Acetic acid disinfection as a potential adjunctive therapy for non-severe COVID-19.

PURPOSE: SARS-CoV-2 is a new pandemic influenza caused by a coronavirus which main route of transmission is through exhaled droplets that primarily infect the nose and the nasopharynx. The aim of this paper is to evaluate the effect of acetic acid, the active component of vinegar, as a potential disinfectant agent for upper airways. METHODS: Twenty-nine patients were enrolled and divided into two groups: group 1 (14 patients) was composed of patients treated with off-label hydroxychloroquine and lopinavir/ritonavir, whereas group 2 (15 patients) was composed of patients treated with hydroxychloroquine only, combined with the inhalation of acetic acid disinfectant at a 0.34% concentration. A questionnaire-based evaluation of symptoms was performed after 15 days in both groups. RESULTS: It appears that the number of patients treated with acetic acid (group 2) that experienced improvement in individual symptoms was double that of the other group of patients (group 1), although numbers are too small for robust statistical analysis. CONCLUSIONS: Considering its potential benefits and high availability, acetic acid disinfection appears to be a promising adjunctive therapy in cases of non-severe COVID-19 and deserves further investigation.

Postoperative long-term morbidity of extended endoscopic maxillectomy for inverted papilloma.

BACKGROUND: Extended endoscopic maxillectomy (Sturmann-Canfield procedure) allows full visualization of the maxillary sinus by sectioning the lacrimal duct and removing the medial part of the anterior maxillary wall. The aim of this study is to evaluate the morbidity of Sturmann-Canfield procedure in patients treated for inverted papilloma. METHODOLOGY: The clinical records of all patients treated with a Sturmann-Canfield procedure for inverted papilloma from October 2000 to September 2015 at two teaching hospitals were reviewed. All patients were evaluated by nasal endoscopy and lacrimal system patency was assessed. Pre-maxillary cutaneous sensitivity was tested with a Semmes-Weinstein aesthesiometer and thermic stimulation. The SNOT-22 questionnaire was administered. Patients were also asked to report any other post-surgical complaints. RESULTS: Fifty-nine patients were identified. Mean follow-up after surgery was 66.3 months. Mean SNOT-22 score was 5.94 (range 0-20); the majority of patients (86%) had a SNOT-22 symptom score of 3 or lower. Mucocoele occurred in 3 (5%) cases. Lacrimal pathway obstruction was observed in 7 (12%) patients. Fourteen (24%) patients complained of paraesthesia in the malar area; hypoesthesia was present in only 5 (8%) cases. Hypoesthesia in the region innervated by the anterior superior alveolar nerve was detected in 17 (29%) patients. One patient reported a slight depression of paralateronasal soft tissues. CONCLUSIONS: Although nasal function outcomes and the results from SNOT-22 questionnaires were favourable, a high rate of neurologic and lacrimal complications was observed. Potential morbidity of the intervention, including the possibility of negative aesthetic sequelae, should be discussed during preoperative counselling.

Video endoscopic oro-nasal visualisation of the anterior wall of maxillary sinus: a new technique.

The anterior wall of the maxillary sinus represents a blind spot in maxillary sinus endoscopic surgery because of the absence of proper visualisation and instrumentation to reach it. The aim of this study was to validate a new approach through the oral cavity into the nose with a flexible video endoscope (oro-nasal endoscopic approach; ONEA) to visualise the entire anterior maxillary wall including the anteromedial angle. We started from a dried bone cadaver model, and then dissected fresh-frozen cadavers. The maxillary sinus was explored with a rigid and a flexible endoscope entering from the nose. Next, a flexible endoscope was introduced through the mouth and back up through the choana, it accessed the maxillary middle antrostomy, entering inside the sinus and looking at the anterior wall. A small ruler inserted inside the sinus demonstrated all the angles visualised. The new ONEA technique allows complete visualisation of the anterior wall of the maxillary sinus with inspection of all blind spots. It is therefore possible to detect lesions that would normally not be visible with a normal rigid endoscope. We demonstrate the validity of a novel technique that allows visualisation of the infero-medial angle of the anterior wall of the maxillary sinus.

