A rare case of Whipple disease presenting as a hydrosalpinx and granulomatous peritonitis.

INTRODUCTION: Whipple disease is a rare infectious disease caused by the bacterium Tropheryma whipplei. The classic form affects gastrointestinal and musculoskeletal systems; but other forms may damage the heart, brain, or lungs. Due to non-specific and diverse clinical symptoms, diagnosis of Whipple disease is challenging and often late. Adequate and timely antibiotic treatment is essential for favorable outcome. CASE PRESENTATION: Here we present a case of a young woman admitted to the gynecological clinic for diagnostic laparoscopy for suspected haemato-/hydro- salpinx and peritoneal endometriosis. Macroscopic findings during laparoscopy revealed miliary whitish lesions in the pelvis and histopathology reported granulomatous salpingitis and peritonitis. She was complaining of intermittent abdominal pain, bloating and weight loss. Subsequently, the laparoscopy symptoms worsened and her general condition deteriorated. Differential diagnosis included infective agents such as Mycobacterium tuberculosis; in addition to sarcoidosis, granulomatosis with polyangiitis, and malignancies; all of which were excluded. Finally, Tropheryma whipplei was suspected, and after esophagogastroduodenoscopy with duodenal biopsy, long-term antibiotic treatment was initiated and the patient fully recovered. CONCLUSIONS: Although Whipple disease is rare, it is important to have a high level of awareness for Tropheryma whipplei infection. The localization and course of Whipple's disease may be unpredictable, but a favorable outcome is expected with adequate antibiotic treatment.

Currently Available Treatment Modalities for Uterine Fibroids.

Uterine fibroids (leiomyomas and myomas) are the most common benign gynecological condition in patients presenting with abnormal uterine bleeding, pelvic masses causing pressure or pain, infertility and obstetric complications. Almost a third of women with fibroids need treatment due to symptoms. OBJECTIVES: In this review we present all currently available treatment modalities for uterine fibroids. METHODS: An extensive search for the available data regarding surgical, medical and other treatment options for uterine fibroids was conducted. REVIEW: Nowadays, treatment for fibroids is intended to control symptoms while preserving future fertility. The choice of treatment depends on the patient's age and fertility and the number, size and location of the fibroids. Current management strategies mainly involve surgical interventions (hysterectomy and myomectomy hysteroscopy, laparoscopy or laparotomy). Other surgical and non-surgical minimally invasive techniques include interventions performed under radiologic or ultrasound guidance (uterine artery embolization and occlusion, myolysis, magnetic resonance-guided focused ultrasound surgery, radiofrequency ablation of fibroids and endometrial ablation). Medical treatment options for fibroids are still restricted and available medications (progestogens, combined oral contraceptives andgonadotropin-releasing hormone agonists and antagonists) are generally used for short-term treatment of fibroid-induced bleeding. Recently, it was shown that SPRMs could be administered intermittently long-term with good results on bleeding and fibroid size reduction. Novel medical treatments are still under investigation but with promising results. CONCLUSIONS: Treatment of fibroids must be individualized based on the presence and severity of symptoms and the patient's desire for definitive treatment or fertility preservation.

Uterine Leiomyomas with Specific Histology Features of Two Fumarate Hydratase/Succinate Dehydrogenase-Deficient Tumors: A Double Case Report.

Background and Objectives: Mutations in succinate dehydrogenase (SDH) and fumarate hydratase (FH) give rise to various familial cancer syndromes, with these alterations being characteristic of certain types of histomorphologically specific leiomyomas that hold significant predictive value. Materials and Methods: This study presents two cases of uterine leiomyomas exhibiting rare histomorphological and genetic characteristics, which are crucial for prognosis and further treatment. Results: Distinct histopathological features such as marked nuclear atypia, intracellular eosinophilic globules, and abnormal intratumoral vessels raise suspicion for specific leiomyoma subtypes, which carry predictive significance for additional hereditary cancer syndromes. Immunohistochemical analysis confirmed FH/SDH deficiency in both patients, who underwent careful follow-up. Conclusions: This study describes two cases involving unusual leiomyomas, the histopathological characteristics of which may easily go unrecognized. These features hold predictive significance because their specific mutations point to additional hereditary cancer syndromes, highlighting the need for further examinations.

