnostic biomarkers, and complex immune landscape are the main challenges in the treatment of ovarian cancer. Integrative approaches that combine the tumor microenvironment - local immunity - together with periphery - systemic immunity - are urgently needed to improve the understanding of the disease and the efficacy of treatment. In fact, multiparametric analyses are poised to improve our understanding of ovarian tumor immunology. We outline an integrative approach including local and systemic immunity in ovarian cancer. Understanding the nature of both localized and systemic immune responses will be crucial to boosting the efficacy of immunotherapies in ovarian cancer patients.

Ibrutinib in the Treatment of Solid Tumors: Current State of Knowledge and Future Directions.

Bruton's Tyrosine Kinase (BTK) is considered crucial in the activation and survival of both physiological and malignant B-cells. In recent years, ibrutinib, an oral BTK inhibitor, became a breakthrough therapy for hematological malignancies, such as chronic lymphocytic. However, ibrutinib's feasibility might not end there. Several other kinases with established involvement with solid malignancies (i.e., EGFR, HER2) have been found to be inhibited by this agent. Recent discoveries indicate that BTK is a potential anti-solid tumor therapy target. Consequently, ibrutinib, a BTK-inhibitor, has been studied as a therapeutic option in solid malignancies. While most preclinical studies indicate ibrutinib to be an effective therapeutic option in some specific indications, such as NSCLC and breast cancer, clinical trials contradict these observations. Nevertheless, while ibrutinib failed as a monotherapy, it might become an interesting part of a multidrug regime: not only has a synergism between ibrutinib and other compounds, such as trametinib or dactolisib, been observed in vitro, but this BTK inhibitor has also been established as a radio- and chemosensitizer. This review aims to describe the milestones in translating BTK inhibitors to solid tumors in order to understand the future potential of this agent better.

Preoperative Differentiation of Uterine Leiomyomas and Leiomyosarcomas: Current Possibilities and Future Directions.

The distinguishing of uterine leiomyosarcomas (ULMS) and uterine leiomyomas (ULM) before the operation and histopathological evaluation of tissue is one of the current challenges for clinicians and researchers. Recently, a few new and innovative methods have been developed. However, researchers are trying to create different scales analyzing available parameters and to combine them with imaging methods with the aim of ULMs and ULM preoperative differentiation ULMs and ULM. Moreover, it has been observed that the technology, meaning machine learning models and artificial intelligence (AI), is entering the world of medicine, including gynecology. Therefore, we can predict the diagnosis not only through symptoms, laboratory tests or imaging methods, but also, we can base it on AI. What is the best option to differentiate ULM and ULMS preoperatively? In our review, we focus on the possible methods to diagnose uterine lesions effectively, including clinical signs and symptoms, laboratory tests, imaging methods, molecular aspects, available scales, and AI. In addition, considering costs and availability, we list the most promising methods to be implemented and investigated on a larger scale.

Dietary Supplements in Chemotherapy-Induced Peripheral Neuropathy: A New Hope?

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the main and most prevalent side effects of chemotherapy, significantly affecting the quality of life of patients and the course of chemotherapeutic treatment. Nevertheless, despite its prevalence, the management of the CIPN is considered particularly challenging, with this condition often being perceived as very difficult or even impossible to prevent with currently available agents. Therefore, it is imperative to find better options for patients diagnosed with this condition. While the search for the new agents must continue, another opportunity should be taken into consideration-repurposing of the already known medications. As proposed, acetyl-L-carnitine, vitamins (group B and E), extracts of medical plants, including goshajinkigan, curcumin and others, unsaturated fatty acids, as well as the diet composed of so-called "sirtuin-activating foods", could change the typical way of treatment of CIPN, improve the quality of life of patients and maintain the continuity of chemotherapy. This review summarizes currently available data regarding mentioned above agents and evaluates the rationale behind future research focused on their efficacy in CIPN.

Age related changes in brain MR appearance in the course of neurocutaneous melanosis.

BACKGROUND: Patients with giant congenital melanocytic nevi (GCMN) have increased risk of neurocutaneous melanosis (NCM). Brain MRI is mandatory in GCMN. OBJECTIVES: To present the age related changes in brain MRI in children with NCM during several-year follow-up. METHODS: In 7 NCM children following data were analyzed: main nevus localization, surgical treatment phase, histology of excised nevi, time of NCM diagnosis, number of MRI studies, neurological symptoms, changes of melanin deposits in brain during follow-up. RESULTS: Four children had bathing trunk nevus, two main nevus on back, one on head. Surgical excision is finished in 3 patients, 4 are in the course of multistage surgery. In one melanoma arising in GCMN was diagnosed. Six patients are neurologically healthy, one suffers from seizures. Age of patients at first MRI ranged from 12days to 7 years. All patients underwent more than one MRI. Follow-up period ranges from 2.5 to 8.5 years. Most of T1-hyperintense foci in brains regressed with time. In one case new lesion appeared, in one more lesions were visible on second MRI. CONCLUSIONS: In all patients with NCM on subsequent MRI image changes were found with respect to original location and size of melanin deposits in CNS. Changes of NCM appearance on MRI with advancing age of patients reflect natural history of this disorder. Theory of gradual disappearance of intracerebral melanin deposits with age seems to be more likely than theory of their worse visualization on MRI with time.

