Suppressive Therapy Research Articles

CD4 dim CD8 bright T cells are inversely associated with neuro-inflammatory markers among people with HIV.

HIV-associated neuroinflammation persists in the brain despite suppressive combination antiretroviral therapy (cART). We evaluated associations between a subset of CD8 + T cells, termed CD4 dim CD8 bright T cells, and soluble markers of immune activation and/or neuroinflammation in the cerebrospinal fluid (CSF) and plasma of people with HIV (PWH). Fifteen cART-naive PWH were enrolled and underwent blood draw, lumbar puncture for CSF collection, and neuropsychological tests at week 0 (pre-cART) and 24 weeks after cART initiation. CSF and peripheral blood T cells were evaluated with flow cytometry and soluble markers of immune activation were measured by multiplex and singleplex assays. Spearman bootstrap correlation coefficients with 10 000 resamples were computed and reported with corresponding 95% confidence intervals (CIs) for each marker of interest and T-cell type. The frequency of CSF CD4 dim CD8 bright T cells at week 0 was inversely related with CSF neopterin. In contrast, at week 24, CSF CD4 - CD8 + T cells were positively correlated with CSF s100β, a marker of brain injury. In the blood, at week 0, CD4 dim CD8 bright T cells were inversely correlated with MCP-1, IP-10, IL-8, IL-6, G-CSF, and APRIL and positively correlated with plasma RANTES and MMP1. At week 0, the frequency of blood CD4 - CD8 + were positively correlated with CRP and BAFF. CD4 dim CD8 bright T cells are associated with some anti-inflammatory properties, whereas CD4 - CD8 + T cells may contribute to inflammation and injury. Assessing the contrast between these two cell populations in neuroHIV may inform targeted therapeutic intervention to reduce neuroinflammation and associated neurocognitive impairment.

Metastatic Malignant Struma Ovarii in a Nulliparous Patient: A Case Report

Introduction: Malignant struma ovarii is a rare tumor, Due its rarity treatments and follow-up approaches are not clearly standardized. Case Presentation: we present a case of a 29 -year-old, nulliparous woman with metastatic malignant struma ovarii revealed by abnormal vaginal bleeding and abdominal-pelvic pain. After surgical resection, the patient had complementary radioiodine therapy (131I) after total thyroidectomy. She received a treatment dose of 100 mCi of 131I followed by post-therapy whole-body scintigraphy. Discussion: Histological diagnosis of malignant struma ovarii is similar to that of well differentiated thyroid carcinoma. there are no guidelines regarding the management of this type of cancer. After surgical resection of malignant struma ovarii, adjuvant therapy with thyroidectomy followed by radioactive 131 I therapy and suppressive thyroxine therapy is suggested. The same follow-up as thyroid cancer is commonly adopted, with abdomino-pelvic evaluation. Conclusion: Large clinical studies are needed to standardize the care of patients with malignant struma ovarii.

Long-Term Outcomes Following Fairly Brief Androgen Suppression and Stereotactic Radiation Therapy in High-Risk Prostate Cancer: Update From the FASTR/FASTR-2 Trials

