Minimally invasive resection of heart valve papillary fibroelastoma: two case reports and review of the literature.

BACKGROUND: Cardiac papillary fibroelastomas are rare, accounting for approximately 10% of all cardiac tumors, with 44% of cases located on the aortic valve and only 15% of cases located on the tricuspid valve. However, the optimal management of papillary fibroelastomas remains varied. CASE PRESENTATION: We present two successful instances of treating heart valve papillary fibroelastomas through minimally invasive surgery. These cases involved heart valve papillary fibroelastomas located in two common sites: the aortic valve on the left heart, which was accessed via an upper hemi-sternotomy, and the tricuspid valve on the right heart, which was accessed via beating heart total thoracoscopy. CONCLUSION: The article consistently demonstrates the effectiveness of a minimally invasive surgical approach in managing heart valve papillary fibroelastomas. This study provides further evidence by presenting two cases of heart valve papillary fibroelastomas - one on the aortic valve and the other on the tricuspid valve - that were successfully treated using this approach, resulting in favorable outcomes.

Effects of gel volume on pharmacokinetics for vaginal and rectal applications of combination DuoGel-IQB4012, a dual chamber-dual drug HIV microbicide gel, in pigtailed macaques.

This study evaluated effects of differing gel volumes on pharmacokinetics (PK). IQB4012, a gel containing the non-nucleoside reverse transcriptase inhibitor IQP-0528 and tenofovir (TFV), was applied to the pigtailed macaque vagina and rectum. Vaginal gel volumes (1% loading of both drugs) were 0.5 or 1.5 ml; following wash-out, 1 or 4 ml of gel were then applied rectally. Blood, vaginal, and rectal fluids were collected at 0, 2, 4, and 24 h. Vaginal and rectal tissue biopsies were collected at 4 and 24 h. There were no statistically significant differences in concentrations for either drug between gel volumes within compartments at matched time points. After vaginal gel application, median IQP-0528 concentrations were ~ 104-105 ng/g, 105-106 ng/ml, and 103-105 ng/ml in vaginal tissues, vaginal fluids, and rectal fluids, respectively (over 24 h). Median vaginal TFV concentrations were 1-2 logs lower than IQP-0528 levels at matched time points. After rectal gel application, median IQP-0528 and TFV concentrations in rectal fluids were ~ 103-105 ng/ml and ~ 102-103 ng/ml, respectively. Concentrations of both drugs sampled in rectal tissues were low (~ 101-103 ng/g). For 1 ml gel, half of sampled rectal tissues had undetectable concentrations of either drug, and over half of sampled rectal fluids had undetectable TFV concentrations. These results indicate differences in drug delivery between the vaginal and rectal compartments, and that smaller vaginal gel volumes may not significantly compromise microbicide PK and prophylactic potential. However, effects of rectal gel volume on PK for both drugs were less definitive.

Imaging of subclinical haemopoiesis after stem-cell transplantation in patients with haematological malignancies: a prospective pilot study.

BACKGROUND: Haemopoietic stem-cell transplantation (HSCT) eradicates host haemopoiesis before venous infusion of haemopoietic stem cells (HSCs). The pathway to cellular recovery has been difficult to study in human beings because of risks associated with interventions during aplasia. We investigated whether 18F-fluorothymidine (18F-FLT) imaging was safe during allogenic HSCT and allowed visualisation of early cellular proliferation and detection of patterns of cellular engraftment after HSCT. METHODS: Eligible patients were aged 18-55 years, had high-risk haematological malignancies. All patients underwent myeloablation followed by HSCT. The imaging primary endpoint was detection of early subclinical engraftment after HSCT with 18F-FLT PET or CT. Imaging was done 1 day before and 5 or 9, and 28 days, and 1 year after HSCT. This study is registered with ClinicalTrials.gov, number NCT01338987. FINDINGS: Between April 1, 2014, and Dec 31, 2015, 23 patients were enrolled and assessable for toxic effects after completing accrual. 18F-FLT was not associated with any adverse events or delayed engraftment. 18F-FLT imaging objectively identified subclinical bone-marrow recovery within 5 days of HSC infusion, which was up to 20 days before engraftment became clinically evident. Quantitatively, 18F-FLT intensity differed significantly between myeloablative infusion before HSCT and subclinical HSC recovery (p=0·00031). 18F-FLT biodistribution over time revealed a previously unknown path of cellular recovery of haemopoiesis in vivo that mirrored fetal ontogeny. INTERPRETATION: 18F-FLT allowed quantification and tracking of subclinical bone-marrow repopulation in human beings and revealed new insights into the biology of HSC recovery after HSCT. FUNDING: National Institutes of Health, Ben's Run/Ben's Gift, Albert and Elizabeth Tucker Foundation, Mex Frates Leukemia Fund, Jones Family fund, and Oklahoma Center for Adult Stem Cell Research.

Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIVSF162p3 viral kinetics and tenofovir pharmacokinetics when delivered via intravaginal rings.

BACKGROUND: Intravaginal rings (IVR) for HIV prevention will likely be used by women on depot medroxyprogesterone acetate (DMPA) hormonal contraception. We used pigtailed macaques to evaluate the effects of DMPA on tenofovir disoproxil fumarate (TDF) IVR pharmacokinetics and viral shedding. METHODS: Mucosal tenofovir (TFV) levels were compared in SHIVSF162p3 -negative DMPA-treated (n=4) and normally cycling (n=6) macaques receiving TDF IVRs. Plasma viremia and vaginal shedding were determined in groups of SHIVSF162p3 -positive DMPA-treated (n=6) and normally cycling (n=5) macaques. RESULTS: Similar median vaginal fluid TFV concentrations were observed in the DMPA-treated and cycling macaques over 4 weeks (1.2×105 and 1.1.×105  ng/mL, respectively). Median plasma viremia and vaginal shedding AUC of the DMPA-treated (2.73×107 and 8.15×104 copies/mL, respectively) and cycling macaques (3.98×107 and 1.47×103 copies/mL, respectively) were statistically similar. CONCLUSIONS: DMPA does not affect TDF IVR pharmacokinetics or SHIV shedding.

Topical Delivery of Tenofovir Disoproxil Fumarate and Emtricitabine from Pod-Intravaginal Rings Protects Macaques from Multiple SHIV Exposures.

Topical preexposure prophylaxis (PrEP) against HIV has been marginally successful in recent clinical trials with low adherence rates being a primary factor for failure. Controlled, sustained release of antiretroviral (ARV) drugs may help overcome these low adherence rates if the product is protective for extended periods of time. The oral combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is currently the only FDA-approved ARV drug for HIV PrEP. A novel pod-intravaginal ring (IVR) delivering TDF and FTC at independently controlled rates was evaluated for efficacy at preventing SHIV162p3 infection in a rigorous, repeat low-dose vaginal exposure model using normally cycling female pigtailed macaques. Six macaques received pod-IVRs containing TDF (65 mg) and FTC (68 mg) every two weeks, and weekly vaginal exposures to 50 TCID50 of SHIV162p3 began one week after the first pod-IVR insertion. All pod-IVR-treated macaques were fully protected throughout the study (P = 0.0002, Log-rank test), whereas all control animals became infected with a median of 4 exposures to infection. The topical, sustained release of TDF and FTC from the pod-IVR maintained protective drug levels in macaques over four months of virus exposures. This novel and versatile delivery system has the capacity to deliver and maintain protective levels of multiple drugs and the protection observed here warrants clinical evaluation of this pod-IVR design.

Tenofovir disoproxil fumarate intravaginal ring protects high-dose depot medroxyprogesterone acetate-treated macaques from multiple SHIV exposures.

Preclinical HIV prevention models use either a single high-dose viral challenge in depot medroxyprogesterone acetate-treated macaques or repeated viral challenges in cycling macaques. We tested the efficacy of an intravaginal tenofovir disoproxil fumarate (TDF) ring in a model combining repeated 30-mg injections of depot medroxyprogesterone acetate every 6 weeks with vaginal viral challenges weekly for 12 weeks. Twelve macaques were randomized to TDF or placebo rings. All placebo macaques became infected after a median of 2 exposures, whereas only 1 TDF macaque became infected at the eighth exposure (P = 0.0012). The TDF ring provides durable protection in a stringent challenge model.