Induction of TLR5, IRAK1, and NF-κB expression by Trichomonas vaginalis in cervical cancer cell (HeLa) and normal human vaginal epithelial cell (HVECs) lines.

INTRODUCTION: Trichomoniasis is the most common non-viral sexually transmitted infection that increases the risk of cervical cancer. Trichomonas vaginalis (T. vaginalis) can regulate the pro-inflammatory cytokine production in the host cells. Toll-like receptors (TLRs) are a family of the pattern recognition receptors (PRRs) of mammalian cells, expressed in various host cells and have an important role in recognizing pathogens, and pro-inflammatory responses. The aim of the present study is to investigate the role of TLR5 in cervical cancer cells (HeLa) and human vaginal epithelial cells (HVECs) exposed to T. vaginalis. METHODOLOGY: First, the cells and parasites were cultured in RPMI and trypticase yeast extract maltose (TYM), respectively. After adaption of parasite and epithelial cells by RPMI-TYM medium co-culture (9:1 vol/vol), HVECs and HeLa cells were stimulated with T. vaginalis trophozoites (24-hour incubation at 37 °C, 5% CO2). Following RNA extraction and cDNA synthesis, the gene expression levels of TLR5, IRAK1, and NF-κB were assessed using real-time PCR. Besides, the protein levels were measured using western blotting. All tests and controls were normalized using ß-actin as a housekeeping control. RESULTS: Real-time PCR results showed an increased gene expression of TLR5, IRAK1, and NF-κB in T. vaginalis exposed HVECs and HeLa cells compared to the control group (p < 0.05). Additionally, western blot analysis showed a statistically significant increase in TLR5, and NF-κB proteins in both groups after exposure to the parasite (p < 0.05). CONCLUSIONS: These findings provide insight into the host-parasite interaction, and the results indicated that T. vaginalis could stimulate TLR5 and activate related pathways.

Severe Hemoperitoneum due to Ovarian Bleeding after Transvaginal Oocyte Retrieval with Surgical Management: A Retrospective Analysis and Comprehensive Review of the Literature.

Background and Objectives: Severe hemoperitoneum of ovarian bleeding origin is a rare but potentially life-threatening complication of transvaginal oocyte retrieval (TVOR) procedure. The study aimed to present a case series of surgically managed patients from our clinic with hemoperitoneum caused by ovarian bleeding after TVOR, as well as to perform a comprehensive literature review in order to summarize and analyze all published cases with this condition and their management. Materials and Methods: The data of 2939 patients, who underwent TVOR procedures for IVF/ICSI (in vitro fertilization, intracytoplasmic sperm injection) in our clinic between 2010 and 2021 were reviewed. Moreover, a systemic literature search was performed. Main outcome measures from the pooled analysis were incidence and risk factors, type of surgery, intraoperative finding and intervention leading to hemostasis. Results: In our Clinic 4 (0.136%), cases of hemoperitoneum due to ovarian bleeding were surgically managed. Moreover, 39 cases from 18 studies reported in the literature were identified. No risk factors besides lean women with PCOS were identified. In the pooled analysis, the bleeding symptoms appeared in 58.1% of patients within eight hours after TVOR and cumulatively in 81.4% cases during the 24 h after TVOR. The average time from TVOR to surgery was 27.19 ± 53.25 h. Hemostasis was mostly established using electrocoagulation, although few cases of ovariectomy were also reported. Embryo transfer at 60% of cases was postponed and embryos cryopreserved. Conclusions: Severe hemoperitoneum due to ovarian bleeding after TVOR is a rare event that should be treated by techniques of minimally invasive surgery whenever possible. Protocols should be developed to enable optimal management strategies for infertility patients. Embryos obtained should be cryopreserved.

