Ibrutinib-associated cutaneous mucormycosis due to an Apophysomyces species: report of a case and review of the literature.

The use of ibrutinib, a Bruton tyrosine kinase inhibitor, has been associated with invasive fungal infections (IFIs). We describe a case of Apophysomyces infection associated with long-term use of ibrutinib for the treatment of chronic lymphocytic leukemia as well as perform a literature review of Mucormycosis infections in patients on ibrutinib. Our review found that the onset of IFI can occur within months to years of starting tyrosine kinase inhibitors. These reports provide a more complete picture of the risk of IFI while patients are on ibrutinib. Our case also demonstrates the utility of molecular techniques in the diagnosis of IFI, as the diagnosis was made using 28S rDNA/internal transcribed spacer PCR.

Multiple factors are involved in regulation of extracellular membrane vesicle biogenesis in Streptococcus mutans.

Streptococcus mutans, a major etiological agent of human dental caries, produces membrane vesicles (MVs) that contain protein and extracellular DNA. In this study, functional genomics, along with in vitro biofilm models, was used to identify factors that regulate MV biogenesis. Our results showed that when added to growth medium, MVs significantly enhanced biofilm formation by S. mutans, especially during growth in sucrose. This effect occurred in the presence and absence of added human saliva. Functional genomics revealed several genes, including sfp, which have a major effect on S. mutans MVs. In Bacillus sp. sfp encodes a 4'-phosphopantetheinyl transferase that contributes to surfactin biosynthesis and impacts vesiculogenesis. In S. mutans, sfp resides within the TnSmu2 Genomic Island that supports pigment production associated with oxidative stress tolerance. Compared to the UA159 parent, the Δsfp mutant, TW406, demonstrated a 1.74-fold (p < .05) higher MV yield as measured by BCA protein assay. This mutant also displayed increased susceptibility to low pH and oxidative stressors, as demonstrated by acid killing and hydrogen peroxide challenge assays. Deficiency of bacA, a putative surfactin synthetase homolog within TnSmu2, and especially dac and pdeA that encode a di-adenylyl cyclase and a phosphodiesterase, respectively, also significantly increased MV yield (p < .05). However, elimination of bacA2, a bacitracin synthetase homolog, resulted in a >1.5-fold (p < .05) reduction of MV yield. These results demonstrate that S. mutans MV properties are regulated by genes within and outside of the TnSmu2 island, and that as a major particulate component of the biofilm matrix, MVs significantly influence biofilm formation.

TP53 Gain-of-Function Mutations in Circulating Tumor DNA in Men With Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Circulating tumor DNA (ctDNA), which can be assessed by liquid biopsy, can provide valuable genomic information that may affect treatment response in prostate cancer. The aim of this study was to characterize TP53 mutations and treatment history in prostate cancer. PATIENTS AND METHODS: This study included 143 patients with metastatic castration-resistant prostate cancer who had undergone ctDNA sequencing via Guardant360 testing. The presence or absence of TP53 mutations was analyzed along with treatment history for this group. TP53 mutations were further classified as gain of function (GOF) or not GOF, and analyzed with prior therapies. RESULTS: Chi-square analysis was performed for treatment history and TP53 status (further specified as all TP53 mutations or only TP53 GOF mutations). There were no associations between prior receipt of abiraterone/enzalutamide therapy and all TP53 mutations, or between docetaxel therapy and all TP53 mutations. However, TP53 GOF mutations had a positive association with prior abiraterone/enzalutamide therapy (P = .047). There was no association of TP53 GOF mutations with prior docetaxel therapy. The most frequent alterations co-occurring with all TP53 mutations were in AR, BRAF, EGFR, MYC, and PIK3CA. Common coalterations with TP53 GOF mutations included AR, BRAF, EGFR, RB1, NF1, and PIK3CA. There was an association of RB1 mutations with TP53 GOF mutations, versus RB1 mutations and no TP53 GOF mutations (P = .0036). CONCLUSION: TP53 GOF mutations may provide a valuable pathway to delineate metastatic castration-resistant prostate cancer TP53 mutations into therapeutic categories. Association with disease progression while receiving abiraterone/enzalutamide therapy was apparent in this study; however, further studies are needed to elaborate the therapeutic and prognostic implications.

The mini-resectoscope: a new instrument for office hysteroscopic surgery.

