Cryosurgery for Basal Cell Skin Cancer of the Head: 15 Years of Experience.

The clinical relevance of head and neck (H&N) tumors is related to the potential disfiguration of anatomical structures (by the tumor or surgical intervention), defining patients' individual features and emotional expression, loss or restraint of vital structures functions, and untoward socio-economic sequelae. This study is aimed to improve clinical outcomes of cryosurgery in patients with H&N basal cell skin cancer by refining the indications for cryosurgical treatment. In this study, cryosurgery was used in 234 patients with different stages of cutaneous basal cell carcinoma (BCC) of the head, including 101 patients with T1 tumors, 86-with T2, 5-T3, and 42 patients with tumors relapsing after failure of preceding various treatment modalities. Post-cryosurgery recurrence rate in patients with stage I BCC was 2.7%, with stage II tumors-5.6% and 34.9%-in patients with recurred tumors. Re-recurrence after cryoablation of recurrent tumors correlated with the tumor baseline size. The best aesthetic and long-term clinical results were documented in patients with lesions <1 cm in size with clear boundaries. Thus, cryosurgery is the method of choice for the majority of stage I basal cell carcinomas of the head. For patients with advanced and recurrent skin cancer, cryosurgery is relevant in rare cases selected according to refined indications.

Present and future projections of heatwave hazard-risk over India: A regional earth system model assessment.

The heatwave is a disastrous hazard having significant impacts on health and society. This study analyses the heatwave hazards and risk for India's current and future scenarios using socioeconomic vulnerability and temperature datasets during the summer (April-June) season. The Census of India (CoI) 2011 datasets were considered to assess current vulnerability and projected from the SocioEconomic Data And Application Center (SEDAC) population at Shared Socioeconomic Pathway (SSP) 4 for future vulnerability. Whereas IMD temperature data used for hazard assessment for the present scenario (1958-2005) while projected temperature data from regional earth system model REMO-OASIS-MPIOM (ROM) were used for the future (2006-2099) scenario. The study exhibited the most hazardous, vulnerable, and risk-prone regions identified as the south-eastern coast and Indo-Gangetic plains and some populous districts with metropolitan regions (Mumbai, Delhi, and Kolkata) under the current scenario. The coupled model ROM has efficiently captured the critical districts with higher and lower risk, showing its future projection capability. The study highlighted that the heatwave hazard-risk would significantly worsen in future scenarios in all districts under enhanced global warming and largely affecting the districts in the eastern and middle Indo-Gangetic plains and Malabar region. The present study will provide sufficient insights into designing mitigation strategies and future adaptive planning for the heatwave risk, which is one of the targets under Sustainable Development Goal 13 (Goal 13: Climate Action).

Rivaroxaban for the prevention of venous thromboembolism after radiofrequency ablation of saphenous veins concomitant with miniphlebectomy, sclerotherapy, or no treatment of varicose tributaries.

OBJECTIVE: To assess the efficacy and safety of once-daily 10 mg rivaroxaban for venous thromboembolism prophylaxis after ClosureFast radiofrequency ablation (RFA) of saphenous veins. METHOD: The medical records of patients, who had a Caprini score of ≥3, underwent RFA, received prophylactic rivaroxaban for five days, and completed follow up at one month were reviewed for efficacy (a combination of endovenous heat-induced thrombosis [EHIT] grade of 2-4, any symptomatic or asymptomatic deep vein thrombosis [DVT], and symptomatic pulmonary embolism [PE]) and safety (a combination of major and clinically relevant non-major [CRNM] bleeding) outcomes. RESULTS: The results of RFA for 248 great saphenous and 24 small saphenous veins with the concomitant miniphlebectomy (63.8%) and sclerotherapy (16.5%) were analyzed. The primary efficacy outcome occurred in 5 of 218 (2.3%; 95%CI, 1.0-5.3%) patients: three EHITs and two symptomatic DVTs. The CRNM bleeding was reported in two patients (0.9%; 95% CI, 0.2-3.3%). No difference was observed in comparison with 79 similar patients who received 40 mg of subcutaneous enoxaparin during the same time period. CONCLUSION: Once-daily 10 mg rivaroxaban is suitable for VTE prophylaxis after RFA of saphenous veins.

