Urachal mucinous cystic tumor of low malignant potential in a polymorbid female: a case report and review of the literature

Neoplasms of the urachus are exceedingly rare, representing 0.17% of all bladder cancers. The mucinous cystic tumor of low malignant potential (MCTLMP) subtype is particularly rare with just 25 previous cases reported in the literature. Although rare, MCTLMPs are important to identify due to potential devastating complications and good cure rates with surgical removal. We present a 43 year old female with a nuanced constellation of comorbidities and confirmed MCTLMP following a workup for abdominal pain and irritative lower urinary tract symptoms. Notably, this tumor did not change in size over a 3-year course of serial imaging prior to surgical excision. This urachal MCTLMP represents roughly the 26th and one of the smallest of its subtype reported in the literature. This case illustrates the diagnosis and management of this rare urachal MCTLMP. Individual patient medical history, clinical considerations, and neoplasm characteristics are examined. Although rare, the potential for increased malignancy and potential complications necessitates surgical management and further investigation by the academic community.

A Novel 2-Carbon-Linked Dimeric Artemisinin With Potent Antileukemic Activity and Favorable Pharmacology

Acute myeloid leukemia (AML) remains a devastating disease, with low cure rates despite intensive standard chemotherapy regimens. In the past decade, targeted antileukemic drugs have emerged from research efforts. Nevertheless, targeted therapies are often effective for only a subset of patients whose leukemias harbor a distinct mutational or gene expression profile and provide only transient antileukemic responses as monotherapies. We previously presented single agent and combination preclinical data for a novel 3-carbon-linked artemisinin-derived dimer (3C-ART), diphenylphosphate analog 838 (ART838), that indicates a promising approach to treat AML, given its demonstrated synergy with targeted antileukemic drugs and large therapeutic window. We now report new data from our initial evaluation of a structurally distinct class of 2-carbon-linked dimeric artemisinin-derived analogs (2C-ARTs) with prior documented in vivo antimalarial activity. These 2C-ARTs have antileukemic activity at low (nM) concentrations, have similar cooperativity with other antineoplastic drugs and comparable physicochemical properties to ART838, and provide a viable path to clinical development.

Therapeutical interference with the epigenetic landscape of germ cell tumors: a comparative drug study and new mechanistical insights

Background Type II germ cell tumors (GCT) are the most common solid cancers in males of age 15 to 35 years. Treatment of these tumors includes cisplatin-based therapy achieving high cure rates, but also leading to late toxicities. As mainly young men are suffering from GCTs, late toxicities play a major role regarding life expectancy, and the development of therapy resistance emphasizes the need for alternative therapeutic options. GCTs are highly susceptible to interference with the epigenetic landscape; therefore, this study focuses on screening of drugs against epigenetic factors as a treatment option for GCTs. Results We present seven different epigenetic inhibitors efficiently decreasing cell viability in GCT cell lines including cisplatin-resistant subclones at low concentrations by targeting epigenetic modifiers and interactors, like histone deacetylases (Quisinostat), histone demethylases (JIB-04), histone methyltransferases (Chaetocin), epigenetic readers (MZ-1, LP99) and polycomb-repressive complexes (PRT4165, GSK343). Mass spectrometry-based analyses of the histone modification landscape revealed effects beyond the expected mode-of-action of each drug, suggesting a wider spectrum of activity than initially assumed. Moreover, we characterized the effects of each drug on the transcriptome of GCT cells by RNA sequencing and found common deregulations in gene expression of ion transporters and DNA-binding factors. A kinase array revealed deregulations of signaling pathways, like cAMP, JAK-STAT and WNT. Conclusion Our study identified seven drugs against epigenetic modifiers to treat cisplatin-resistant GCTs. Further, we extensively analyzed off-target effects and modes-of-action, which are important for risk assessment of the individual drugs.

