Search

Simple Summary: Squamous cell carcinoma of the anus or anal cancer is increasing in prevalence, and the standard treatment of mitomycin and 5-fluorouracil is too toxic for many patients. Unfortunately, there is currently no standard of care for what to do for this disease when someone is not a candidate for this aggressive treatment. Here, we demonstrate the promising preliminary toxicity profile and efficacy of the combination of weekly carboplatin and paclitaxel chemotherapy for patients with localized anal cancer. This regimen was able to complete 80% of the intended treatments with anticipated toxicities, and 89% achieved a complete clinical response. This combination is a promising regimen and is already being investigated further in a clinical trial. Background: Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. Methods: From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. Results: Ten patients were included; eight were female, and the median age was 75.5 years (54–87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m2), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40–100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4–50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). Conclusions: This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Background: Induction therapy with depleting antibodies in the setting of liver transplantation (LT) is discussed controversially to this day. The rabbit antithymocyteglobulin (ATG) Thymoglobulin (rATG) was introduced as early as 1984 and was frequently used as a standard regime for induction therapy after LT. There are no public reports characterizing Grafalon (ATG-F), a novel ATG, as an induction agent after LT. Objectives: The aim of this observational non-interventional study was to investigate the safety and efficacy of Grafalon induction therapy and characterize its clinical effects in the setting of LT. Methods: A cohort of 80 patients undergoing deceased donor LT at the Medical University of Vienna and receiving Grafalon as part of the clinical standard immunosuppressive regimen was prospectively included between March 2021 and November 2022. Patients were monitored closely for leukocytopenia and thrombocytopenia during the first postoperative week and followed up for incidence and severity of biopsy-proven acute rejection (BPAR), overall survival, and bacterial infections in the first year after LT. Results: The incidences of thrombocytopenia and leukocytopenia following Grafalon treatment peaked on postoperative day four, with 64% and 31%, respectively. However, there were no cases of severe leukocytopenia after the first postoperative week. Induction therapy with Grafalon resulted in a rate of localized bacterial infections and bacteremia of 28% and 21%, respectively. The rate of BPAR was 12.5% in the first year after LT; the one-year survival rate in this cohort was 90%. Conclusions: Overall, this study provides evidence of the safety and efficacy of Grafalon as an induction agent. Further studies investigating the potential long-term effects of Grafalon, as well as comparison studies with different immunosuppressive regimens, are needed in order to draw further conclusions. [ABSTRACT FROM AUTHOR]

COVID-19, caused by SARS-CoV-2, and its variants have spread rapidly across the globe in the past few years, resulting in millions of deaths worldwide. Hematological diseases and complications associated with COVID-19 severely impact the mortality and morbidity rates of patients; therefore, there is a need for oversight on what pharmaceutical therapies are prescribed to hematologically at-risk patients. Thrombocytopenia, hemoglobinemia, leukopenia, and leukocytosis are all seen at increased rates in patients infected with COVID-19 and become more prominent in patients with severe COVID-19. Further, COVID-19 therapeutics may be associated with hematological complications, and this became more important in immunocompromised patients with hematological conditions as they are at higher risk of hematological complications after treatment. Thus, it is important to understand and treat COVID-19 patients with underlying hematological conditions with caution. Hematological changes during COVID-19 infection and treatment are important because they may serve as biomarkers as well as to evaluate the treatment response, which will help in changing treatment strategies. In this literature review, we discuss the hematological complications associated with COVID-19, the mechanisms, treatment groups, and adverse effects of commonly used COVID-19 therapies, followed by the hematological adverse events that could arise due to therapeutic agents used in COVID-19. [ABSTRACT FROM AUTHOR]