Endoscopic treatment of frontal sinus mucoceles with lateral extension.

To describe a new and useful criterion to identify endoscopically approachable lateral frontal sinus mucoceles. We retrospectively reviewed all patients diagnosed with frontal mucocele with lateral extension who underwent endoscopic sinus surgery (ESS) at the Department of Otorhinolaryngology, San Raffaele Scientific Institute over a 4 year period, from January 2008 to March 2012. We analyzed patient charts, pre- and post-operative imaging, operative reports, postoperative periods, and follow-up records. Our series is composed of seven patients, four males and three females, with a mean age of 56 years. Symptoms at presentation varied depending on the extent of mucocele growth and orbital and intracranial invasion. Mucocele extension medially to a virtual sagittal plane tangential to the medial side of the ocular globe was also evaluated with computed tomography, to determine the appropriateness and feasibility of an ESS procedure. After pre-operative investigations, patients underwent marsupialization of the mucocele with ESS. Postoperative follow-up ranged from 1 to 4 years. At present, all patients remain free of disease, as documented by radiological imaging. In defining endoscopically approachable lesions, it is essential to determine their extension beyond a virtual sagittal plane tangential to the medial side of the ocular globe. The success of the endoscopic procedures described was undoubtedly linked to the localization of the mucocele medial wall. This criterion is more important than the size of the mucocele, and accurate computed tomography evaluation can identify those mucoceles approachable with ESS, even if laterally extended.

Transcriptional profiles in melanocytes from clinically unaffected skin distinguish the neoplastic growth pattern in patients with melanoma.

BACKGROUND: It is generally accepted that sunlight may contribute to the development of melanoma. OBJECTIVES: To analyse gene expression of melanocytes obtained from clinically unaffected skin of patients with melanoma and healthy controls before and after exposure to ultraviolet B radiation. METHODS: Using GeneChip array technology, the gene expression of melanocytes obtained from the two donor groups was profiled, in order to identify transcriptional differences affecting susceptibility to melanoma. RESULTS: The data collected did not show any difference between the expression profiles of melanocytes purified from normal donors and from patients with melanoma that was able to give a statistically significant class separation. However, by means of unsupervised clustering our data could be divided into two main classes. The first class included the transcriptome profiles of melanocytes obtained from skin samples of patients with a vertical growth phase (VGP) melanoma, while the second class included the transcriptome profiles of melanocytes obtained from skin samples of patients with a radial growth phase (RGP) melanoma. CONCLUSIONS: These data suggest that melanocytes in patients with VGP and RGP melanomas show significant differences in gene expression profiles, which allow us to classify patients with melanoma also from clinically unaffected skin.

New thymidylate synthase inhibitors induce apoptosis in melanoma cell lines.

Malignant melanoma is particularly resistant to conventional chemotherapy and radiotherapy. For this reason in the past years a huge variety of new compounds has been developed with potential chemotherapeutic activity which needs to be tested in vitro and in vivo. We investigated the in vitro action of three new experimental antifolate substances (MR7, MR21 and MR36) with a critical target for thymidylate synthase (TS), an essential enzyme for DNA synthesis. The response of two melanoma cell lines (SK-MEL-2 derived from malignant melanoma metastasis and SK-MEL-28 derived from primary malignant melanoma) was examined after treatment with these substances. The antifolate agents induced apoptosis in SK-MEL-2 and SK-MEL-28 cells as confirmed by the TUNEL technique and Comet Assay. Western-blot analysis showed a down-regulation of Bcl-2 protein level and PARP cleavage, otherwise p53 and Bax expressions were not modulated. Moreover, these antifolate-induced apoptosis was accompanied by both pro-caspase-9 and -8 activations. These results were supported by the use of the pan-caspases inhibitor Z-VAD-FMK that almost completely decreased the amount of apoptosis in both the melanoma cell lines treated with antifolate. In conclusion our results show that TS inhibitors are able to induce apoptosis through a caspase-mediated pathway, but without the involvement of the p53/Bax signalling.

