MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms

Journal of Neurology - Despite olfactory disorders being among the most common neurological complications of coronavirus disease 2019 (COVID-19), their pathogenesis has not been fully elucidated...     

Urine testing to monitor adherence to TB preventive therapy

This study examined the validity of the Arkansas urine test. One hundred ninety-four adolescents submitted an unannounced urine specimen monthly (for 6 to 8 months). Duplicate specimens were blindly tested with high agreement (kappa >90%). Sensitivity and specificity were estimated. In 68% of test runs, adolescents recalled taking INH within 24 hr of specimen collection. For recall intervals of 24, 48, and 72 hr, sensitivity was 87, 85, and 83%, respectively. Females were less likely to test positive when INH was taken within the previous 24 hr (sensitivity 84 versus 92% males). Specificity was 57, 91, and 95% at 24, 48, and 72 hr, respectively. The Arkansas urine test was practical to use, and results correlated well with self-reported adherence to INH for treatment of latent tuberculosis infection (LTBI), over several months of follow-up. The test may be useful as part of an adherence-monitoring program when used in conjunction with self-reported measures.     

Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention

The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance and metastasis. The expression of this pathway is frequently altered in breast cancer due to mutations at or aberrant expression of: HER2, ERalpha, BRCA1, BRCA2, EGFR1, PIK3CA, PTEN, TP53, RB as well as other oncogenes and tumor suppressor genes. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway and upstream HER2 has been associated with breast cancer initiating cells (CICs) and in some cases resistance to treatment. The anti-diabetes drug metformin can suppress the growth of breast CICs and herceptin-resistant HER2+ cells. This review will discuss the importance of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway primarily in breast cancer but will also include relevant examples from other cancer types. The targeting of this pathway will be discussed as well as clinical trials with novel small molecule inhibitors. The targeting of the hormone receptor, HER2 and EGFR1 in breast cancer will be reviewed in association with suppression of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway.     

The Evolving Scenario of Non‐AIDS‐Defining Cancers: Challenges and Opportunities of Care

Background.

The impact of highly active antiretroviral therapies (HAART) on the risk of non-AIDS-defining cancers (NADCs) and the role of biological and clinical factors in their pathogenesis are debated issues. The purpose of this review is to examine the epidemiology, etiology, and not-yet-defined pathogenic characteristics of NADCs and discuss topics such as treatment strategies, comorbidity, and multidrug interactions. Four types of NADCs that deserve special attention are examined: anal cancer, Hodgkin lymphoma (HL), hepatocellular carcinoma, and lung cancer.

Methods.

The PubMed database and the Cochrane Library were searched by focusing on NADCs and on the association among NADCs, HAART, aging, and/or chronic inflammation. All articles were reviewed to identify those reporting variables of interest.

Results.

NADC incidence is twofold higher in patients with HIV/AIDS than in the corresponding general population, and this elevated risk persists despite the use of HAART. The mechanisms that HIV may use to promote the development of NADCs are presently unclear; immunological mechanisms, either immunodeficiency and/or immunoactivation, may play a role.

Conclusion.

Recent clinical studies have suggested that equivalent antineoplastic treatment is feasible and outcome can be similar in HIV-infected patients on HAART compared with uninfected patients for the treatment of HL and anal and lung cancers. However, patients with advanced HIV disease and/or aging-related comorbidities are likely to experience worse outcomes and have poorer tolerance of therapy compared with those with less advanced HIV disease.     

The role of ultrasound and ultrasound-guided fine needle aspiration biopsy of lymph nodes in patients with skin tumours

Background

The primary aim of this study was to evaluate the diagnostic accuracy of ultrasound (US) in the study of superficial lymph nodes during the follow-up of patients surgically treated for skin tumours. The secondary objective was to compare positive cytological results with histological reports.

Patients and methods

From 2004 to 2011, 480 patients (male/female: 285/195; median age 57 years; prevalent skin tumour: melanoma) underwent US-guided fine-needle aspiration biopsy (FNAB) of suspicious recurrent lymph nodes. An expert radiologist first performed US testing of the lymph nodes, expressing either a negative or positive outcome of the test. Subsequently, US-guided FNAB was performed. FNAB positive patients were subjected to lymphadenectomy; the patients who tested negative underwent the follow-up.

Results

The size of lymph nodes was ≤ 2 cm in 90% of cases. Out of the 336 (70%) US “positive” patients, 231 (68.8%) were FNAB positives. Out of the 144 (30%) US “negatives”, 132 (91.7%) were FNAB negatives. The sensitivity and specificity of the US were 95% and 55.7%, respectively; the negative predictive value was 91.7% and the positive predictive value was 68.8%. Definitive histological results confirmed FNAB positivity in 97.5% of lymphadenectomies.

Conclusions

US is a sensitive method in the evaluation of superficial lymph nodes during the follow-up of patients with skin tumours. High positive predictive value of cytology was confirmed.     