There is limited data on the long-term outcomes of ultrahypofractionated radiation therapy in high-risk prostate cancer. The FASTR and FASTR-2 trials were designed to assess the tolerability of stereotactic ablative radiation therapy (SABR) in this context. Herein, the long-term results are reported. Eligible patients had localized high-risk prostate cancer and were either ≥70 years old, had a score of ≥3 on the Vulnerable Elderly Scale, or declined standard therapy. Nineteen patients from a single institution were enrolled on FASTR between 2011 and 2015. They received 40 Gy to the prostate and 25 Gy to the pelvic lymph nodes in 5 weekly fractions, with 12 months of androgen deprivation therapy (ADT). Thirty patients from the same institution were enrolled on FASTR-2 between 2015 and 2017. They received 35 Gy to the prostate alone in 5 weekly fractions, with 18 months of ADT. Updated toxicity and outcomes were assessed retrospectively. Kaplan-Meier estimates were calculated for biochemical failure-free survival, freedom from distant metastases, prostate cancer-specific survival, and overall survival. Forty-four patients were eligible for analysis, 16 from FASTR and 28 from FASTR-2. Thirty-four patients (77%) were >70 years old. High-risk features included Gleason score ≥8 (n=20, 46%), T3-T4 disease (n=12, 27%), and baseline prostate-specific antigen > 20 (n=22, 50%). Median follow-up was 6.4 years. The 5-year cumulative incidence of late grade ≥3 genitourinary/gastrointestinal toxicity was 32% in FASTR and 11% in FASTR-2. At 5 years, the combined rates of biochemical failure-free survival, freedom from distant metastases, prostate cancer-specific survival, and overall survival were 72%, 90%, 92%, and 83%, respectively. SABR can be safely delivered in high-risk prostate cancer by optimizing technical delivery, particularly with adherence to strict dose constraints for organs at risk. The clinical outcomes in FASTR and FASTR-2 were largely comparable to more standard fractionation schemes plus ADT, but further modifications may improve disease control. Larger randomized trials are necessary to better understand the efficacy and tolerability of this approach.

H2S-Reactivating Antitumor Immune Response after Microwave Thermal Therapy for Long-Term Tumor Suppression.

Microwave thermal therapy (MWTT) is one of the most potent ablative treatments known, with advantages like deep penetration, minimal invasion, repeatable operation, and low interference from bone and gas. However, microwave (MW) is not selective against tumors, and residual tumors after incomplete ablation will generate immunosuppression, ultimately making tumors prone to recurrence and metastasis. Herein, a nano-immunomodulator (Bi-MOF-l-Cys@PEG@HA, BMCPH) is proposed to reverse the immunosuppression and reactivate the antitumor immune effect through responsively releasing H2S in tumor cells for improving MWTT. Under MW irradiation, BMCPH will mediate MWTT to ablate tumors and release l-cysteine (l-Cys) to react with the highly expressed cystathionine β-synthase in tumor to generate H2S. The generated H2S can inhibit the accumulation of myeloid-derived suppressor cells (MDSCs) and promote the expression of cytotoxic T lymphocytes (CTLs). Moreover, Bi-MOF can also scavenge reactive oxygen species (ROS), a major means of MDSCs-mediated immunosuppression, to further weaken the immunosuppressive effect. Simultaneously, the surface-covered HA will gather CTLs around the tumor to enhance the immune response. This nano gas immunomodulator provides an idea for the sensitive and tunable release of unstable gas molecules at tumor sites. The strategy of H2S gas to reverse immunosuppression and reactivate antitumor immune response introduces a direction to reduce the risk of tumor recurrence and metastasis after thermal ablation.

Estimating the contribution of CD4 T cell subset proliferation and differentiation to HIV persistence

Persistence of HIV in people living with HIV (PWH) on suppressive antiretroviral therapy (ART) has been linked to physiological mechanisms of CD4+ T cells. Here, in the same 37 male PWH on ART we measure longitudinal kinetics of HIV DNA and cell turnover rates in five CD4 cell subsets: naïve (TN), stem-cell- (TSCM), central- (TCM), transitional- (TTM), and effector-memory (TEM). HIV decreases in TTM and TEM but not in less-differentiated subsets. Cell turnover is ~10 times faster than HIV clearance in memory subsets, implying that cellular proliferation consistently creates HIV DNA. The optimal mathematical model for these integrated data sets posits HIV DNA also passages between CD4 cell subsets via cellular differentiation. Estimates are heterogeneous, but in an average participant’s year ~10 (in TN and TSCM) and ~104 (in TCM, TTM, TEM) proviruses are generated by proliferation while ~103 proviruses passage via cell differentiation (per million CD4). In simulations, therapies blocking proliferation and/or enhancing differentiation could reduce HIV DNA by 1-2 logs over 3 years. In summary, HIV exploits cellular proliferation and differentiation to persist during ART but clears faster in more proliferative/differentiated CD4 cell subsets and the same physiological mechanisms sustaining HIV might be temporarily modified to reduce it.