Predictive Value of Basal Serum Progesterone for Successful IVF in Endometriosis Patients: The Need for a Personalized Approach.

The data regarding the role of progesterone (P4) in reproductive events of endometriosis patients are limited. This prospective study aimed to examine the predictive value of basal P4 serum levels for successful in vitro fertilization (IVF) in patients with primary infertility and endometriosis. The study included 73 patients divided according to endometriosis treatment (surgery vs. control-no treatment). The general data, basal hormonal status, and pregnancy rates were determined for every patient. Clinical pregnancy was achieved in 40.3% of patients, and more often in patients treated for endometriosis before IVF. The regression analysis showed that higher basal P4 serum levels were associated with achieving pregnancy through IVF. When regression was adjusted for the patient and IVF characteristics, higher basal P4 serum levels were associated with pregnancy achievement in both groups of women, along with the basal serum levels of FSH, LH, and AMH; EFI score; and stimulation protocol. The ROC analysis showed that the basal P4 serum level for successful IVF should be ≥0.7ng/mL. The basal P4 serum level cut-off for IVF success in endometriosis patients was determined for the first time. Constructed models for IVF success prediction emphasize the importance of determining the basal P4 serum levels for the personalized treatment of endometriosis-related infertility.

Ribosomal protein eL39 is important for maturation of the nascent polypeptide exit tunnel and proper protein folding during translation.

During translation, nascent polypeptide chains travel from the peptidyl transferase center through the nascent polypeptide exit tunnel (NPET) to emerge from 60S subunits. The NPET includes portions of five of the six 25S/5.8S rRNA domains and ribosomal proteins uL4, uL22, and eL39. Internal loops of uL4 and uL22 form the constriction sites of the NPET and are important for both assembly and function of ribosomes. Here, we investigated the roles of eL39 in tunnel construction, 60S biogenesis, and protein synthesis. We show that eL39 is important for proper protein folding during translation. Consistent with a delay in processing of 27S and 7S pre-rRNAs, eL39 functions in pre-60S assembly during middle nucleolar stages. Our biochemical assays suggest the presence of eL39 in particles at these stages, although it is not visualized in them by cryo-electron microscopy. This indicates that eL39 takes part in assembly even when it is not fully accommodated into the body of pre-60S particles. eL39 is also important for later steps of assembly, rotation of the 5S ribonucleoprotein complex, likely through long range rRNA interactions. Finally, our data strongly suggest the presence of alternative pathways of ribosome assembly, previously observed in the biogenesis of bacterial ribosomal subunits.

Reproductive outcomes of IVF after comprehensive endometriosis treatment: a prospective cohort study.

OBJECTIVES: To evaluate the impact of pharmacological and surgical endometriosis treatment on IVF reproductive outcomes in patients with primary infertility. MATERIAL AND METHODS: The study, conducted over a five year period, included 73 patients with endometriosis associated primary infertility subjected to 77 cycles. Group I included patients treated for endometriosis before the IVF (subgroups A: surgical and pharmacological treatment and B: only surgical treatment). Group II included patients immediately subjected to IVF. Assessed outcomes were pregnancy rate (PR) per started cycle, fertilization rate (FR), implantation rate (IR) and live birth rate (LBR). RESULTS: Group IA included 25 patients, Group IB 21 and Group II 27 patients. FR and IR showed no significant differences between groups. PR was significantly higher in the Group I than Group II (49% vs 25%, p = 0.030). PR per started cycle was the highest in the Group IA and the lowest in the Group II (p = 0.040). LBR was significantly higher in whole Group I (p = 0.043) and subgroup IA (p = 0.020) than Group II. Group IA and IB did not differ regarding examined outcomes. Regression analysis showed that endometriosis pretreatment method can impact both achieving pregnancy (p = 0.036) and having a live born child (p = 0.008) after IVF. The combined surgical and pharmacological endometriosis treatment, shorter infertility duration, lower EFI score, using long protocol with FSH+HMG gonadotropins increase the probability of successful IVF. CONCLUSIONS: A combined surgical and pharmacological endometriosis treatment had a positive impact on IVF reproductive outcomes, both on pregnancy and on live birth rates.