Cutaneomeningospinal Angiomatosis (Cobb Syndrome) in a Young Patient.

Cobb Syndrome (Spinal Arteriovenous Metameric Syndrome 1-31 (SAMS 1-31)) is a rare, non-hereditary disorder. Approximately 100 cases of CS have been described to date. The actual incidence may be much higher since only symptomatic patients were documented. In particular, post mortem studies suggest a possibly higher incidence of this syndrome. The main clinical manifestations of this syndrome include skin stains of vascular nature on the torso, in combination with spinal vascular malformations localized in one and the same metameric or spinal segment. A rare diagnosis of this syndrome in patients over 18 is probably related to the fact that the disease may be asymptomatic throughout a long period of time, while patients may tend to disregard the skin lesions. As a result, most publications on this pathology are based on separate case reports. Significant variability of clinical manifestations as well as prolonged progress of the disease often cause errors in diagnosis. What follows is a case report of a young patient with Cobb Syndrome, who was admitted to a regional vascular centre with a misdiagnosis of stroke. 20 patients of young age (from 20 to 35 years old), with a diagnosis of stroke, who were admitted to a University Clinic (of the Russian National Research Medical University Named After Pirogov N.I., Moscow). Among this group of patients, a patient with Cobb syndrome was identified. Patient P., of 22 years, presented with acute, intensive cervical spinal pain, predominantly on the right, numbness and weakness in the arms and legs. About 3 weeks before admission to the hospital, the patient had ARVI with a fever of up to 37.5°C: two weeks before the onset of symptoms, he had undergone extirpation of 2 teeth, for which reason he spent over 2 hours in a forced position with his head thrown back (prolonged overextension in the cervical spine). Multiple skin angiomas on the chest spreading to the shoulder and scapula region. Tetraparesis up to 4 points: tetraparesis in hands with low muscle tone, low reflexes, tetraparesis in legs with high muscle tone, high reflexes, foot clonus when causing Achilles reflexes, tremor in the extremities and no plantar reflex pathology were detected, sensitivity disorders in the hands "the high gloves" and no pelvic disorders were detected. Given the presence and exacerbation of neurological symptoms and cutaneous angiomas, MRI with a contrast agent of the cervical spine was recommended. MR-image of an advanced arteriovenous malformation (AVM) of the cervical spinal cord with signs of gliosis and spinal cord oedema at the C2-C7 level. Endovascular embolization of the AVM in the cervical spinal cord was performed. The treatment led to the complete reversal of neurological symptoms. In the presence of skin lesions, the diagnosis of CS does not present particular difficulties, so in children and young patients with skin angiomatosis, it is advisable to conduct a comprehensive examination using selective spinal angiography or MR angiography to exclude arteriovenous malformations in the spinal cord.

Respiratory syncytial virus upregulates IL-33 expression in mouse model of virus-induced inflammation exacerbation in OVA-sensitized mice and in asthmatic subjects.