Long-Term Outcomes Following Fairly Brief Androgen Suppression and Stereotactic Radiation Therapy in High-Risk Prostate Cancer: Update from the FASTR/FASTR-2 Trials.

There has been emerging interest in the role of ultra-hypofractionated radiotherapy for high-risk prostate cancer, especially given its low α/β ratio. However, there is limited data on the long-term outcomes of this treatment strategy. The FASTR and FASTR-2 clinical trials were designed to assess the tolerability of stereotactic ablative body radiotherapy (SABR) in high-risk prostate cancer. FASTR was discontinued early due to unacceptable acute toxicity, whereas the acute toxicities in FASTR-2 were minimal. Herein, the long-term results from these trials are reported. Eligible patients had at least 1 high-risk feature as per the National Comprehensive Cancer Network criteria for high-risk prostate cancer, no evidence of metastatic disease, and either a score of 3+ on the Vulnerable Elderly Scale or declined standard therapy. A total of 19 patients from a single institution were enrolled on FASTR between 2011 and 2015. They received 40 Gy to the prostate and 25 Gy to the pelvic lymph nodes in 5 fractions delivered once weekly for 5 weeks, along with 1 year of androgen deprivation therapy (ADT). The excessive acute toxicity in FASTR prompted several modifications in FASTR-2, including the omission of nodal irradiation. A total of 30 patients from the same institution were enrolled on FASTR-2 between 2015 and 2017. They received 35 Gy to the prostate alone in 5 fractions delivered once weekly for 5 weeks, along with 18 months of ADT. A total of 44 patients were eligible for analysis, 16 from FASTR and 28 from FASTR-2. Most patients were >70 years old (77%). High-risk features included Gleason score ≥8 (46%), T3-T4 disease (27%) and baseline PSA >20 (50%). With a median follow-up of 6.4 years, the cumulative incidence of grade ≥3 genitourinary/gastrointestinal toxicity was 50% among FASTR patients and 7% among FASTR-2 patients. At 5 years, the combined rates of biochemical failure-free survival, freedom from distant metastases, prostate cancer-specific survival and overall survival were 72%, 90%, 92% and 83%, respectively. A total of 12 patients (27%) required further treatment. No significant differences in clinical outcomes were noted between the FASTR and FASTR-2 cohorts. SABR for high-risk prostate cancer is an attractive option for reducing treatment burden. Clinical outcomes and toxicity with the FASTR-2 protocol were comparable to conventionally-fractionated radiotherapy plus ADT. Larger prospective, randomized trials exploring the role of SABR with ADT in high-risk disease are necessary to better understand the efficacy and tolerability of this approach.

428 Discontinuation of inhaled antipseudomonal suppressive therapy in cystic fibrosis

428 Discontinuation of inhaled antipseudomonal suppressive therapy in cystic fibrosis

Subcentimetric papillary thyroid carcinoma with extensive lymph node and brain metastasis: case report and review of literature.

We report a 61-year-old male patient without personal history of thyroid carcinoma or radiation exposure. In 2011, he presented with a cervical mass whose biopsy diagnosed a papillary thyroid carcinoma (PTC) in a lymph node metastasis (LNM). Total thyroidectomy with lymphadenectomy of central and ipsilateral compartment was performed. Histopathology identified a 2 mm follicular variant of PTC and LNM in 25/25 lymph nodes. The patient was treated with 150 mCi of radioactive iodine (RAI), followed by levothyroxine suppressive therapy. In 2016, a retrotracheal mass was diagnosed, suggesting local recurrence; patient was submitted to surgical excision and RAI therapy (120 mCi). Due to seizures, in 2019, a brain CT was performed that diagnosed brain metastases. The patient underwent debulking of the main lesion. Histopathology analysis confirmed a metastatic lesion with variated morphology: classical PTC and follicular pattern and hobnail and tall cell features. Molecular analysis revealed BRAFV600E in LNM at presentation and BRAFV600E and TERT promoter (TERTp) mutations in the recurrent LNM and brain metastasis. Based upon this experience we review the reported cases of subcentimetric PTC with brain metastases and discuss the molecular progression of the present case. Papillary microcarcinoma (PMCs) usually have very good prognosis with low impact on patient survival. PMCs presenting in elderly patients with LNM at diagnosis may carry a guarded outcome. Brain metastasis although rare indicate aggressive phenotypic features. Patient risk stratification of PMCs based on histopathological analysis and genetic testing may have a significant impact on prognosis providing therapeutic markers, that may predict disease progression and overall outcome.