Pharmacokinetics and preliminary safety study of pod-intravaginal rings delivering antiretroviral combinations for HIV prophylaxis in a macaque model.

Preexposure prophylaxis using oral regimens involving the HIV nucleoside reverse transcriptase inhibitors tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) demonstrated efficacy in three clinical trials. Adherence was determined to be a key parameter for success. Incorporation of the TDF-FTC combination into intravaginal rings (IVRs) for sustained mucosal delivery could increase product adherence and efficacy compared with those of oral and vaginal gel formulations. A novel pod-IVR technology capable of delivering multiple drugs is described; this constitutes the first report of an IVR delivering TDF and FTC, as well as a triple-combination IVR delivering TDF, FTC, and the entry inhibitor maraviroc (MVC). The pharmacokinetics and preliminary local safety of the two combination pod-IVRs were evaluated in the pig-tailed macaque model. The devices exhibited sustained release at controlled rates over the 28-day study period. Median steady-state drug levels in vaginal tissues in the TDF-FTC group were 30 µg g(-1) (tenofovir [TFV], in vivo hydrolysis product of TDF) and 500 µg g(-1) (FTC) and in the TDF-FTC-MVC group were 10 µg g(-1) (TFV), 150 µg g(-1) (FTC), and 20 µg g(-1) (MVC). No adverse events were observed, and there were no toxicological findings. Mild-to-moderate increases in inflammatory infiltrates were observed in the vaginal tissues of some animals in both the presence and the absence of the IVRs. The IVRs did not disturb the vaginal microbiota, and levels of proinflammatory cytokines remained stable throughout the study. Pod-IVR candidates based on the TDF-FTC combination have potential for the prevention of vaginal HIV acquisition and merit clinical investigation.

Intravaginal ring eluting tenofovir disoproxil fumarate completely protects macaques from multiple vaginal simian-HIV challenges.

Topical preexposure prophylaxis interrupts HIV transmission at the site of mucosal exposure. Intermittently dosed vaginal gels containing the HIV-1 reverse transcriptase inhibitor tenofovir protected pigtailed macaques depending on the timing of viral challenge relative to gel application. However, modest or no protection was observed in clinical trials. Intravaginal rings (IVRs) may improve efficacy by providing long-term sustained drug delivery leading to constant mucosal antiretroviral concentrations and enhancing adherence. Although a few IVRs have entered the clinical pipeline, 100% efficacy in a repeated macaque vaginal challenge model has not been achieved. Here we describe a reservoir IVR technology that delivers the tenofovir prodrug tenofovir disoproxil fumarate (TDF) continuously over 28 d. With four monthly ring changes in this repeated challenge model, TDF IVRs generated reproducible and protective drug levels. All TDF IVR-treated macaques (n = 6) remained seronegative and simian-HIV RNA negative after 16 weekly vaginal exposures to 50 tissue culture infectious dose SHIV162p3. In contrast, 11/12 control macaques became infected, with a median of four exposures assuming an eclipse of 7 d from infection to virus RNA detection. Protection was associated with tenofovir levels in vaginal fluid [mean 1.8 × 10(5) ng/mL (range 1.1 × 10(4) to 6.6 × 10(5) ng/mL)] and ex vivo antiviral activity of cervicovaginal lavage samples. These observations support further advancement of TDF IVRs as well as the concept that extended duration drug delivery devices delivering topical antiretrovirals could be effective tools in preventing the sexual transmission of HIV in humans.

Autoimmune pancreatitis in an Asian-dominant American population.