Background and Objectives: The Wakayama prefecture is endemic for two types of tick-borne rickettsioses: Japanese spotted fever (JFS) and scrub typhus (ST). Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne hemorrhagic viral disease with a high mortality rate and is often difficult to differentiate from such rickettsioses. SFTS cases have recently increased in Wakayama prefecture. For early diagnosis, this study aimed to evaluate the clinical characterization of such tick-borne infections in the co-endemic area. Materials and Methods: The study included 64 febrile patients diagnosed with tick-borne infection in Wakayama prefecture between January 2013 and May 2022. Medical records of 19 patients with SFTS and 45 with rickettsiosis (JSF, n = 26; ST, n = 19) were retrospectively examined. The receiver operating curve (ROC) and area under the curve (AUC) were calculated to evaluate potential factors for differentiating SFTS from rickettsiosis. Results: Adults aged ≥70 years were most vulnerable to tick-borne infections (median, 75.5 years; interquartile range, 68.5–84 years). SFTS and rickettsiosis occurred mostly between summer and autumn. However, no significant between-group differences were found in age, sex, and comorbidities; 17 (89%) patients with SFTS, but none of those with rickettsiosis, experienced gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. Meanwhile, 43 (96%) patients with rickettsiosis, but none of those with SFTS, developed a skin rash. The AUCs of white blood cells (0.97) and C-reactive protein (CRP) levels (0.98) were very high. Furthermore, the differential diagnosis of SFTS was significantly associated with the presence of gastrointestinal symptoms (AUC 0.95), the absence of a skin rash (AUC 0.98), leukopenia <3.7 × 109/L (AUC 0.95), and low CRP levels < 1.66 mg/dL (AUC 0.98) (p < 0.001 for each factor). Conclusions: Clinical characteristics and standard laboratory parameters can verify the early diagnosis of SFTS in areas where tick-borne infections are endemic. [ABSTRACT FROM AUTHOR]