524 Acid suppression therapy and associations with growth, gut microbiome, and early-onset lung disease in young children with cystic fibrosis

524 Acid suppression therapy and associations with growth, gut microbiome, and early-onset lung disease in young children with cystic fibrosis

Should We Use Rifampicin in Periprosthetic Joint Infections Caused by Staphylococci When the Implant Has Been Exchanged? A Multicenter Observational Cohort Study.

Previous studies demonstrated the efficacy of a rifampicin-based regimen in the treatment of acute staphylococcal periprosthetic joint infections (PJIs) treated with surgical debridement. However, evidence is lacking to support the use of rifampicin in cases where the implant is exchanged during revision. We included all consecutive cases of staphylococcal PJIs treated from January 2013 to December 2018 with revision surgery in this international, retrospective, multicenter observational cohort study. PJI was defined according to the European Bone and Joint Infection Society diagnostic criteria. A relapse or reinfection during follow-up, the need for antibiotic suppressive therapy, the need for implant removal, and PJI-related death were defined as clinical failure. Cases without reimplantation or with follow-up <12 months were excluded. A total of 375 cases were included in the final analysis, including 124 1-stage exchanges (33.1%) and 251 2-stage exchanges (66.9%). Of those, 101 cases failed (26.9%). There was no statistically significant difference in failure of patients receiving rifampicin (22.5%, 42/187) and those not receiving rifampicin (31.4%, 59/188; P = .051). A subanalysis of chronic PJIs treated by 2-stage exchange arthroplasty demonstrated a lower failure rate in cases treated with rifampicin (15%) compared with the no-rifampicin group (35.5%; P = .005). In this subgroup, the use of rifampicin and an antibiotic holiday of >2 weeks were independent predictors of clinical success (odds ratio [OR], 0.36; 95% CI, 0.15-0.88; and OR, 0.19; 95% CI, 0.04-0.90; respectively). Combination treatment with rifampicin increases treatment success in patients with chronic staphylococcal PJI treated with 2-stage exchange arthroplasty.

Epilepsiechirurgie beim therapierefraktären Status epilepticus des Kindesalters

AbstractThe mainstay of status epilepticus (SE) treatment is pharmacotherapy with anti-seizure medications (ASM). In refractory status epilepticus (RSE), when additional ASM are not effective, high-dose suppressive therapy with either benzodiazepines, thiopental, phenobarbitone, or propofol is used to suppress clinical and EEG seizure activity. However, in selected eligible cases of RSE or in super-refractory cases, epilepsy surgery may be the treatment of choice to terminate SE. Here, we review epilepsy surgery including deep brain stimulation (DBS) for treatment for RSE with emphasis on special aspects of presurgical evaluation, patient selection, and outcome. We focus on surgical treatment options for patients in the acute phase of RSE, who have received high-dose suppressive therapy prior to surgery in the majority of the cases.

Randomised clinical trial: Efficacy and safety of on-demand vonoprazan versus placebo for non-erosive reflux disease.

