Pegylated Interferon Alpha for Chronic Hepatitis B Virus Infection

Chronic hepatitis B (CHB) is a potentially life-threatening and prevalent disease worldwide. Far from attaining the ultimate treatment goal, hepatitis B virus (HBV) infection eradication, the two current therapeutic options aim to prevent progression to end-stage liver disease, maintaining long-term suppression of HBV replication. Pegylated interferon-α (PEG-INFα) is often poorly tolerated and disregarded considering the orally administered nucleos(t)ide analogues. However, PEG-INFα may achieve similar treatment endpoints with a finite course of treatment. We report a case of PEG-INFα-treated CHB that attained sustained off-treatment virological response with only 16 weeks of treatment, with loss of both HBeAg and HBsAg (this latter the optimal treatment endpoint).

Using Observational Study Data as an External Control Group for a Clinical Trial: an Empirical Comparison of Methods to Account for Longitudinal Missing Data

Background: Observational data are increasingly being used to conduct external comparisons to clinical trials. In this study, we empirically examined whether different methodological approaches to longitudinal missing data affected study conclusions in this setting. Methods: We used data from one clinical trial and one prospective observational study, both Norwegian multicenter studies including patients with recently diagnosed rheumatoid arthritis and implementing similar treatment strategies, but with different stringency. A binary disease remission status was defined at 6, 12, and 24 months in both studies. After identifying patterns of longitudinal missing outcome data, we evaluated the following five approaches to handle missingness: analyses of patients with complete follow-up data, multiple imputation (MI), inverse probability of censoring weighting (IPCW), and two combinations of MI and IPCW. Results: We found a complex non-monotone missing data pattern in the observational study (N=328), while missing data in the trial (N=188) was monotone due to drop-out. In the observational study, only 39.0% of patients had complete outcome data, compared to 89.9% in the trial. All approaches to missing data indicated favorable outcomes of the treatment strategy in the trial and resulted in similar study conclusions. Variations in results across approaches were mainly due to variations in estimated outcomes for the observational data. Conclusions: Five different approaches to handle longitudinal missing data resulted in similar conclusions in our example. However, the extent and complexity of missing observational data affected estimated comparative outcomes across approaches, highlighting the need for careful consideration of methods to account for missingness when using observational data as external controls to trial data.

Development of a Screening Tool for Feet/Footwear- Related Influences on Fall Risk

The effectiveness of multifactorial fall risk assessment and intervention strategies is well documented. Although identifying feet/footwear-related influences on fall risk is a vital fall risk assessment component, few evidence-based resources or screening tools are available. To address this need, we developed the Screening Tool for Feet/Footwear-Related Influences on Fall Risk. Our tool is designed for older adults who are identified as at risk for falling, based on the CDC’s Stopping Elderly Accidents, Deaths, and Injuries (STEADI) Algorithm for Fall Risk Screening, Assessment, and Intervention. Tool development was informed by results of our systematic review of lower-limb factors associated with balance and falls. Our initial tool was evaluated by an external group of 9 interprofessional content experts. Those experts recommended modification of 8 items and rated the tool’s clarity as 81.2/100, appeal as 79.1/100, and clinical feasibility as 76.1/100. After incorporating recommended changes, we completed a modified Delphi study using 8 new interprofessional experts (average years of experience: 19.3). During Phase 1, Delphi participants recommended we combine items with similar treatment recommendations, add a question about orthoses, and increase the specificity of 9 items. This refinement resulted in a 20-item screening tool, which met approval after two rounds of consensus voting. Approval was defined based on the Item Content Validation Index, percentage of agreement > 80% on each item. The high level of agreement illustrates the tool’s content validity. Using our tool, an older adult’s feet/footwear-related risk factors can be identified and incorporated into an effective multifactorial fall prevention intervention.