Azathioprine (AZA) has demonstrated efficacy in multiple randomized control trials (RCTs) for Relapsing-Remitting Multiple Sclerosis (RRMS). However, we still need comparative real-world data with other first-line disease-modifying therapies (DMTs). We aimed to assess AZA's effectiveness regarding relapses, disability progression, time to the first relapse, magnetic resonance imaging (MRI) activity, and safety compared with other approved first-line DMTs in an Indian population in a real-world setting. We conducted a single-center prospective study of treatment-naive RRMS patients between 2017 and 2019. We evaluated the effects of AZA and other approved DMTs on clinical and radiological measures. Among 192 eligible patients (F:M ratio 2.84:1), 68 patients (35.4%) were on AZA, 68 patients (35.4%) were on dimethyl fumarate (DMF), 32 patients (16.7%) on interferon (IFN beta-1a), and 16 patients (8.3%) on teriflunomide (TFL). Four treatment groups were comparable: AZA v/s DMF v/s TFL v/s IFN beta-1a. In primary outcomes, there was no significant difference between the groups in terms of change in the Expanded Disability Status Scale (EDSS) score at three months (p-value = 0.169), six months (p-value = 0.303), 12 months (p-value = 0.082), and 24 months (p-value = 0.639), the number of relapses (p-value = 0.229), and time to the first relapse (p-value > 0.05 in all groups). In the secondary outcome, there was no significant difference between the treatment groups on serial MRI parameters used according to "Magnetic Resonance Imaging in Multiple Sclerosis" (MAGNIMS) 2016 criteria (p-value > 0.05). In safety outcomes, leukopenia was significantly more common in the AZA group (p-value = 0.025), flu-like symptoms (p-value = 0.0001), and injection site reactions (p-value = 0.035) were significantly more common in the IFN beta-1a group. Our study suggests AZA is as effective as other approved DMTs and a good alternative as a first-line treatment for multiple sclerosis's clinical and radiological activity in real-world settings on short follow-up. Based on these results, more randomized controlled trials of AZA v/s DMF or other DMTs are needed for more robust outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer treatments often have side effects that may impair patients' quality of life. Our research aimed to create a predictive tool able to foresee the likelihood of these severe complications. We used medical data from 267 gastrointestinal cancer patients, applied a particular type of computer model known as a Bayesian network, and evaluated its predictions against real outcomes. The model accurately predicted the risk of developing severe haematological toxicity in 80–85% of cases. This tool, if further validated and refined, may help to identify a vulnerable subset of patients who might benefit from personalized treatment plans. Purpose: Severe toxicity is reported in about 30% of gastrointestinal cancer patients receiving 5-Fluorouracil (5-FU)-based chemotherapy. To date, limited tools exist to identify at risk patients in this setting. The objective of this study was to address this need by designing a predictive model using a Bayesian network, a probabilistic graphical model offering robust, explainable predictions. Methods: We utilized a dataset of 267 gastrointestinal cancer patients, conducting preprocessing, and splitting it into TRAIN and TEST sets (80%:20% ratio). The RandomForest algorithm assessed variable importance based on MeanDecreaseGini coefficient. The bnlearn R library helped design a Bayesian network model using a 10-fold cross-validation on the TRAIN set and the aic-cg method for network structure optimization. The model's performance was gauged based on accuracy, sensitivity, and specificity, using cross-validation on the TRAIN set and independent validation on the TEST set. Results: The model demonstrated satisfactory performance with an average accuracy of 0.85 (±0.05) and 0.80 on TRAIN and TEST datasets, respectively. The sensitivity and specificity were 0.82 (±0.14) and 0.87 (±0.07) for the TRAIN dataset, and 0.71 and 0.83 for the TEST dataset, respectively. A user-friendly tool was developed for clinical implementation. Conclusions: Despite several limitations, our Bayesian network model demonstrated a high level of accuracy in predicting the risk of developing severe haematological toxicity in gastrointestinal cancer patients receiving 5-FU-based chemotherapy. Future research should aim at model validation in larger cohorts of patients and different clinical settings. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection is the most common opportunistic infection that occurs following orthotopic liver transplantation (OLT). In addition to the direct infection-related symptoms, it also triggers an immunological response that may contribute to adverse clinical outcomes. CMV disease has been described as a predictor of invasive fungal infections (IFIs) but its role under an antiviral prophylaxis regimen is unclear. Methods: We retrospectively analyzed the medical records of 214 adult liver transplant recipients (LTRs). Universal antiviral prophylaxis was utilized in recipients with CMV mismatch; intermediate- and low-risk patients received pre-emptive treatment. Results: Six percent of patients developed CMV disease independent of their serostatus. The occurrence of CMV disease was associated with elevated virus load and increased incidence of leucopenia and IFIs. Furthermore, CMV disease was associated with higher one-year mortality and increased relapse rates within the first year of OLT. Conclusions: CMV disease causes significant morbidity and mortality in LTRs, directly affecting transplant outcomes. Due to the increased risk of IFIs, antifungal prophylaxis for CMV disease may be appropriate. Postoperative CMV monitoring should be considered after massive transfusion, even in low-risk serostatus constellations. In case of biliary complications, biliary CMV monitoring may be appropriate in the case of CMV-DNA blood-negative patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Oligometastasis is defined as a malignancy disease characterized by a limited number of metastatic foci (3–5). In studies of lung cancer and prostate cancer, local treatment such as radiotherapy or surgery increased the prognosis of oligometastases. The efficacy of local treatment for oligometastasis of hepatocellular carcinoma is not well known. This meta-analysis reports that active local treatment of oligometastases in hepatocellular carcinoma significantly increased survival rates and improved survival outcomes. Although recent studies have shown favorable results after local treatment for oligometastases, the clinical decision of applying local treatment for oligometastatic hepatocellular carcinoma (HCC) remains controversial. This meta-analysis aimed to investigate the benefits of local treatment for HCC oligometastases. Pubmed, Embase, Medline, and the Cochrane library were searched for studies until 1 May 2022. Clinical studies involving at least five cases of HCC oligometsatases treated with local modalities were included. The primary endpoint was overall survival (OS). The benefit of local treatment was assessed as the pooled odds ratio (OR) among comparative series, and the pooled OS percentile was calculated from all studies including patients treated with local treatment. Complications of grade ≥ 3 were assessed subjectively. A total of 10 studies involving 527 patients were included. Radiotherapy and radiofrequency ablation (RFA) were mainly performed (six and five studies) as local modalities treating oligometastases. Pooled OR of comparative series favored the use of local treatment (4.664, 95% confidence interval [CI]: 2.595–8.380, p < 0.001, I2: ~0.0%). Including all cohorts with patients who underwent local treatment, pooled rates of 1-year OS were 71.8% (95% CI: 59.0–81.9; I2 = 81.5%), and pooled 2-year OS were 43.3% (95% CI: 29.1–59.6; I2 = 85.4%). Except for temporal or pre-existing toxicities, grade ≤ 3 complications were reported less than 10% in most studies, although common toxicities include pneumothorax and hematologic deficiency after RFA and radiotherapy, respectively. Grade 5 toxicity has not yet been reported. This systematic review supports the application of local treatment for treating HCC oligometastases. [ABSTRACT FROM AUTHOR]