Non-erosive reflux disease (NERD) symptoms are often episodic, making on-demand treatment an attractive treatment approach. We compared the efficacy and safety of on-demand vonoprazan versus placebo in patients with NERD. Patients with NERD, defined as heartburn for ≥6 months and for ≥4/7 consecutive days with normal endoscopy, received once-daily vonoprazan 20 mg during a 4-week run-in period. Patients without heartburn during the last 7 days and with ≥80% study drug and diary compliance were randomised 1:1:1:1 to vonoprazan 10, 20, 40 mg or placebo on-demand for 6 weeks. The primary endpoint was the percentage of evaluable heartburn episodes completely relieved within 3 h of on-demand dosing and sustained for 24 h. Of 458 patients in the run-in period, 207 entered the on-demand period. In the vonoprazan 10 mg group, 56.0% (201/359) of evaluable heartburn episodes met the criteria for complete and sustained relief; 60.6% (198/327) in the 20 mg group; and 70.0% (226/323) in the 40 mg group, compared with 27.3% (101/370) in the placebo group (p < 0.0001 versus placebo for each vonoprazan group). By 1 h post-dose, vonoprazan was associated with complete relief of significantly more heartburn episodes compared with placebo. No serious treatment-emergent adverse events were reported. On-demand vonoprazan may be a potential alternative to continued daily acid suppression therapy for the relief of episodic heartburn in patients with NERD. gov: NCT04799158.

Puberty suppression followed by testosterone therapy does not impair reproductive potential in female mice.

More adolescents are coming out as transgender each year and are put on puberty blockers to suppress natal puberty, which is then followed by cross-hormone treatment to achieve puberty of the desired gender. Studies to examine the effects of puberty suppression and virilizing therapy on future reproductive potential among transgender males are lacking. This study used a translational murine IVF model to examine the effects of female puberty suppression with depot leuprolide acetate (LA), followed by virilizing therapy with testosterone cypionate (T), on embryologic and pregnancy outcomes. LA effectively inhibited puberty when mice were treated beginning at 3 weeks of age. LA treatment was associated with higher mouse weight but lower ovarian weight. LA-treated mice ovulated developmentally competent eggs in response to gonadotropin administration, albeit at a higher dose than controls. Ovaries from mice treated with LA and T produced oocytes that had morphologically normal meiotic spindles after in vitro maturation, and responded to gonadotropin stimulation. Eggs from mice treated with LA and T were fertilizable and produced developmentally competent embryos that led to births of fertile pups. These results suggest that fertility may not be impaired after puberty suppression and cross-hormone therapy for transgender males.

AP-1/c-Fos supports SIV and HIV-1 latency in CD4 T cells infected in vivo

Persistent HIV-1 reservoirs of infected CD4 Tcells are a major barrier to HIV-1 cure, although the mechanisms by which they are established and maintained invivo remain poorly characterized. To elucidate host cell gene expression patterns that govern virus gene expression, we analyzed viral RNA+ (vRNA) CD4 Tcells of untreated simian immunodeficiency virus (SIV)-infected macaques by single-cell RNA sequencing. A subset of vRNA+ cells distinguished by spliced and high total vRNA (7-10% of reads) expressed diminished FOS, a component of the Activator protein 1 (AP-1) transcription factor, relative to vRNA-low and -negative cells. Conversely, FOS and JUN, another AP-1 component, were upregulated in HIV DNA+ infected cells compared to uninfected cells from people with HIV-1 on suppressive therapy. Inhibiting c-Fos in latently infected primary cells augmented reactivatable HIV-1 infection. These findings implicate AP-1 in latency establishment and maintenance and as a potential therapeutic target to limit HIV-1 reservoirs.