Therapeutic effects of Probiotic Ointment for Atopic Dermatitis

The human microbiome is an integral part of the body, playing a crucial role in metabolism, energy homeostasis, the regulation of the immune system, and others. The study aims to examine the effect of probiotic ointment on the qualitative composition of the lesional skin microbiome in patients with atopic dermatitis. The study population consisted of 110 patients aged 20 to 45 years with mild atopic dermatitis (AD). The patients were divided into two groups. One group received four different medications: levocetirizine dihydrochloride, enterosgel, topical Tizol gel, and topical 1% hydrocortisone ointment. The other group received a similar treatment with four different medications: levocetirizine dihydrochloride, enterosgel, topical Tizol gel, and topical probiotic ointment. The treatment period was one month. After treatment, the frequency and intensity of the main AD symptoms significantly decreased. A load of S. aureus fell in the probiotic-treated group from 73.4% to 29.1% (p<.05). In the standard-treated group, the S. aureus load decreased from 78.2% to 43.6% (p<.05). The study found that the standard treatment without probiotics helped to decrease S. aureus colonisation in AD patients by 2.00 times (p<.05), whereas using the probiotic ointment reduced S. aureus colonisation by 3 times (p<.05).

A Case of Terbinafine-Resistant Tinea Cruris Caused by Trichophyton tonsurans

A 26-year-old male patient referred to our center with a history of extremely itchy crusted skin lesions in his groins for one year. Moreover, his friend, a 25-year-old male, also developed similar lesions in the groin after using the shared pool, whose condition also did not improve with similar treatment. A regular mycology test (direct and culture test) was performed, as well as molecular examination. The antifungal susceptibility assay to terbinafine, itraconazole, posaconazole, fluconazole, and voriconazole was conducted according to the Clinical and Laboratory Standards Institute M38 third ed. The sequencing study identified T. tonsurans as the causative organism in both patients. The abovementioned organism isolated from both patients displayed resistance against terbinafine and fluconazole (MIC ≥ 4 µg/ml and MIC ≥ 8 µg/ml, respectively). Moreover, the susceptibility of both subjects to posaconazole (0.313 µg/ml), voriconazole (0.25–0.0625 µg/ml), and (1 µg/ml) itraconazole increased. The present report aimed to emphasize the increase in antifungal resistance and a demand for antifungal stewardship, to control this public health threat.

Predicting pelvic congestion syndrome: Concomitant pelvic pain diagnoses do not affect venography or embolization outcomes

Objectives: Pelvic congestion syndrome (PCS) is a challenging diagnosis to make secondary to nonspecific presenting symptoms and imaging findings. This retrospective review aims to discern predictive factors which can guide the decision to perform catheter-based venography and prognosticate outcomes. Material and Methods: A retrospective analysis of patients who underwent catheter venography for PCS between January 2014 and December 2019 was performed. Multiple factors, including patient demographics, clinical history, pre-procedural imaging, venographic findings, and treatment outcomes 180 days post-procedure, were included in the analysis. Venographic findings were used to separate patients into two groups (positive or negative), with these factors compared across groups. Regression analysis controlled for the confounding effects of age and body mass index (BMI). Treated subjects were separated based on outcome (partial, no response, complete response, or technical failure), and comparisons were performed. Results: Eighty patients were included in the initial analysis. Two patients were excluded due to prior embolization or portal hypertension. Seventy-eight patients were included in the final analysis. Sixty-two patients had positive findings, and 16 had no venographic findings to suggest PCS. A history of prior pregnancy was a significant predictor of positive venographic results (odds ratio = 5.99, P = 0.007). BMI was significantly lower in those with positive venographic results (P = 0.047). Presence of concomitant diagnoses did not affect venographic findings or treatment outcomes. No factors predicted treatment outcomes. Five of the treated patients had subsequent successful pregnancies. Conclusion: A lower BMI supports the decision to perform venography for suspected PCS. In addition, patients who carried concomitant potentially confounding diagnoses for chronic pelvic pain were found to have similar rates of venographic findings suggesting PCS, as well as similar treatment outcomes.