Intensified preoperative chemotherapy after (chemo)radiotherapy, (Total Neoadjuvant Therapy–TNT), increases pathological complete response (pCR) rates and local control. In cases of clinically complete response (cCR) and close follow-up, non-operative management (NOM) is feasible. We report early outcomes and toxicities of a long-term TNT regime in a single-center cohort. Fifteen consecutive patients with distal or middle-third locally advanced rectal cancer (UICC stage II–III) were investigated, who received neoadjuvant chemoradiotherapy (total adsorbed dose: 50.4 Gy in 28 fractions and two concomitant courses 5-fluorouracil (250 mg/m2/d)/oxaliplatin (50 mg/m2), followed by consolidating chemotherapy (nine courses of FOLFOX4). NOM was offered if staging revealed cCR 2 months after TNT, with resection performed otherwise. The primary endpoint was complete response (pCR + cCR). Treatment-related side effects were quantified for up two years after TNT. Ten patients achieved cCR, of whom five opted for NOM. Ten patients (five cCR and five non-cCR) underwent surgery, with pCR confirmed in the five patients with cCR. The main toxicities comprised leukocytopenia (13/15), fatigue (12/15) and polyneuropathy (11/15). The most relevant CTC °III + IV events were leukocytopenia (4/15), neutropenia (2/15) and diarrhea (1/15). The long-term TNT regime resulted in promising response rates that are higher than the response rates of short TNT regimes. Overall tolerability and toxicity were comparable with the results of prospective trials. [ABSTRACT FROM AUTHOR]

Radiology plays a crucial role for the diagnosis and management of COVID-19 patients during the different stages of the disease, allowing for early detection of manifestations and complications of COVID-19 in the different organs. Lungs are the most common organs involved by SARS-CoV-2 and chest computed tomography (CT) represents a reliable imaging-based tool in acute, subacute, and chronic settings for diagnosis, prognosis, and management of lung disease and the evaluation of acute and chronic complications. Cardiac involvement can be evaluated by using cardiac computed tomography angiography (CCTA), considered as the best choice to solve the differential diagnosis between the most common cardiac conditions: acute coronary syndrome, myocarditis, and cardiac dysrhythmia. By using compressive ultrasound it's possible to study the peripheral arteries and veins and to exclude the deep vein thrombosis, directly linked to the onset of pulmonary embolism. Moreover, CT and especially MRI can help to evaluate the gastrointestinal involvement and assess hepatic function, pancreas involvement, and exclude causes of lymphocytopenia, thrombocytopenia, and leukopenia, typical of COVID-19 patients. Finally, radiology plays a crucial role in the early identification of renal damage in COVID-19 patients, by using both CT and US. This narrative review aims to provide a comprehensive radiological analysis of commonly involved organs in patients with COVID-19 disease. [ABSTRACT FROM AUTHOR]

Placement of image-guided tunneled and non-tunneled large-bore central venous catheters (CVCs) are common procedures in interventional radiology. Although leukopenia and/or thrombocytopenia are common at the time of placement, the roles these factors may have in subsequent catheter-related infection have yet to be investigated. A single-institution retrospective review was performed in patients who underwent CVC placement in interventional radiology between 11/2018–6/2019. The electronic medical record was used to obtain demographics, procedure details, pre-placement laboratory values, and the subsequent 90-day follow-up. A total of 178 tunneled and non-tunneled CVCs met inclusion criteria during this time period. White blood cell (WBC) and platelet counts were found to be significant risk factors for subsequent infection. Administration of pre-procedure antibiotics was not found to be a significant factor for subsequent infection (p = 0.075). Leukopenia and thrombocytopenia at the time of CVC placement are both risk factors of line infection for tunneled large-bore CVCs. This should lead to the consideration of using a non-tunneled CVC when clinically feasible, or the delayed placement of these catheters until counts recover. [ABSTRACT FROM AUTHOR]