Coupling of 5S RNP rotation with maturation of functional centers during large ribosomal subunit assembly.

The protein composition and structure of assembling 60S ribosomal subunits undergo numerous changes as pre-ribosomes transition from the nucleolus to the nucleoplasm. This includes stable anchoring of the Rpf2 subcomplex containing 5S rRNA, rpL5, rpL11, Rpf2 and Rrs1, which initially docks onto the flexible domain V of rRNA at earlier stages of assembly. In this work, we tested the function of the C-terminal domain (CTD) of Rpf2 during these anchoring steps, by truncating this extension and assaying effects on middle stages of subunit maturation. The rpf2Δ255-344 mutation affects proper folding of rRNA helices H68-70 during anchoring of the Rpf2 subcomplex. In addition, several assembly factors (AFs) are absent from pre-ribosomes or in altered conformations. Consequently, major remodeling events fail to occur: rotation of the 5S RNP, maturation of the peptidyl transferase center (PTC) and the nascent polypeptide exit tunnel (NPET), and export of assembling subunits to the cytoplasm.

Investigation of a healthcare-associated Candida tropicalis candidiasis cluster in a haematology unit and a systematic review of nosocomial outbreaks.

BACKGROUND: Non-albicans Candida spp. are an emerging cause of hospital-acquired bloodstream infections, associated with high mortality due to the challenges in diagnosis and delayed treatment. OBJECTIVES: We aimed to investigate a cluster of healthcare-associated invasive candidiasis caused by C tropicalis and review the literature of healthcare-associated outbreaks or clusters caused by C tropicalis. METHODS: An investigation was performed to determine clinical presentation, treatment outcomes and the factors contributing to C tropicalis candidemia occurrence. We searched the Medline database via PubMed and Ovid using the keywords of "Candida tropicalis" combined with "outbreak" or "clustering" or "clusters," and we limited the search to studies conducted from January 1989 to January 2019. RESULTS: We report two related cases of C tropicalis candidemia among patients with AML following a period of neutropenia, who had erythematous skin rash as a first manifesting sign of candidiasis. C tropicalis was isolated from blood and skin cultures of both patients, which were identical by pulsed-field gel electrophoresis typing. Our systematic review of outbreaks caused by C tropicalis suggests that (a) most reported outbreaks have occurred in neonatal and adult ICUs; (b) patients who receive total parenteral therapy, antibiotics and those who have indwelling catheters and recent surgery are at high risk of infection; and (c) environmental and healthcare personnel surveillance suggest that cross-contamination is a major risk factor. CONCLUSION: Control of nosocomial outbreaks caused by C tropicalis should include better infection control measures, education of healthcare professionals especially working in adult and neonatal intensive care and haematology units.

An exceptional case report of disseminated cryptococcosis in a hitherto immunocompetent patient.