BACKGROUND: Outpatient hysteroscopy has become well-established for the investigation abnormal uterine bleeding. Although "See and Treat" clinics have been widely introduced, the types of procedures offered are limited, and many patients with intrauterine pathology continue to be admitted as in-patients for hysteroscopic surgery. We wanted to investigate the feasibility and acceptability of surgery for small intrauterine lesions without the need for general anesthesia by using a miniature resectoscope. METHODS: This was a prospective observational study on 30 women with abnormal uterine bleeding associated with endometrial polyps or small (<3 cm) type 0 or 1 submucous fibroids. Hysteroscopic polypectomy (n=26) or myomectomy (n=4) was carried out using a 16 Fr gauge mini-resectoscope. RESULTS: Ten procedures were carried out in the outpatient clinic and 20 in the operating theatre. Sixteen procedures were done without any anaesthesia and 14 after intra-cervical local anesthetic injections. The polyps and fibroids ranged in size from 1 to 5 cm, and all procedures took less than 15 minutes from the time the vagina was instrumented to the end of surgery. All procedures were completed successfully and were well tolerated with little discomfort. There were no complications. CONCLUSIONS: The mini-resectoscope appears to be an efficient and acceptable instrument for hysteroscopic surgery and can be used without general anesthesia for minor procedure such as polypectomy and the resection of small submucous fibroids.

Female sterilization.

There has been considerable development and implementation of new contraceptive methods over the last 15 years. However, sterilization has remained the most widely used method around the world. Ideally, the procedure should be safe, have a high efficacy, be readily accessible, and be personally and culturally acceptable. The cost for each procedure would be low and the method would be simple, quick, easily learned and be able to be performed in an outpatient setting without general anesthesia. A transuterine method of female sterilization has long been the ideal for the gynecologist. The Essure system fulfils many of the criteria, and is the first one to be approved by the US FDA. However, there is still a need for further research to find a device with the success rate of the Essure but without its irreversibility.

Do patients want to see recordings of their surgery?

OBJECTIVE: In an effort to improve patients' understanding and perception of their surgery and communication between doctors and patients we have evaluated the use of a mobile digital video recorder in the case of women undergoing gynaecological surgery. STUDY DESIGN: Patients scheduled for endoscopic or open surgery were asked if they would allow their surgery be recorded on a dedicated computer system. Those who agreed were offered the opportunity to have real-time edited highlights of their surgery recorded simultaneously on a miniature digital video recorder. They were shown the edited recording before discharge from hospital, and their reaction was assessed using a structured questionnaire. RESULTS: 51/54 (94.4%) women agreed to their surgery being recorded on the computer system, and 37/54 (68.5%) asked to see the edited highlights. The median duration of the computer and portable recordings for the 37 patients was 90 min (range 2-280) and 3.3 min (range 1-13.6) respectively. Thirty-four (91.9%) reported that the edited recording gave them a better understanding of their medical condition and surgery. Thirty (81.1%) would have liked a copy of the recording. CONCLUSIONS: Portable video recorders are a convenient tool for recording surgical procedures. In our experience, about two-third of patients are interested in reviewing their surgery and find it provides useful information and a perceived better understanding of their condition. As these recording devices are small and fit into a pocket, their use could easily become a routine part of post-operative ward rounds. For the surgeon, such recordings have an educational value and provide the basis for a library of surgery as well as being useful when planning future management or for referral purposes.

A new technique for temporary ovarian suspension: temporarily displacing the ovaries anterior to the uterus facilitates pelvic side wall access in the laparoscopic treatment of endometriosis.

The adnexa frequently hinder access to the pelvic side wall during laparoscopic surgery for endometriosis. An innovative tactic can facilitate dissection.

Where is the aorta? Is it worth palpating the aorta prior to laparoscopy?

BACKGROUND: Injury to major retroperitoneal vessels is the most catastrophic complication of laparoscopy. Knowledge of the site of the aortic bifurcation prior to inserting the umbilical port would be expected to reduce the risk of this type of injury. The aim of the study is to determine the feasibility of identifying the aortic bifurcation by palpation prior to the operation. METHODS: We studied 100 patients undergoing laparoscopic surgery or laparotomy. After prepping and draping, the operating surgeon felt for the aortic bifurcation to determine its position in relation to the umbilicus. We then related our findings to the height, weight, and body mass index of the patient. RESULTS: The aorta could not be palpated in 15% of cases, including almost 2/3 of women who were obese (body mass index >30). In the remaining 85% cases, where the aorta was palpable, the bifurcation was above the level of the umbilicus in 30 (35%) cases, at the umbilicus in 45 (53%) cases, and below in 10 (12%) cases. We did not find any significant effect of body mass index, height, or weight on the level of the aortic bifurcation by palpation. No vascular injury occurred in the laparoscopic cases during the study. CONCLUSIONS: The aortic bifurcation is palpable in the majority of women undergoing surgery, including 93% of those with a low or normal body mass index who are at higher risk of vascular injury. We recommend the routine palpation for the aortic bifurcation as a simple means to reduce the risk of injury to a major retroperitoneal vessel.

Surgical and radiological management of uterine fibroids in the UK.