Hypertension in early alcohol withdrawal in chronic alcoholics.

AIMS: Hypertension is an established risk factor in chronic alcoholics, but little is known about the relationship between blood pressure (BP), severity of their alcohol abuse, and severity of alcohol withdrawal syndrome (AWS). METHOD: BP was assessed daily for 18 days in a series of chronic alcoholics on early alcohol withdrawal (AW), while also assessing the severity of their AWS on the CIWA-Ar scale. RESULTS: A sharp and sustained decrease in BP was observed after AW; at T0, BP had increased in 55% of patients, and at T18 in 21%. The variation of BP is partially explained by years of at-risk drinking and AWS severity, but other factors may play a role in hypertension in alcoholics, as a large amount of BP variation was not explained by the alcohol-abuse-related parameters that we studied. BP values were not correlated with cigarette smoking, anxiety, or depression. Hypertension found in 'detoxified' alcoholics (approximately 20%) may be related to alcohol-independent hypertension or to a long-lasting alcohol-induced derangement of the BP regulating mechanisms. Further research is needed in these patients to elucidate the mechanisms of persistent hypertension and to set up a treatment protocol. At present, careful monitoring is advisable, as well as pharmacological treatment for moderate or severe hypertension; often a modification of life-style is needed which includes physical activity and possibly sodium (Na) restriction, since hypertension in detoxified alcoholics seems to be Na sensitive. CONCLUSION: Complete alcohol abstinence must be recommended to all hypertensive alcoholics, as AW-induced transient hypertension was found to be harmless in all our subjects, and abstinence leads to a complete recovery from hypertension in most cases.

Decrease in toxic potential of mixed tensides maintained below the critical micelle concentration: an in vitro study.

Sodium lauryl sulphate (SLS) is an anionic tenside widely utilized in commercial topical preparations that may cause skin irritation. It has been shown that the barrier damage caused by SLS in vivo is lower when SLS is used in combination with other tensides which are able to reduce the critical micelle concentration (CMC). The aim of our study was to evaluate if the cytotoxic effect of SLS is reduced by the association with different tensides also at concentrations well below the CMC. Normal human keratinocytes from plastic surgery were grown in serum-free medium. At subconfluency, the cells were treated with SLS at a dose of 0.0025% in combination with cocamidopropyl betaine, Tween 20 and Tween 80 at the minimum toxic dose. Following tenside treatment, the culture medium was changed, and after 24 h the cells were collected for (3)H-thymidine incorporation, the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay and neutral red (NR) uptake. The cytotoxic effect on normal human keratinocytes, as evaluated by (3)H-thymidine incorporation, MTT assay and NR uptake, was significantly decreased by the combination with all the tested tensides. The correlation between cytotoxicity and physical properties was also studied by a conductimetric assay to investigate the mechanism involved in this toxicity reduction.

Ultraviolet B radiation induces activation of neutral and acidic sphingomyelinases and ceramide generation in cultured normal human keratinocytes.

The sphingomyelin pathway is an ubiquitous, evolutionary conserved signaling system which transduces an extracellular signal into the cell. During the past few years increasing evidence has shown that the sphingolipid ceramide may play a role as a second messenger in intracellular signal transduction. The ceramide generation via sphingomyelinase (SMase) is followed by three major cellular responses: cell growth arrest, induction of cell differentiation and/or induction of programmed cell death or apoptosis. The aim of this study is to investigate whether activation of SMases and generation of ceramide can be induced by UVB radiation in normal human keratinocytes. The present data show that exposure to UVB radiation results in rapid generation of ceramide. The ceramide accumulation starts 15 min after UV exposure and progressively increases up to 24 h. In vitro measurement of SMase activity following exposure to UVB evidences an activation of both neutral and acidic SMases. Moreover, UVB induces apoptosis in normal human keratinocytes as shown by TUNEL technique and FACS analysis. These data indicate that UVB induced ceramide generation and activation of both neutral and acidic SMases, suggesting that sphingolipids metabolism may be involved in the UVB signaling pathway.