BACKGROUND: Bronchial asthma (BA) is a chronic disease of the airways. The great majority of BA exacerbations are associated with respiratory viral infections. Recent findings point out a possible role of proinflammatory cytokine interleukin-33 (IL-33) in the development of atopic diseases. Although, little is known about the role of IL-33 in virus-induced BA exacerbations. METHODS: We used mouse models of RSV (respiratory syncytial virus)-induced inflammation exacerbation in OVA-sensitized mice and RSV infection alone in adult animals to characterize expression of il33 in the mouse lungs. Moreover, we studied the influence of il33 knockdown with intranasally administrated siRNA on the development of RSV-induced inflammation exacerbation. In addition, we evaluated the expression of IL33 in the ex vivo stimulated PBMCs from allergic asthma patients and healthy subjects with and without confirmed acute respiratory viral infection. RESULTS: Using mouse models, we found that infection with RSV drives enhanced il33 mRNA expression in the mouse lung. Treatment with anti-il33 siRNA diminishes airway inflammation in the lungs (we found a decrease in the number of inflammatory cells in the lungs and in the severity of histopathological alterations) of mice with RSV-induced inflammation exacerbation, but do not influence viral load. Elevated level of the IL33 mRNA was detected in ex vivo stimulated blood lymphocytes of allergic asthmatics infected with respiratory viruses. RSV and rhinovirus were the most detected viruses in volunteers with symptoms of respiratory infection. CONCLUSION: The present study provides additional evidence of the crucial role of the IL-33 in pathogenesis of RSV infection and virus-induced allergic bronchial asthma exacerbations.

M1-like macrophages are potent producers of anti-viral interferons and M1-associated marker-positive lung macrophages are decreased during rhinovirus-induced asthma exacerbations.

BACKGROUND: Macrophages (Mф) can be M1/M2 polarized by Th1/2 signals, respectively. M2-like Mф are thought to be important in asthma pathogenesis, and M1-like in anti-infective immunity, however their roles in virus-induced asthma exacerbations are unknown. Our objectives were (i) to assess polarised Mф phenotype responses to rhinovirus (RV) infection in vitro and (ii) to assess Mф phenotypes in healthy subjects and people with asthma before and during experimental RV infection in vivo. METHODS: We investigated characteristics of polarized/unpolarized human monocyte-derived Mф (MDM, from 3-6 independent donors) in vitro and evaluated frequencies of M1/M2-like bronchoalveolar lavage (BAL) Mф in experimental RV-induced asthma exacerbation in 7 healthy controls and 17 (at baseline) and 18 (at day 4 post infection) people with asthma. FINDINGS: We observed in vitro: M1-like but not M2-like or unpolarized MDM are potent producers of type I and III interferons in response to RV infection (P<0.0001), and M1-like are more resistant to RV infection (P<0.05); compared to M1-like, M2-like MDM constitutively produced higher levels of CCL22/MDC (P = 0.007) and CCL17/TARC (P<0.0001); RV-infected M1-like MDM were characterized as CD14+CD80+CD197+ (P = 0.002 vs M2-like, P<0.0001 vs unpolarized MDM). In vivo we found reduced percentages of M1-like CD14+CD80+CD197+ BAL Mф in asthma during experimental RV16 infection compared to baseline (P = 0.024). INTERPRETATION: Human M1-like BAL Mф are likely important contributors to anti-viral immunity and their numbers are reduced in patients with allergic asthma during RV-induced asthma exacerbations. This mechanism may be one explanation why RV-triggered clinical and pathologic outcomes are more severe in allergic patients than in healthy subjects. FUNDING: ERC FP7 Advanced grant 233015, MRC Centre Grant G1000758, Asthma UK grant 08-048, NIHR Biomedical Research Centre funding scheme, NIHR BRC Centre grant P26095, the Predicta FP7 Collaborative Project grant 260895, RSF grant 19-15-00272, Megagrant No 14.W03.31.0024.

The frequency and clinical significance of nontarget superficial and deep vein occlusion after physician compounded foam sclerotherapy of varicose tributaries.