PURPOSE OF REVIEW: Uterine fibroids remain the most common benign gynaecological pathology and a frequent reason for gynaecological referral and treatment. The range of available treatments is currently undergoing a minor revolution with the introduction of nonsurgical therapies, but their role remains to be established. RECENT FINDINGS: Arguably the most significant change in recent years has been the availability of uterine artery embolization as a form of nonsurgical management. A survey of UK gynaecologists, however, has shown that the option of embolization is only utilized by just over half the respondents. Instead, conventional surgery such as hysterectomy and myomectomy remain the mainstay of nonsymptomatic treatment. In the absence of gross uterine enlargement, vaginal hysterectomy is feasible and safe. Fewer hysterectomies, however, are being done and more women are undergoing myomectomy, with almost 50% of UK consultant gynaecologists carrying out hysteroscopic myomectomy and just over 10% laparoscopic myomectomy. SUMMARY: Greater utilization of less invasive endoscopic or vaginal procedures for the management of uterine fibroids seems a reasonable target. In the longer term, it is likely that the various nonsurgical techniques which shrink fibroids and thereby reduce symptoms will have an increasingly important role in the treatment of this common condition.

Is inferior dissection of the rectus sheath necessary during Pfannenstiel incision for lower segment Caesarean section? A randomised controlled trial.

OBJECTIVE: The objective was to determine the benefit of non-dissection of the rectus sheath inferiorly in a Pfannenstiel incision during an elective Caesarean section with regard to operative blood loss and post-operative pain. DESIGN: A randomised controlled trial. SETTING: The Royal Free Teaching Hospital in London. POPULATION: One hundred and twenty women who underwent elective Caesarean section delivery. METHOD: Women were randomised to have dissection or non-dissection of the rectus sheath inferiorly during an elective Caesarean section. MAIN OUTCOME MEASURES: Estimated blood loss during the operation, as well as the difference between pre- and post-operative haemoglobin levels. Post-operative pain was assessed by the visual analogue scale, a verbal rating scale and the use of post-operative analgesia. Patient satisfaction was assessed by a verbal rating scale. RESULTS: There was no significant difference in the estimated blood loss during the procedure between the two groups; however, the mean difference between the pre-operative and post-operative haemoglobin was significantly smaller in the study group (p=0.05). There was a statistically significant difference in both the visual analogue scale (p-value=0.03) and the verbal rating scale scores (p-value=0.02) for pain between the two groups, with lower scores for the study group. There was no overall difference in the verbal rating scale scores for patient satisfaction. CONCLUSION: Non-dissection of the rectus sheath inferiorly in Pfannenstiel incisions during Caesarean section procedures is associated with a significant reduction in the post-operative pain as well as a smaller drop in post-operative haemoglobin.

Currently available devices for female sterilization.

Sterilization is now the method of family planning most commonly used in the world. Over the last 150 years, research has evolved in the search for the ideal method of female sterilization. The procedure should ideally have high efficacy, be readily accessible and be personally and culturally acceptable. The method should be simple, quick, easily learned and be able to be performed in an outpatient setting without general anesthesia. The most common and effective method for sterilization has, thus far, been via the laparoscopic route. Hysteroscopic sterilization, however, potentially fulfills many of these ideal criteria, but until recently has remained more of a concept than a reality.

Digital recording of surgical procedures using a personal computer.

OBJECTIVE: To develop a system for recording surgical procedure digitally using a personal computer with real-time compression of the video signal. STUDY DESIGN: We built the system around a modern personal computer with a large hard disk to allow recording of over 250 h of continuous surgery. Digital capture from the camera was achieved using a standard external analogue-digital converter linked to the computer via a firewire cable. The software for capturing, compressing and editing movie files were obtained free of charge from the internet. The optimal settings for the software was determined. RESULTS: We have successfully used this system to record over 100 major and minor hysteroscopic, laparoscopic, vaginal and open gynaecological. Despite compression, the quality of the movies was judged to be very good and still images excellent. The recordings could be integrated in to standard presentation. Still pictures could be printed to provide hard copies for patients and medical notes, and movies burnt on to CDs or DVDs. CONCLUSIONS: A digital recording system built around a standard personal computer is relatively cheap, versatile and has a huge capacity to record surgical procedures.

Hysteroscopic tubal sterilization.

This article provides an overview of the history of hysteroscopic sterilization including the current state of the art and future ideals. Unlike laparoscopic techniques, sterilization by hysteroscopy can be performed in an outpatient setting without general anesthesia. Many attempts have been made to develop a safe and effective method, but until recently, without success. The Essure system is the first one that seems to be a realistic alternative to laparoscopic sterilization, but is irreversible. The search is still on for the optimum method of hysteroscopic sterilization.