Autoimmune pancreatitis is a rare type of chronic pancreatitis that occurs predominantly in males and was first described in the Asian population. The following study seeks to characterize autoimmune pancreatitis in Hawai'i's Asian-dominant population through a retrospective review of 65 pancreaticoduodenectomy cases performed between 2000 and 2010. Three of the 65 pancreaticoduodenectomies were diagnosed with autoimmune pancreatitis, and 3 additional cases were diagnosed prior to surgery. All six patients were males and presented with obstructive jaundice, 5 with weight loss, and 4 with epigastric pain and elevated serum lipase. All six patients showed elevated serum IgG4. Imaging revealed findings typical of pancreatic malignancy: distal bile duct stricture and pancreatic head mass. However, no nodal involvement and vascular invasion were found. In conclusion, autoimmune pancreatitis should be considered in patients presenting with obstructive jaundice. Elevated serum IgG4, normal serum carbohydrate antigen CA19-9, a benign fine needle aspiration/core biopsy, and a therapeutic response to corticosteroid are typical findings of autoimmune pancreatitis. Serum IgG4 measurement is a useful tool to help differentiate autoimmune pancreatitis from most pancreatic cancers. It is important to consider autoimmune pancreatitis as a differential diagnosis of pancreatic malignancy to avoid unnecessary surgery.

Lidocaine spray and outpatient hysteroscopy: randomized placebo-controlled trial.

OBJECTIVE: To assess the efficacy of lidocaine spray during outpatient hysteroscopy for reducing procedure-related pain and to identify risk factors for discomfort. METHODS: One hundred twenty-one women were assigned randomly to have application of lidocaine spray or placebo to the uterine cervix during outpatient hysteroscopy. The main outcome measure was pain during hysteroscopy, assessed on a visual analog scale. RESULTS: There was no statistically significant difference between study and control groups in mean age, rate of nulliparity, postmenopausal state, need for cervical dilation, or percentage of women who used hormone replacement therapy. Indications for diagnostic hysteroscopy were similar between groups. Women in the lidocaine group had statistically significantly less pain during the procedure than women in the placebo group (2.2 +/- 1.9 and 3.7 +/- 2.5, respectively; P <.001). Women with abnormal uterine findings (submucous myoma, endometrial polyps, or intrauterine adhesions) had significantly higher pain scores than women with normal cavities (2.2 +/- 1.9 and 3.2 +/- 2.4, respectively; P <.002). Aerosol anesthesia and normal uterine findings were independently associated with less pain. No procedure had to be abandoned because of excessive pain or complications, and no women required hospitalization. CONCLUSION: Women treated with lidocaine spray had significantly less pain. Uterine cavity abnormality might be associated with a higher degree of pain during hysteroscopy.

Vietnam and activities of community-based rehabilitation.

This paper describes the development of, and current situation regarding, community-based rehabilitation (CBR) in Vietnam. Vietnam is one of the few countries to universally adopt CBR as a means of delivering effective rehabilitation to its citizens. Some information regarding the demography of the country is presented. The administrative structure associated with rehabilitation delivery and the prevalence of disability in the country are also discussed. Finally, the strengths, weaknesses and constraints of CBR are discussed.

[Mechanical and metabolic complications of hysteroscopic surgery: report of a retrospective study of 352 procedures]. / Complications mécaniques et métaboliques de l'hystéroscopie opératoire: à propos d'une étude rétrospective de 352 interventions.

Our objective was to determine, in a retrospective study of 352 operative hysteroscopies: (a) the rates and the types of complications and (b) the risk factors of peroperative perforations. The most important complications represented 1.7% including two haemorrhage, one symptomatic metabolic abnormalities and three uterine perforations with bowel injuries (0.8%). Furthermore, minor complications were observed in 9.3% including non symptomatic metabolic abnormalities (5.5%) and uterine perforations without visceral injury. Among mechanical complications, the majority were uterine perforations (4%). No relation was found between menopausal status of the patients and the occurrence of uterine perforation. In contrast, the perforation rate was statistically greater in patients treated for synechia than those found for myoma (p < 0.0001). Furthermore, the perforation rate was statistically higher for resection of myomas as compared with endometrial resection (p < 0.0001) or polyp resection (p < 0.0008). Moreover, in our experience, the perforation rate depended on hysteroscopic experience of surgical operators.