OBJECTIVE: To evaluate the incidence and clinical relevance of silent nontarget occlusion (NTO) of superficial and deep veins occurring after ultrasound-guided foam sclerotherapy (UGFS) that can be detected by serial duplex ultrasound scan (DUS). METHODS: This retrospective analysis evaluated the medical records of patients treated with UGFS at a private clinic in Moscow, Russia from 2015 to 2017. All patients underwent serial DUS at 1 to 2 weeks and 1, 3, 6, and 12 months after UGFS. RESULTS: During the observation period, 268 patients were treated with UGFS, using physician compounded polidocanol foam 257 lower limbs of 196 patients (73%) with varicose veins who underwent DUS at 1 to 2 weeks after the last session of UGFS (inclusion time-point): 139 women and 57 men (mean age: 44.2 ± 12.2 years) with the following CEAP clinical class distribution: C2, 74.0%; C3, 20.0%; C4, 4.5%; and C5, 1.5%. NTO at the inclusion time-point occurred in 60 limbs (23.3%) of 57 patients (28.5%) and was symptomatic only in three limbs (1.2%). Most occlusions were localized in the untreated great saphenous vein trunk (n = 28) and the calf muscle veins (n = 23). Overall, 72%, 44%, 29%, and 10% of all limbs and 77%, 45%, 28%, and 12% of limbs with NTO were followed up by DUS at 1, 3, 6, and 12 months, respectively. There were no cases of thrombus progression or symptomatic venous thromboembolism (VTE). At six months, no deep vein occlusions persisted. CONCLUSIONS: The frequency of nontarget vein occlusion after UGFS revealed by serial DUS may be as high as 23.3%. These occlusions tend to resolve within six months and are not associated with symptomatic VTE.

Ultrashort ssDNA in Retinoblastoma Patients Blood Plasma Detected by a Novel High Resolution HPLC Technique: a Preliminary Report.

A significant population of ultrashort (50-150n) single-stranded DNA fragments were found in exosome-free blood plasma of retinoblastoma patients (6.84 ng mL-1), but not in plasma of healthy donors. An original high resolution HPLC technique has been proposed to reveal and characterize this peculiarity. To solve this task, a novel molecular size exclusion - anion exchange analytical technique was developed. Its applicability to diagnostics and oncogenesis research is quizzed here.

A novel peptide dendrimer LTP efficiently facilitates transfection of mammalian cells.

One of the urgent problems of gene therapy is the search for effective transfection methods. Synthetic cationic peptides (CPs) are considered to be one of the most promising approaches for intracellular transport of oligonucleotides. Almost unlimited possibilities of the architectural design of CPs (linear and cyclic structures with a variation of chirality as well as dendrimers) make CPs an effective tunable carrier in this field. Cationic peptide dendrimers (PDs), as a relatively new direction, have significant advantages as gene delivery vehicles by virtue of non-natural ε-amide bonds that significantly increase their resistance to proteolysis. Moreover they also possess much lower cytotoxicity than linear peptides, which is crucial for the potential clinical application of CPs. In a further development of oligonucleotide delivery systems, we have synthesized a collection of 14 CPs, including linear peptides, lipopeptides and PDs. Their activity was evaluated by transfection of 293T cells with plasmids containing reporter genes encoding luciferase or a green fluorescent protein. The obtained results demonstrated that the greatest activity was exhibited by PDs, particularly LTP, an arginine-rich peptide dendrimer, which possesses low cytotoxic and hemolytic activity. The peptide exhibited high cell-penetrating activity, confirmed by fast dissipation of the membrane potential of cells probed by dis-C3-(5). The quantitative analysis of labelled LTP in tissue samples of mice revealed that the Cy5-LTP/siRNA complexes have a reasonable tropism to lung tissues.

Retinoblastoma: Magnetic Isotope Effects Might Make a Difference in the Current Anti-Cancer Research Strategy.

Human retinoblastoma cells were proven to possess some very unusual DNApolß species. Being 23.5 kDa monomers, which itself is not common for the DNApolß superfamily members, these chromatin associated proteins manifests most of the DNApolß-specifc functional peculiarities making them legitimate targets for DNA repair cytostatic inhibitors. Particularly, these tumor specific enzymes were found to be very sensitive to 25Mg2+-, 43Ca2+- and 67Zn2+-promoted magnetic isotope effects (MIE) caused a marked DNA sequence growth limitation as well as a formation of the size-invalid, i.e. too short in length, DNA fragments, totally inappropriate for the DNA repair purpose. This MIE-DNApolß match may serve a starting point for further move towards the paramagnetic path in current developments of anti-cancer strategies.