Efficacy of fluoroquinolones as substitutes for ethambutol or rifampin in the treatment of Mycobacterium avium complex pulmonary disease according to radiologic types

Objective: During the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD), ethambutol or rifampin is often discontinued because of adverse events. This study investigated the treatment outcomes when later-generation fluoroquinolones substitute ethambutol or rifampin in MAC-PD treatment based on the radiologic type. Methods: Between 2006 and 2019, patients who initiated standard treatment and whose treatment duration was ≥1 year were retrospectively identified at a tertiary referral center in South Korea, including 178 patients with cavitary disease (fibrocavitary and cavitary nodular bronchiectatic types) and 256 patients with noncavitary nodular bronchiectatic (NC-NB) type. We compared the microbiologic cure at 1 year between the patients who maintained the initial regimen and those who replaced ethambutol or rifampin with fluoroquinolones (moxifloxacin or levofloxacin). Results: The overall microbiologic cure rate of the 178 patients with cavitary disease was 71.3%. Among these, the microbiologic cure rates of the 16 patients who substituted fluoroquinolones for ethambutol were lower than those of the 156 patients who maintained three-drug oral antibiotics with aminoglycoside (37.5% vs. 74.4%, respectively; P = 0.007), which was statistically significant in multivariate analysis. The outcomes of the six patients receiving fluoroquinolones as an alternative to rifampin were similar to that of those continuing the initial regimen. The microbiologic cure rate of the patients with the NC-NB type receiving daily or intermittent oral three-drug therapy was similar regardless of maintaining the initial therapy or replacing ethambutol or rifampin with fluoroquinolones. Conclusions: In cavitary MAC-PD, substituting ethambutol with fluoroquinolones resulted in inferior patient outcomes.

Fecal Microbiota Transplant in Severe and Non-Severe Clostridioides difficile Infection. Is There a Role of FMT in Primary Severe CDI?

Background: Faecal microbiota transplant (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) with cure rates ranging between 85 and 92%. The FMT role for primary Clostridioides difficile infection (CDI) has yet to be settled because of limited data and small-sample studies presented in the current literature. Our study goals were to report the risk factors and the risk of recurrence after FMT for each CDI episode (first, second, and third) and to explore if there is a role of FMT in primary severe CDI. Methods: We conducted a retrospective study to analyze the clinical characteristics and the outcomes of 96 FMT patients with a prior 10 day course of antibiotic treatment in the medical records, of which 71 patients with recurrent CDI and 25 patients with a primary CDI. Results: The overall primary cure rate in our study was 88.5% and the primary cure rate for the severe forms was 85.7%. The data analysis revealed 5.25%, 15.15%, and 27.3% FMT recurrence rates for primary, secondary, and tertiary severe CDI. The risk of recurrence was significantly associated with FMT after the second and the third CDI severe episodes (p < 0.05), but not with FMT after the first severe CDI episode. Conclusions: This study brings new data in supporting the FMT role in CDI treatment, including the primary severe CDI, however, further prospective and controlled studies on larger cohorts should be performed in this respect.

Retrospective analysis of the role of intra-operative parathyroid hormone monitoring during parathyroidectomy for primary hyperparathyroidism; a single center experience over 2 decades

Background: The role of intra-operative parathyroid hormone (IOPTH) monitoring during parathyroidectomy for primary hyperparathyroidism has long been debated. Objectives: Our main goal was to investigate the cure rates of parathyroidectomy for primary hyperparathyroidism with and without IOPTH monitoring. Our secondary goal was to investigate if operating room time can be saved when not using IOPTH monitoring. Design: A retrospective analysis of patients who underwent parathyroidectomy for PHPT for a single adenoma between 2004-2019 was performed. Cure rates and operating room time were compared. Results: 423 patients were included. IOPTH was used in 248 patients (59%). Four patients were not cured, two from each group, with no significant difference between the groups (98.8% vs. 99.1%, p=0.725). Surgery time was significantly longer in the IOPTH group, p<0.001. Conclusions: There is no advantage for using IOPTH during parathyroidectomy in suitable clinical setting. A focused procedure may be safely performed without IOPTH while achieving non-inferior success rates and reducing operative time.

Mixed sexually transmitted infections in infertile couples: empirical treatment and influence on semen quality