Cryptococcosis is an opportunistic fungal infection causes significant disease predominantly in immunocompromised patients. Here we present an excepcional case of disseminated cryptococcosis with pulmonary and cerebral involvement in an immunocompetent patient with no apparent predisposing factors at the time of hospital admission. We described a case of an apparently immunocompetent 66-years old man admitted to hospital with a one-month history of cough, fever and vertigo. During hospitalization, thorax imaging was suggestive of lung metastasis, therefore, he went through several investigations. During hospitalization, he developed neurological symptoms and subsequently underwent a lumbar puncture. Cerebrospinal fluid (CSF) culture was positive for Cryptococcus spp. isolated on Sabouraud's dextrose agar and bird seed agar. In addition, the direct microscopy examination was positive for the India ink test, as well as with the latex agglutination test for cryptococcal polysaccharide antigen (CrAg) in CSF, while serum CrAg was negative. Despite the absence of classic immunocompromising features, he was treated with amphotericin B and fluconazole due to suspected disseminated cryptococcal infection. Later, he was diagnosed with prostatic adenocarcinoma. Upon successful completion of treatment for disseminated cryptococcosis, the patient underwent radical prostate ablation surgery as a treatment forprostatic adenocarcinoma. This exceptional case emphasizes the high degree of suspicion of atypical infections, and in these cases, it is particularly important to consider fungal infections in hitherto healthy patients with no apparent predisposing factors. Although Cryptococcus spp. is predominantly reported in patients with hematological malignancies, cryptococcosis investigation should also be considered as part of the initial workup of patients with a new diagnosis of a solid tumour prior to chemotherapy or radiotherapy.

Management of Orbital Complications of Acute Rhinosinusitis in Pediatric Patients: A 15-Year Single-Center Experience.

BACKGROUND: The major clinical dilemma managing acute rhinosinusitis (ARS) in pediatric population is distinguishing uncomplicated rhinosinusitis from a complicated bacterial ARS and orbital complications, the latter requiring antimicrobials and surgical intervention. However, factors associated with severe orbital complications and the optimum management strategy remains controversial. The objectives of this study were to characterize the clinical outcomes of children with orbital complications of ARS and to identify risk factors associated with disease severity. METHODS: This retrospective cohort analysis evaluated the clinical outcomes of 61 children admitted for orbital complications between January 1, 2002 and December 31, 2017. Descriptive statistics were performed to examine the demographics and clinical findings. We compared groups using Mann-Whitney U test for continuous variables and χ for categorical variables. RESULTS: Although two-thirds of children had received prehospital antibiotics, half of the cohort presented with post-septal orbital complications. While 83% of isolates obtained from the same patients were susceptible to the prehospital antibiotics given, the majority of those who received prehospital antibiotics nevertheless required surgical intervention. We observed significant association between the age of presentation and disease severity. Children >5 years of age presented with more severe orbital complications despite prehospital antibiotics and were more likely to require surgical intervention (P < 0.001). CONCLUSIONS: In this study, stage II/III orbital complications at presentation and older age were the most important determinants of medical treatment failure. Early referral to eye, nose and throat (ENT) should be considered for children >5 years with ARS due to worse orbital complications despite prehospital antibiotics.

A rare case of pacemaker lead endocarditis successfully treated with open heart surgery.

BACKGROUND: Cardiac device-related endocarditis has emerged as a serious complication in the era of advanced medical technology. Pacemaker related infections are rare and life-threatening with incidence from 0.06% to 7% and high mortality rate (30-35%). Diagnosis is hard, frequently delayed and could be even missed due to poor clinical findings. The average delay in diagnosis is 5.5 month. We report a case of the late-onset of pacemaker lead endocarditis caused by S. epidermidis successfully treated with open heart surgery. CASE REPORT: Patient with persistent high fever for 11 month and suspicion for infective endocarditis was admitted in Cardiovascular Institute. No clinical signs of endocarditis were observed. TTE revealed large vegetation 30 × 17 mm attached to the atrial electrodes with high embolic potential. This finding was verified by transesophageal echocardiography (TEE), although CT scan did not reveal vegetation. Blood cultures were negative. A sternotomy with cardiopulmonary bypass was performed and electrodes were extracted with large vegetation. Intraoperative finding revealed large thrombus with vegetation around pacemaker leads. Cultures of the electrodes and vegetation revealed Staphylococcus epidermidis. Surgery was followed up with antibiotic treatment for 6 weeks. He has been followed up for the next 2 years, and without complications. CONCLUSION: The absence of criteria for endocarditis and negative blood cultures should not keep the physician from ruling out lead endocarditis. This complication carries high risk of mortality if left untreated.

Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome.

Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling of the human endometrium. We investigated endometrial mRNA expression of 23 autophagy-related (ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1 (FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin B1), autophagosome elongation (ATG3, ATG5, γ-aminobutyric acid receptor-associated protein - GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were significantly reduced in anovulatory PCOS compared to healthy endometrium. Free androgen index, but not free estrogen index, insulin levels, or body mass index, negatively correlated with the endometrial expression of ATG3, ATG14, and GABARAP in PCOS patients. Treatment of PCOS patients with metformin (2 g/day for 3 months) significantly increased the endometrial mRNA levels of FOXO1, ATG3, and UV radiation resistance-associated gene. These data suggest that increased androgen availability in PCOS is associated with metformin-sensitive transcriptional downregulation of endometrial autophagy.

Premature ovarian failure.

Premature ovarian failure (POF) is the occurrence of hypergonadotropic hypoestrogenic amenorrhea in women under the age of forty years. It is idiopathic in 74-90% patients. Known cases can be divided into primary and secondary POF. In primary POF genetic aberrations can involve the X chromosome (monosomy, trisomy, translocations, deletions) or autosomes. Genetic mechanisms include reduced gene dosage and non-specific chromosome effects impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. Autoimmune ovarian damage is caused by alteration of T-cell subsets and T-cell mediated injury, increase of autoantibody producing B-cells, a low number of effector/cytotoxic lymphocyte, which decreases the number and activity of natural killer cells. Bilateral oophorectomy, chemotherapy, radiotherapy and infections cause the secondary POF. Symptoms of POF include irritability, nervousness, loss of libido, depression, lack of concentration, hot flushes, weight gaining, dry skin, vaginal dryness, frequent infections etc.The diagnosis is confirmed by the level of FSH of over 40 IU/L and estradiol below 50 pmol/L in women aged below 40 years. Biochemical and other hormonal analysis (free thyroxin, TSH, prolactin, testosterone), karyotype (<30 years of age), ultrasound of the breasts and pelvis are advisable. Optimal therapy is combined estrogen progestagen therapy given in a sequential rhythm, after excluding absolute contraindications. Testosterone can be added to adnexectomized women and those with a low libido. Sequential estrogen progestagen replacement therapy is the first line therapy for ovulation induction in those looking for pregnancy and after that oocyte donation will be advised. Appropriate estro-progestagen therapy improves the quality of life and prevents complications such as cardiovascular diseases, osteoporosis, stroke etc.

[Recurrent Fournier's gangrene in a diabetic patient]. / Ponovljena Furijeova gangrena kod bolesnice sa dijabetesom.

INTRODUCTION: Fournier's gangrene (FG) is a fulminant form of infective necrotizing fascitis of the perineal, genital, or perianal regions caused by anorectal or urogenital and perineal trauma, more common in patients with diabetes mellitus and alcohol misuse. Despite contemporary management, mortality is still high and averages 20-30%. CASE OUTLINE: A 53-year-old extremely obese diabetic postmenopausal woman with the history of poorly regulated insulin-dependent diabetes mellitus lasting for 20 years, and gangrene followed by autoamputation of minor labia a year ago, was admitted due to severe suprapubic pain and septic fever. Gynaecological examination revealed suprapubic abscess spontaneously perforated few hours prior to admission. Contraincision was performed and purulent green-yellowish discharge appeared. Microbial evaluation of the obtained specimen identified Peptostreptoccocus, Enterococcus and E.coli. Antibiotics were administered according to the sensitivity test and suprapubic tumour formation was irrigated and drained. The procedure lasted seven days and resulted in the healing of the pathological process. CONCLUSION: FG is still a life-threatening condition; so, diagnosis should be prompt with early surgical intervention, along with antibiotics and good supportive care. Proactive management of the diabetic patient with perineal infections is of extreme importance, in order to prevent the development of FG, the entity associated with very high mortality. According to the literature data available, this is the first reported case of FG relapse.