Oral candidosis is the most common fungal infection that frequently occurs in patients debilitated by other diseases or conditions. No candidosis happens without a cause; hence oral candidosis has been branded as a disease of the diseased. Prior research has identified oral candidosis as a mark of systemic diseases, such as hematinic deficiency, diabetes mellitus, leukopenia, HIV/AIDS, malignancies, and carbohydrate-rich diet, drugs, or immunosuppressive conditions. An array of interaction between Candida and the host is dynamic and complex. Candida exhibits multifaceted strategies for growth, proliferation, evasion of host defenses, and survival within the host to induce fungal infection. Oral candidosis presents a variety of clinical forms, including pseudomembranous candidosis, erythematous candidosis, angular cheilitis, median rhomboid glossitis, cheilocandidosis, juxtavermillion candidosis, mucocutaneous candidosis, hyperplastic candidosis, oropharyngeal candidosis, and rare suppurative candidosis. The prognosis is usually favorable, but treatment failure or recurrence is common due to either incorrect diagnosis, missing other pathology, inability to address underlying risk factors, or inaccurate prescription of antifungal agents. In immunocompromised patients, oropharyngeal candidosis can spread to the bloodstream or upper gastrointestinal tract, leading to potentially lethal systemic candidosis. This review therefore describes oral candidosis with regard to its pathophysiology and best practice for diagnosis, practical classification, and successful management [ABSTRACT FROM AUTHOR]

Since the beginning of the COVID-19 pandemic, there have been numerous reports and reviews on the complications caused by the disease, analyzing the acute and chronic consequences. The main symptoms of SARS-CoV-2 are dry cough, fever, and fatigue. COVID-19 appears to affect all systems, including renal, cardiovascular, circulatory, and respiratory systems, causing chronic obstructive pulmonary disease. We report on a 14-year-old male adolescent, who presented with thrombocytopenia (platelet count 92 × 109 /L) and leukopenia (white blood count 4.2 × 103 /μL) that was observed two months ago. Ten days before the first blood test, a viral infection with nasal congestion and runny nose was reported, without other accompanying symptoms. Viral antibodies screening revealed positivity for all the three specific COVID-19 antibodies. Further haematological evaluation with bone marrow aspiration revealed non-specific dysplastic features of the red cell and megakaryocyte progenitors. Although haematological alterations due to COVID-19 infection are available from adult patients’ reports, the effect of COVID-19 infection in the pediatric population is underestimated and this is the first case with such haematological involvement. Noteworthy, in the current case, the impact of the COVID-19 infection was not related to the severity of the disease, as the symptoms were mild. In similar cases, bone marrow aspiration would not be performed as a part of routine work-up. Thus, it is important when evaluating pediatric patients with COVID-19 infection to search and report those alterations in order to better understand the impact and the spectrum of clinical manifestations of the specific viral infection in children and adolescents. [ABSTRACT FROM AUTHOR]

Ziyuglycoside I (ZGS1) is a promising drug candidate for the treatment of leucopenia. Currently, information on ZGS1 and its in vivo metabolite ziyuglycoside II (ZGS2) is limited. The objective of this study was to investigate the pharmacokinetics, tissue distribution, and excretion of ziyuglycoside I (ZGS1) and its metabolite ziyuglycoside II (ZGS2) in rats. In our study, a simple and sensitive high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method was established for simultaneous determination of ZGS1 and its metabolite for Sprague-Dawley rat pharmacokinetics studies. The method was validated following internationally-approved guidelines. The results presented in this study indicated that subcutaneous administration of ZGS1 prolonged its extension time and increased the area under the curve (AUC0-t) of ZGS2 during 0 to t minutes. In summary, in this study, the pharmacokinetic characteristics of ZGS1 and its metabolite ZGS2 were defined and its tissue distribution, and excretion in rats were described. Our finding may be beneficial for leucopenia drug that focus on ZGS1. [ABSTRACT FROM AUTHOR]