Background: Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) and Ureaplasma urealyticum (UU) are common sexually transmitted infections (STIs) that are diagnosed in infertile couples (cps). In cases with their simultaneous presence in a patient (mixed STI, MSTIs), treatment is complicated by the different sensitivity of microorganisms to antibacterial drugs. Moreover, in cases of complicated infections, the empirical treatment should be started before obtaining the results of drug susceptibilities. Objective: The objective of the current study is to find the effective and well-tolerated combination of drugs for the empirical antibacterial treatment of mixed STIs presented by TV, MG and UU in infertile couples. We also aimed to establish the influence of mixed STIs on semen quality. Method: Our prospective study included 154 infertile couples (308 patients) with confirmed symptomatic MSTIs in one of the couples caused by the simultaneous presence of TV, MG and UU. All couples were randomized on three groups for empirical treatment: Group 1 (n=49 cps, 98 pts) who were treated by initial prescribing of anti-trichomoniasis drug Secnidazole, 2.0 g po followed by Azythromycin 500 mg on day 1 continuing by 250 mg on days 2-7; Group 2 (n=52 cps, 104 pts: Secnidazole, 2.0 g po followed by Josamycin 1000 mg bid for 12 days); Group 3 (n=53 cps, 106 pts: Secnidazole, 2.0 g po followed by Moxifloxacin 400 mg once daily for 12 days). The endpoints were clinical and microbiological cure rates as well as the frequency of side-effects in analyzed groups. We determined the basic parameters of the spermogram and Deoxyribonucleic acid (DNA) fragmentation levels in 59 patients with MSTIs before and at the 3rd, 6th and 9th month after pathogens eradication comparing them with results in 63 healthy sperm donors. Result: After the treatment, clinical cure rates in analyzed groups were 82.6% (Group 1) vs 96.1% (Group 2) vs 92.3% (Group 3). Microbiological cure rates (UU+MG) were 73.9 % vs 97.1 % vs 84.5% correspondingly (p<0.05). TV microbiological cure rates were 97.8% vs 98.0% vs 96.1% (p>0.05). Side-effects were registered in 28.6% vs 12.5% vs 18.9% cases correspondingly (p<0.05). In MSTIs patients, we registered the increasing DNA fragmentation rates, leucocytes count and decreasing semen volume, motility, vitality, sperm concentration, total spermatozoa number and number of spermatozoa with normal morphology. At the 6th month after complete pathogens eradication, these parameters approached normal values. Conclusion: At the present time, the combination of Secnidazole+Josamycin can be considered the most effective and well-tolerated for the empirical treatment in patients with MSTIs presented by TV, MG and UU. Complete eradication of these MSTIs in males improves their semen parameters.

Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments

HER2 positive breast cancer represent about 20% of all breast cancer subtypes and it was considered the subtype with the worst prognosis until the discovery of therapies directed against the HER2 protein. The determination of the status of the HER2 must be very precise and well managed to identify this subtype, and there are very specific and updated guides that allow its characterization to be adjusted. Treatment in local disease has been considerably improved with less aggressive and highly effective approaches and very high cure rates. In metastatic disease, average median survival rates of 5 years have been achieved. New highly active molecules have also been discovered that allow disease control in very complicated situations. This article reviews all these options that can be used for the management of this disease.

Effects of Parathyroidectomy on Normocalcemic Primary Hyperparathyroidism and the Role of Intraoperative PTH Measurement

Background Normocalcemic primary hyperparathyroidism (NCpHPT) and normohormonal primary hyperparathyroidism (NHpHPT) are recently recognized variants of primary hyperparathyroidism. Current guidelines for the management hyperparathyroidism recognize NCpHPT as one of the areas that are recommended for more research due to limited available data. Methods A retrospective review of patients who had parathyroidectomy between 2014 and 2019. We excluded patients with multiple endocrine neoplasia syndromes and secondary and tertiary hyperparathyroidism. Included patients were classified based on the biochemical profile into classic or normocalcemic hyperparathyroidism group. Collected data included demographics, preoperative localizing imaging, intraoperative parathyroid hormone levels, and postoperative cure rates. Results 261 patients were included: 160 patients in the classic and 101 patients in the normocalcemic group. Patients in the normocalcemic group had significantly more negative sestamibi scans (n = 58 [8.2%] vs 78 [51.3%], P = <.01), smaller parathyroid glands (mean weight 436.0 ± 593.0 vs 742.4 ± 1109.0 mg, P = .02), higher parathyroid hyperplasia rates (n = 51 [50.5%] vs 69 [43.1%]), and significantly higher intraoperative parathyroid hormone at 10 minutes (78.1 ± 194.6 vs 43.9 ± 62.4 1, P = .04). Positive predictive value of both intraoperative parathyroid hormone and cure rate was lower in the normocalcemic group (84.2% vs 95.7%) and (80.5% vs 95%), respectively. Conclusion Normocalcemic hyperparathyroidism is a challenging disease. Surgeons should be aware of the lower cure rate in this group, interpret intraoperative parathyroid hormone with caution, and have a lower threshold for bilateral neck exploration and 4 glands visualization.