Giant congenital melanocytic nevi: selected aspects of diagnostics and treatment.

BACKGROUND: Treatment of giant melanocytic nevi (GMN) remains a multidisciplinary challenge. We present analysis of diagnostics, treatment, and follow- up in children with GMN to establish obligatory procedures in these patients. MATERIAL/METHODS: In 24 children with GMN, we analyzed: localization, main nevus diameter, satellite nevi, brain MRI, catecholamines concentrations in 24-h urine collection, surgery stages number, and histological examinations. The t test was used to compare catecholamines concentrations in patient subgroups. RESULTS: Nine children had "bathing trunk" nevus, 7 had main nevus on the back, 6 on head/neck, and 2 on neck/shoulder and neck/thorax. Brain MRI revealed neurocutaneous melanosis (NCM) in 7/24 children (29.2%), symptomatic in 1. Among urine catecholamines levels from 20 patients (33 samples), dopamine concentration was elevated in 28/33, noradrenaline in 15, adrenaline in 11, and vanillylmandelic acid in 4. In 6 NCM children, all catecholamines concentrations were higher than in patients without NCM (statistically insignificant). In all patients, histological examination of excised nevi revealed compound nevus, with neurofibromatic component in 15 and melanoma in 2. They remain without recurrence/metastases at 8- and 3-year-follow-up. There were 4/7 NCM patients with more than 1 follow-up MRI; in 1 a new melanin deposit was found and in 3 there was no progression. CONCLUSIONS: Early excision with histological examination speeds the diagnosis of melanoma. Brain MRI is necessary to confirm/rule-out NCM. High urine dopamine concentration in GMN children, especially with NCM, is an unpublished finding that can indicate patients with more serious neurological disease. Treatment of GMN children should be tailored individually for each case with respect to all medical/psychological aspects.

[Surgical treatment of neonates with very low (VLBW) or extremely low (ELBW) birth weight].

UNLABELLED: Progress in perinatology and neonatal intensive care led to surgical treatment of premature infants born with low (<1500 g) and extremely low (<1000 g) birth weight. AIM: Evaluation of surgical treatment in the group of neonates with very low birth weight (<1500 g) and extremely low birth weight (<1000 g). MATERIAL AND METHODS: In the years 2000-2009 in the Department of Paediatric Surgery in the Institute of Mother and Child, 617 neonates underwent surgical treatment, 101 of them (16%) were born with very low or extremely low birth weight. In the analyzed group the birth weight ranged from 450 g to 1500 g (mean 952 g), gestational age ranged from 23 weeks to 32 weeks (mean 27 weeks). Fifty four patients (53%) were operated with the weight <1000 g. Indications for surgery were of two categories: pathologies related to prematurity and congenital defects. The extend of surgical intervention is presented. Additional pathologies influencing prognosis such as respiratory distress syndrome, haemodynamic ductus arteriosus, intraventricular haemorrhagia, multiple congenital defects and genetic disorders were also taken into consideration. Mortality in the entire group of patients was evaluated in relation to the birth weight, gestational age, reasons for surgical treatment and additional risk factors. RESULTS: Pathologies related to prematurity were indications for surgical treatment in 70 patients: perforation of the bowel in the course of necrotizing enterocolitis - NEC (28 patients), spontaneous intestinal perforation - SIP (32), gastric perforation - GP (4), meconium obstruction - MO (3) posthemorrhagic hydrocephalus - PH (3). In the remaining 31 neonates the following congenital defects were operated: inguinal hernia (10 patients), oesophageal atresia (8), anal atresia (2), torsion of the bowel (2), bowel atresia (3), hernia of the umbilical cord (3), ruptured omphalocele (1), myelomeningocele (2). In the entire group of 101 premature infants, 99 patients (98%) had respiratory distress syndrome, 56 (56%) required the closure of ductus arteriosus , in 55 patients (55%) intraventricular haemorrhage from II to IV degree was confirmed. In total thirty patients died. Twenty one of them were ELBW neonates. None of the patients died during the operation or within the first postoperative day. Mortality rate in the group with the weight <1000 g was 38%, in the group with the weight 1000 g-1500 g it was 19%. Highest mortality was observed in the patients with oesophageal atresia (62%) In this group the biggest number of additional anomalies or other genetic disorders was found. Twenty infants died (31%) in the group of 64 neonates with perforations. Mortality rate in the groups with the weight <1000 g and 1000 g-1500 g it was 34% and 26% respectively. Our results confirmed the significant difference between mortality in NEC - 65% and in SIP - 19.5% . The remaining 5 deaths were related both to extreme multiorgan prematurity and severe congenital defects. CONCLUSION: The most frequent indications for surgery in premature neonates (VLBW and ELBW) are acquired pathologies which are related to premature multiorgan insufficiency: perforations in the course of ischaemic or inflamatory changes in the bowel (NEC, SIP), intestinal obstruction related to functional insufficiency of alimentary tract (MO) and posthaemorrhagic hydrocephalus. Congenital anomalies constitute 30% of indications for surgical treatment in this group of patients. Neonates born with low or extremely low birth weight are in the group of patients with the highest intraoperative risk. There is herefore a need to create well equipped, interdisciplinary centres employing paediatric surgeons, anaesthesiologists and neonatologists experienced in treatment of extremely premature neonates.