Uncovering the Sex-Specific Endocrine Responses to Reproduction and Parental Care

Hormones mediate physiological and behavioral changes in adults as they transition into reproduction. In this study, we characterize the circulating levels of five key hormones involved in reproduction in rock doves (Columba livia): corticosterone, progesterone, estradiol, testosterone, and prolactin using univariate and multivariate approaches. We show similar patterns as previous studies in the overall patterns in circulating levels of these hormones, i.e., testosterone (males) and estradiol (females) high during nest-building or egg-laying, prolactin increasing at mid-incubation and peaking at hatching (both sexes), and elevated corticosterone levels in later incubation and early nestling development. In our investigation of hormone co-variation, we find a strong correlation between prolactin and corticosterone across sampling stages and similarities in earlier (early to mid-incubation) compared to later (late incubation to nestling d9) sampling stages in males and females. Finally, we utilized experimental manipulations to simulate nest loss or altered caregiving lengths to test whether external cues, internal timing, or a combination of these factors contributed most to hormone variation. Following nest loss, we found that both males and females responded to the external cue. Males generally responded quickly following nest loss by increasing circulating testosterone, but this response was muted when nest loss occurred early in reproduction. Similar treatment type, e.g., removal of eggs, clustered similarly in hormone space. These results suggest internal drivers limited male response early in reproduction to nest loss. In contrast, circulating levels of these hormones in females either did not change or decreased following nest manipulation suggesting responsiveness to external drivers, but unlike males, this result suggests that reproductive processes were decreasing.

Dynamin-2 Deficiency Causes Neutropenia and Dysplastic Bone Marrow Changes in an Age and Sex Dependent Manner in Mice

The dynamins are a family of ubiquitously expressed proteins with GTPase activity and are known for their role in membrane remodeling and intracellular trafficking. However, their exact role within various hematopoietic lineages is incompletely understood. In humans, most of the clinical cases with cytopenia in Charcot-Marie-Tooth (CMT) disease due to dynamin-2 mutations are associated with neutropenia, and CMT patients may suffer from impaired wound healing. Of interest, pregnancy notably worsens CMT disease, possibly due to hormonal changes. Antiprogesterone treatment was successfully given in a CMT rat model, and similar treatment is being considered for human CMT. We previously reported that inhibiting dynamin (DNM) activity impairs migration capability in mature megakaryocytes. We obtained the conditional deletion of Dnm2 and targeted its deletion in hematopoietic tissues with the vav-cre murine strain. Homozygous deletion of Dnm2 in blood tissues appears embryonic lethal. None of the pups born showed a Vav-cre/Dnm-2 fl/fl genotype, whereas a third of the pups born had a Vav-cre/Dnm-2 fl/wt (Dnm2 het) genotype. Bone marrow cells from the heterozygous female mice (Dnm2 het) had 35% to 50% decreased Dnm2 expression in comparison with age-matched controls (CTRL). Evaluation of the complete blood counts demonstrated that Dnm2 het female mice developed leukopenia which was detected from 40 weeks of age (average granulocyte-monocyte counts: CTRL 532/mm3 vs. Dnm2 het 300/mm3; p=0.0164). Neutropenia was unequivocal at 65 weeks of age (average neutrophil counts, CTRL 700/mm3 vs. Dnm2 het 343/mm3, p=0.016). Dnm2 het showed a trend for higher platelet counts than controls, but this was non-statistically significant. Further analysis of hematopoietic lineage maturation by flow cytometry indicated that lineage-negative cells and granulocyte-monocyte progenitors were decreased in Dnm2 het mice (average bone marrow lineage-negative cells: CTRL 2.8x10E6 vs. Dnm2 het 1.97x10E6, p =0.0056; average granulocyte-monocyte progenitors: CTRL 1.35x10E6 vs. Dnm2 het 0.85x10e6, p=0.01), along with a relative increase of common lymphoid progenitors and of megakaryocyte/erythrocyte progenitors in the bone marrow. Immunohistochemical staining for mature neutrophils with Ly6G showed an overall decreased number of mature granulocytes in the bone marrow of Dnm2 het mice (average Ly6G-positive cells: CTRL 20% vs. Dnm2 het 29%, p=0.0026). A linear pattern of distribution of Ly6G positive bone marrow cells along blood vessels was observed in fewer mice in the Dnm2 het group than in the CTRL group (25% vs. 59%, p=0.02), indicating that the migration pattern within the bone marrow is altered in the Dnm2 het group (see Figure). In addition, Dnm2 het mice developed splenomegaly (average spleen weight: Dnm2 het 146 mg vs. CTRL 99 mg, p=0.006), which was secondary to a marked florid reactive germinal center hyperplasia. Some of the Dnm2 het mice, including 5 mice whose pregnancy occurred in middle-age (p=0.005 when comparing with CTRL or young Dnm2 het mice) and 2 non-pregnant older mice, showed physical signs of distress with markedly reduced activity, poor grooming, ruffled furs, and hunched posture. Both non-pregnant sick mice showed a marked decrease in Ly6G positive mature neutrophils at 0.3% of total marrow cells (Figure), and the bone marrow from one mouse was completely effaced by immature myeloid precursors, consistent with the development of acute myeloid leukemia. In addition, a third of Dnm2 hetmice showed no distress but displayed morphological bone marrow abnormalities including megakaryocytic dysmorphology. In summary, female mice with loss of Dnm2 in the hematopoietic compartment develop persistent neutropenia as they age, with decreased granulocyte progenitor production and with migration defects. These abnormalities are associated with a risk for developing megakaryocytic dysplasia, and acute myeloid leukemia. These findings might also suggest a mechanism for chronic idiopathic neutropenia, which has a predominance in middle-aged women. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Injection site sarcomas in other species than the domestic cat