Background The use of bevacizumab in the management of glioblastoma multiforme (GBM) remains controversial. In Canada, bevacizumab is approved for the treatment of recurrent GBM. We describe a pattern of progression across treatment lines in GBM. Methods During 2008-2014, 64 patients diagnosed with GBM were treated with bevacizumab at McGill University hospitals. Of those patients, 30 (46.9%) received bevacizumab in the first line (B1L), and 34 (53.1%) received it in the second line and beyond (B2L+). The average length of treatment with bevacizumab was 24.4 weeks (range: 0-232.7 weeks). The patterns of progression were categorized as local, distant, diffuse, multifocal, or multi-pattern. Results Local progression was seen in 46.7% of B1L patients and 26.5% of B2L+ patients, distant in 3.3% and 2.9%, diffuse in 20% and 47%, multifocal in 10% and 8.8%, and multi-pattern in 3.3% and 11.8%. No differences between the groups were observed for the distant (p = 0.3) or diffuse (p = 0.4) patterns. Grades 3 and 4 adverse events in the B1L and B2L+ groups were fatigue (33.3% vs. 17.6% respectively), hypertension (26.7% vs. 5.9%), thrombocytopenia (26.7% vs. 11.8%), neutropenia (26.7% vs. 11.8%), anemia (23.3% vs. 11.8%), leucopenia (20% vs. 8.8%), deep vein thrombosis (23.3% vs. 5.9%), seizure (16.7% vs. 8.8%), brain hemorrhage (6.7% vs. <1%), and delayed wound healing (6.7% vs. 2.9%). More total grades 3 and 4 adverse events occurred in the B1L group (p = 0.000519). Conclusions In our cohort, patterns of progression were not different in B1L and B2L+ patients. Moreover, both groups experienced similar adverse events, although more grades 3 and 4 events occurred in the B1L group, implying that severe adverse events in B1L patients could negatively affect survival outcomes. [ABSTRACT FROM AUTHOR]

Canine parvovirus 2 (CPV-2) was first identified in 1978, and is responsible for classic parvoviral enteritis. Despite the widespread vaccination of domestic carnivores, CPVs have remained important pathogens of domestic and wild carnivores. In this study, we isolated CPV-2 from Tibetan mastiffs and performed a global analysis of the complete VP2 gene sequences of CPV-2 strains in China. Six isolates were typed as new CPV-2a, according to key amino acid positions. On a phylogenetic tree, these six sequences formed a distinct clade. Five isolates occurred on the same branch as KF785794 from China and GQ379049 from Thailand; CPV-LS-ZA1 formed a separate subgroup with FJ435347 from China. One hundred ninety-eight sequences from various parts of China and the six sequences isolated here formed seven distinct clusters, indicating the high diversity of CPVs in China. Of 204 VP2 sequences, 183 (91.04%) encoded the mutation Ser297Ala, regardless of the antigenic type, implying that most Chinese CPV-2 strains contain the VP2 mutation Ser297Ala. However, the biological significance of this change from prototype CPV-2a/2b to new CPV-2a/2b types remains unclear. This study is the first to isolate new CPV-2a from the Tibetan mastiff. Our data show that new CPV-2a/2b variants are now circulating in China. [ABSTRACT FROM AUTHOR]

Astragali Radix (Huang-Qi) is a popular herbal medicine commonly used as a constituent in tonic herbal preparations. Hedysarum polybotrys Handel-Mazzetti is one species used of Astragali Radix. In this study, the immunomodulatory properties of H. polybotrys were explored by LPS-activated and SNP-treated RAW 264.7 cells and splenocytes and, daunoblastina-induced leucopenia BALB/c mice. Formononetin was used as the bioactive marker to monitor the quality of the H. polybotrys extracts. H. polybotrys was extracted with hot-water and methanol, and MeOH extract partitioned with H2O (M-H) and ethyl acetate (M-EA) to yield four different fractions. M-EA had the highest formononetin and total proanthocyanidin content and showed stronger inhibitory effects on the production and expression of NO, PGE2, iNOS and COX-2 in LPS-activated RAW 264.7 cells and splenocytes than the other fractions. In addition, M-EA significantly stimulated the proliferation of LPS-activated RAW 264.7 cells and splenocytes, enhanced NO radicals scavenging and attenuated NO-induced cytotoxicity. Furthermore, M-EA also significantly increased the rate of recovery of white blood cells level in daunoblastina-induced leucopenia mice. These evidences suggest that this traditional Qi-tonifying herb has potential effects in clinical conditions when immune-enhancing and anti-inflammatory effect is desired. [ABSTRACT FROM AUTHOR]