A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo

The immune isolation of cells within devices has the potential to enable long-term protein replacement and functional cures for a range of diseases, without requiring immune suppressive therapy. However, a lack of vasculature and the formation of fibrotic capsules around cell immune-isolating devices limits oxygen availability, leading to hypoxia and cell death in vivo. This is particularly problematic for pancreatic islet cells that have high O2 requirements. Here, we combine bioelectronics with encapsulated cell therapies to develop the first wireless, battery-free oxygen-generating immune-isolating device (O2-Macrodevice) for the oxygenation and immune isolation of cells in vivo. The system relies on electrochemical water splitting based on a water-vapor reactant feed, sustained by wireless power harvesting based on a flexible resonant inductive coupling circuit. As such, the device does not require pumping, refilling, or ports for recharging and does not generate potentially toxic side products. Through systematic in vitro studies with primary cell lines and cell lines engineered to secrete protein, we demonstrate device performance in preventing hypoxia in ambient oxygen concentrations as low as 0.5%. Importantly, this device has shown the potential to enable subcutaneous (SC) survival of encapsulated islet cells, in vivo in awake, freely moving, immune-competent animals. Islet transplantation in Type I Diabetes represents an important application space, and 1-mo studies in immune-competent animals with SC implants show that the O2-Macrodevice allows for survival and function of islets at high densities (~1,000 islets/cm2) in vivo without immune suppression and induces normoglycemia in diabetic animals.

Factors influencing behavioral cough suppression therapy in children with nonspecific chronic cough.

Behavioral cough suppression therapy (BCST) with a speech-language pathologist is a common treatment for chronic nonspecific cough (a.k.a., tic cough) in children. Yet, the outcomes and duration of pediatric BCST have eluded formal investigation. This study examined whether BCST improves cough in children with nonspecific cough and factors that predict the course of treatment. Additionally, the cough characteristics and comorbidities associated with the condition were examined. A retrospective, observational cohort design was utilized. Cough characteristics, medical history, and BCST treatment details and outcomes for 151 children were extracted from the electronic medical record of a large outpatient pediatric otolaryngology clinic. Cough was dry and onset unaccompanied by illness in most cases. Roughly half of patients reported gradual onset and cough proceeded by tickle. On average, patients experienced symptoms for 19 months (SD = 20.09) before diagnosis. Rates of comorbid General Anxiety Disorder were elevated compared to pediatric norms. Additionally, high rates of asthma (22.1%), reflux (62.3%), and disordered sleep breathing (19.2%) were observed. Common findings on laryngoscopy included interarytenoid edema and erythema. Vocal fold changes were observed in 22.9% of children. BCST reduced cough in 92.5% of patients following an average of 1.7 sessions. Comorbid behavioral health diagnoses (p = 0.013) or induced laryngeal obstruction symptoms (p = 0.025) were significant predictors of increased therapy sessions. Cough proceeded by tickle significantly predicted fewer sessions in therapy (p = 0.011). Although randomized clinical trials are needed, these data suggest that BCST is a low-risk, effective treatment for children with nonspecific cough.

Suppressive Antibiotic Therapy After Debridement, Antibiotics, and Implant Retention is Well-Tolerated Without Inducing Resistance: A Multicenter Study

BackgroundSuppressive antibiotic therapy (SAT) after total joint arthroplasty (TJA) debridement, antibiotics, and implant retention (DAIR) maximizes reoperation-free survival. We evaluated SAT after DAIR of acutely infected primary TJA regarding: 1) adverse drug reaction (ADR)/intolerance; 2) reoperation for infection; and 3) antibiotic resistance. MethodsPatients who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA) DAIR for acute periprosthetic joint infection at two academic medical centers from 2015 to 2020 were identified (n = 115). Data were collected on patient demographics, infecting organisms, antibiotics, ADR/intolerances, reoperations, and antibiotic resistances. Median SAT duration was 11 months. Stepwise multivariate logistic regressions were used to identify covariates significantly associated with outcomes of interest. ResultsThere were 11.1 and 16.3% of TKA and THA DAIR patients, respectively, who had ADR/intolerance to SAT. Patients prescribed trimethoprim/sulfamethoxazole (P = .0014) or combination antibiotic therapy (P = .0169) after TKA DAIR had increased risk of ADR/intolerance. There was no difference in reoperation-free survival between TKA (83.3%) and THA (65.1%) DAIR (P = .5900) at mean 2.8-year follow-up. Risk of reoperation for infection was higher among TKA Staphylococcus aureus infections (P = .0004) and lower with increased SAT duration (P < .0450). The optimal duration of SAT was nearly 2 years. No cases of antibiotic resistance developed due to SAT. ConclusionsConsider SAT after TJA DAIR due to improved reoperation-free survival and favorable safety profile. Prolonged SAT did not induce antibiotic resistance. Use trimethoprim/sulfamethoxazole with caution because of the increased likelihood of ADR/intolerance. Level of EvidenceTherapeutic Level III.