The NF-κB inhibitor DHMEQ decreases survival factors,overcomes the protective activity of microenvironment and synergizes with chemotherapy agents in classical Hodgkin lymphoma

The NF-κB inhibitor DHMEQ has shown preclinical activity in classical Hodgkin Lymphoma (cHL).     

HF ultrasound vs PET-CT and telethermography in the diagnosis of In-transit metastases from melanoma: a prospective study and review of the literature

Background

Over the past several years the incidence of cutaneous melanoma has rapidly increased. This tumor develops often in-transit metastases that significantly reduce patient survival at 5 years. To improve prognosis and quality of life in patients with melanoma metastases, a mini invasive procedure like electrochemotherapy (ECT) is adopted to remove superficial tissue lesions. To detect the melanoma metastases, high frequency (HF) ultrasound (US) is used. This technique, though, can be time-consuming and it needs an expert operator and a high performing machine. Therefore, we asked whether the US could be replaced or integrated with other less time-consuming techniques such as 18-FDG positron emission tomography/computed tomography (PET-CT) and telethermography (TT).

Methods

Fifteen patients (4 males and 11 females - age range: 63–91) affected whit advanced stage melanoma were enrolled. They presented 52 in-transit metastases as detected by the three techniques used, HF-US, PET/CT and TT within 30 days before ECT.

Results

All the 52 lesions were detected by HF-US (100%), 24/52 were detected by PET-CT (42,6%) and 15/52 were detected by TT (27,7%). PET-CT reported 3.7% false positives, while no false positive were reported by TT.

Conclusions

As US detected 100% lesions, compared to the other two techniques used, US, along with clinical examination, has still to be considered as gold standard in the diagnosis of metastatic lesions. US, associated with an exhaustive anamnesis and accurate clinical examination, cannot be replaced by either PET-CT or TT. When US performing devices and experienced operators are not available, though, it is highly recommended to integrate US with at least one of the other techniques. Under certain circumstances, as in the case of obese and non-collaborating patients or in patients with lymphatic stasis, these techniques should be integrated to obtain exact in-transit metastases evaluation.     

Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype with mental retardation,episodic ataxia,and absences

Heterozygous mutations of PRRT2, which encodes proline‐rich transmembrane protein 2, are associated with heterogeneous phenotypes including benign familial infantile seizures (BFIS), or familial paroxysmal kinesigenic dystonia (PKD). We report a consanguineous Italian family with BFIS/PKD phenotype that contained 14 living members with 6 affected individuals (four men, ranging in age from 6–44 years). We identified the reported c.649dupC (p.Arg217ProfsX8) mutation of PRRT2 gene that cosegregated with the disease and was not observed in 100 controls of matched ancestry. Four patients with BFIS phenotype were heterozygous for this mutation, including the consanguineous parents of the two affected brothers with more severe phenotypes of BFIS/PKD—mental retardation, episodic ataxia, and absences—who were the only individuals to carry a homozygous c.649dupC mutation. This family provides strong evidence that homozygous PRRT2 mutations give rise to more severe clinical disease of mental retardation, episodic ataxia, and absences, and, thus, enlarges the clinical spectrum related to PRRT2 mutations. Moreover, it suggests an additive effect of double dose of the genetic mutation and underscores the complexity of the phenotypic consequences of mutations in this gene.     

Frontal assessment battery scores and non-motor symptoms in parkinsonian disorders

Using data from the PRIAMO study, we investigated non-motor symptoms (NMS) versus frontal lobe dysfunction in patients with idiopathic Parkinson disease (PD); 808 patients with PD and 118 with atypical parkinsonisms (AP) were consecutively enrolled at 55 Centers in Italy. Twelve categories of NMS were investigated. Cognitive impairment was defined as a Mini-Mental Status Evaluation score ≤ 23.8 and frontal lobe dysfunction as a Frontal Assessment Battery (FAB) score ≤ 3.48. Multivariable logistic regression was used to identify predictor of frontal lobe dysfunction in 524 PD patients, and a generalized linear model was used for each of the six FAB items. Not only the total FAB scores but also the single FAB items were lower in AP versus PD (p ≤ 0.005). Age (OR = 1.05), cognitive impairment (OR = 9.54), lack of cardiovascular symptoms (OR = 3.25), attention or memory problems (OR = 0.59) and treatment with L: -DOPA (OR = 5.58) were predictors of frontal lobe dysfunction. MMSE was negatively associated with all FAB items (β ≤ -0.16) and age with all FAB items but prehension behavior (β ≤ -0.01). Previous use of L: -DOPA was negatively associated with verbal fluency (β = -0.32) possibly acting as surrogate marker of disease duration. Cognitive impairment is a predictor of frontal lobe dysfunction. Among NMS, lack of attention or memory problems were negatively associated with frontal impairment. Further studies are nonetheless needed to better identify the predictors of frontal impairment in PD patients.