Digital morphology (DM) analyzers are widely applied in clinical practice. It is necessary to evaluate performances of DM analyzers by focusing on leukopenic samples. We evaluated the analytical performance, including precision, of a Sysmex DI-60 system (Sysmex, Kobe, Japan) on white blood cell (WBC) differentials in leukopenic samples. In a total of 40 peripheral blood smears divided into four groups according to WBC count (normal, mild, moderate, and severe leukopenia; each group n = 10), we evaluated precision of WBC preclassificaiton by DI-60. %coefficients of variation (%CVs) of precision varied for each sample and for each cell class; the fewer cells per slide, the higher %CV. The overall specificity and efficiency were high for all cell classes except plasma cells (95.9–99.9% and 90.0–99.4%, respectively). The largest absolute value of mean difference between DI-60 and manual count in each group was: 10.77, normal; 10.22, mild leukopenia; 19.09, moderate leukopenia; 47.74, severe leukopenia. This is the first study that evaluated the analytical performance of DI-60 on WBC differentials in leukopenic samples as the main subject. DI-60 showed significantly different performance depending on WBC count. DM analyzers should be evaluated separately in leukopenic samples, even if the overall performance was acceptable. [ABSTRACT FROM AUTHOR]

Simple Summary: Hematological toxicity may be a consistent issue in anal cancer patients undergoing concurrent chemo-radiation, with a potentially detrimental effect on clinical outcomes and patient compliance to treatment. Chemotherapy is the most important trigger, since it induces myelosuppression, but radiation dose delivered to the hematopoietically active bone marrow (BM) also plays an important role. Active bone marrow can be identified using functional imaging with 18-Fluoro-2-deoxy-glucose positron emission tomography (18FDG-PET) and selectively spared during radiation delivery via intensity-modulated radiotherapy (IMRT). We investigated, within a prospective phase II trial, the potential effectiveness of targeted avoidance of active BM comprised within pelvic bones in reducing the acute hematologic toxicity profile of anal cancer patients undergoing concomitant chemo-radiation for squamous cell carcinoma of the anus. The results of the first step of the study fulfilled the criteria to define BM-sparing IMRT as "promising" and to continue with the second step of the phase II trial. Purpose: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with 18FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. Methods: a one-armed two-stage Simon's design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0–G2 (vs. G3–G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the β = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0–G2 acute HT to further proceed with the trial. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. Results: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0–G2 events, way above the threshold set by the trial design. Conclusion: 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial. [ABSTRACT FROM AUTHOR]

Due to increasing resistance to commonly used antibiotics, the World Health Organization and Food and Drug Administration have advocated the development of new therapeutic regimens for Helicobacter pylori (H. pylori). This phase three, double-blind study (ERADICATE Hp) randomized (2:1) treatment-naïve adults with H. pylori infection and dyspepsia to RHB-105 (an all-in-one combination of omeprazole 40 mg, amoxicillin 1000 mg, and rifabutin 50 mg) or an identically-appearing placebo, both administered every 8 h for 14 days. The H. pylori eradication rate with RHB-105, using a modified intent-to-treat (mITT) population of subjects who received ≥1 dose of study drug and had test-of-eradication performed 28–35 days post-completion of therapy, was compared (one-sample Z-test) to a literature-derived comparator rate of 70% and success rate with physician-selected standard-of-care given to placebo failures. The mITT H. pylori eradication rate (95% CI) with RHB-105 of 89.4% (82.0–96.8%) was greater than both the literature-derived comparator rate (P < 0.001) and the standard-of-care rate of 63.0% (44.8–81.1%) (P = 0.006). Adverse events with an incidence ≥5% for RHB-105 were diarrhea (12.7%), headache (11.9%), chromaturia (9.3%), abdominal tenderness (6.8%), and dizziness (5.1%). No leukopenia was noted. RHB-105 (Talicia®) proved to be a safe and effective empiric therapy for H. pylori eradication. [ABSTRACT FROM AUTHOR]