Implication of the Autophagy-Related Protein Beclin1 in the Regulation of EcoHIV Replication and Inflammatory Responses.

The protein Beclin1 (BECN1, a mammalian homologue of ATG6 in yeast) plays an important role in the initiation and the normal process of autophagy in cells. Moreover, we and others have shown that Beclin1 plays an important role in viral replication and the innate immune signaling pathways. We previously used the cationic polymer polyethyleneimine (PEI) conjugated to mannose (Man) as a non-viral tool for the delivery of a small interfering (si) Beclin1-PEI-Man nanoplex, which specifically targets mannose receptor-expressing glia (microglia and astrocytes) in the brain when administered intranasally to conventional mice. To expand our previous reports, first we used C57BL/6J mice infected with EcoHIV and exposed them to combined antiretroviral therapy (cART). We show that EcoHIV enters the mouse brain, while intranasal delivery of the nanocomplex significantly reduces the secretion of HIV-induced inflammatory molecules and downregulates the expression of the transcription factor nuclear factor (NF)-kB. Since a spectrum of neurocognitive and motor problems can develop in people living with HIV (PLWH) despite suppressive antiretroviral therapy, we subsequently measured the role of Beclin1 in locomotor activities using EcoHIV-infected BECN1 knockout mice exposed to cART. Viral replication and cytokine secretion were reduced in the postmortem brains recovered from EcoHIV-infected Becn1+/- mice when compared to EcoHIV-infected Becn1+/+ mice, although the impairment in locomotor activities based on muscle strength were comparable. This further highlights the importance of Beclin1 in the regulation of HIV replication and in viral-induced cytokine secretion but not in HIV-induced locomotor impairments. Moreover, the cause of HIV-induced locomotor impairments remains speculative, as we show that this may not be entirely due to viral load and/or HIV-induced inflammatory cytokines.

Differentiated thyroid cancer - possible risks of treatment, suppressive therapy and adherence to current recommendations.

Thyroid carcinoma (TC) is rare and represents 1-2 % of all human tumors. The incidence of TC has been increasing worldwide. TC comprises of a heterogeneous group of tumours with variable biological activity. Women are mostly affected. TC can be divided in differentiated TC/DTCs (papillary - PTC, follicular - FTC, from Hürthle cells - HCC), medullary carcinoma - MTC and anaplastic thyroid cancer - ATC. In this article, we focus on possible pitfalls of suppression therapy (cardiovascular, bone and mental), particularly in low-risk patients, and we discuss the data on the adherence to guidelines for suppression therapy in DTC.

The Safety and Efficacy of Acid Suppression Therapy in Neonatal GERD

Gastroesophageal reflux (GER) is a common physiologic process in infants that often resolves with growth and maturation, while gastroesophageal reflux disease (GERD) is a serious and common referral disease in infants and neonates. The first-line treatment for both GER and GERD is conservative therapy. H2RAs and PPIs are the two basic pharmacologic agents in the treatment of GERD in pediatrics and adults. The efficacy of PPIs is higher than that of H2RAs in GERD treatment. There are controversies in the pharmacologic treatment of neonatal GERD, and performing more clinical trials to survey the effect of PPIs and H2RAs and compare them with each other is necessary in this age group. We conducted three different clinical trials to compare the efficacy and safety of ranitidine with omeprazole or lansoprazole in refractory neonatal GERD.