Injection site sarcomas (ISS) are tumours of tissues of mesenchymal origin that occur at an injection site. These tumours have been mainly described in cats as Feline injection-site sarcoma (FISS), but suspected cases have also been described in other species such as dogs. In other species than the domestic cat, these tumours are however much rarer. As a result, the body of literature is limited. This review aims to summarize the knowledge regarding ISS in species other than the domestic cat. In general, it seems that ISS can occur in a wide range of animals and that similar treatment strategies are employed as in cats. Like in cats, it seems that the benefit of the reasons for injection (such as vaccination and microchip implantation) could outweigh the risk of ISS development in other species.

Legally Mandated, Formally Pressured, or Voluntary Anger Treatment: Associations With Treatment Recommendations, Refusal, and Completion

Legally mandated treatment is common in the criminal justice system, for example, for anger management, substance misuse, and intimate partner violence. Past studies have compared voluntary and legally mandated treatment participants but have not distinguished a third, in-between group that is formally pressured to participate in treatment, but not mandated by the criminal justice system. The current study aimed to assess differences on individual characteristics (e.g., sociodemographic and psychiatric) and baseline measures of psychopathology (e.g., anger, aggression, and depression) across three levels of voluntariness and to determine whether voluntariness was associated with treatment recommendation, refusal, and completion at an outpatient anger treatment clinic. Data were retrospectively gathered from the clinical charts of 405 participants. Referrals were classified as voluntary (e.g., self-referred, 61%), formally pressured (e.g., required by work, 14%), or legally mandated (e.g., court order, 25%). Legally mandated participants were younger, more likely to have substance use disorder, less likely to be women, to have a high school education, or to be on psychiatric medications compared to the other two groups. Voluntary participants scored higher on measures of self-reported anger, depression, and stress than the legally mandated participants. Legally mandated participants in particular presented with non-clinical levels of anger and aggression. Level of voluntariness did not affect the decision to recommend individual or group therapy after an intake assessment, but legally mandated participants were significantly more likely ( OR = 2.30) than voluntary participants to refuse recommended treatment. Level of voluntariness did not have a significant association with treatment completion. Findings support our distinction between legally mandated and formally pressured participants, but do not support previous research that suggests legally mandated individuals have lower attrition rates in similar treatment programs. The study has implications for the criminal justice system and for anger treatment programs who admit participants with varying levels of voluntariness.