A case of Sweet's syndrome associated with monoclonal immunoglobulin of IgG-lambada type and p-ANCA positivity.

We report a case of Sweet's syndrome associated with monoclonal gammopathy of uncertain significance (MGUS) and positivity for perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). A 65-year-old man patient came to our hospital complaining of remittent-intermittent fever, weight loss, associated with papules affecting all his body and without mucosal or ocular involvement. Histology of biopsy specimens of papules allowed the diagnosis of Sweet's syndrome. This is the first case of this rare syndrome associated both with MGUS and p-ANCA positivity. The monoclonal immunoglobulin, possibly directed to neutrophils like an antibody, may cause both their fragmentation and release of antigens responsible of p-ANCA appearance.

[Non-traumatic rhabdomyolysis: clinical and laboratory diagnosis, assessment of renal complications]. / La rabdomiolisi non traumatica: riconoscimento clinico e di laboratorio, valutazione delle complicanze renali.

PURPOSE: Non traumatic rhabdomyolysis (RML) is an infrequent and sometimes clinically silent syndrome. RML incidence is increasing in the last few years. A prospective study was performed: 1) to value the non traumatic RML incidence in patients admitted to Emergency Room; 2) to reevaluate the clinical and laboratory criteria of diagnosis; 3) to establish complications' incidence and prognosis during the recovery. PATIENTS AND METHODS: In Emergency Medical First Aid 15.301 patients were examined. To the study were admitted only patients having CK level grater than fivefold the upper normal limits and without trauma, recent surgery, heart and cerebral disease. RESULTS: During the six months study, non traumatic RML incidence was 0.1% (16 patients of 15.301). Drugs, alcohol and substance abuse acute intoxication were the commonest causes. The Acute Renal Failure (ARF) was the more frequent complication (9 patients of 16). Four patients of nine was treated only by fluid administration, the other five by dialysis. Oligoanuric-ARF appeared only in patients affected by toxic RML. These patients had no-return to normal renal functional values at the time of hospital discharge. CONCLUSIONS: Non traumatic RML should be take into account by emergency doctor in cases of acute intoxication. To prevent the complications it's necessary the right interpretation of clinical and laboratory datas and an early and adequate therapy.

Delayed ANCA positivity in pulmonary-renal syndrome.

A 57-year-old man was admitted due to rapidly progressive renal failure and pulmonary edema. Chest X-ray showed a bilateral lung infiltrate, while a normal myocardial contractility was reported by echocardiography. Though initially ANCA were absent, a necrotizing vasculitis with polymorphonuclear leukocyte infiltrate was observed in a kidney biopsy specimen. Renal histology was compatible with microscopic polyangiitis because of necrotizing lesions located at small vessels and at glomeruli that were not crescentic. Corticosteroids and immunosuppressive treatment was played with significant clinical improvement. Six months later, the patient died of a gastrointestinal hemorrhage due to bowel perforation by vasculitic lesion. This time high p-ANCA positivity was detected and at renal histology crescentic glomeruli were observed.

In vitro testing of tensides employing monolayer cultures: a comparison with results of patch tests on human volunteers.

Evaluation of the irritant potential of new products or ingredients prior to human testing is generally performed in vivo on animals. However, according to the 6th amendment and following updates of the European Community directive on cosmetic products (93/35/EEC), animal testing will be banned when suitable substitutes will be available. To know whether in vitro tests for assessment of skin irritancy provide results approaching human conditions, comparisons have to be made between data deriving from in vitro tests and skin response in humans. The aim of our study was to assess the validity of the monolayer culture system of normal human keratinocytes as a model for the evaluation of the irritant effects of detergents, by comparing in vitro cell culture data to in vivo acute skin irritancy effects of cocamidopropyl betaine (CAPB), an amphoteric compound, Tween 20 (TW20) (polysorbate 20) and Tween 80 (TW80) (polysorbate 80), representing nonionic compounds, applied to the skin of 24 healthy volunteers at a concentration similar to that employed in commercial products. As parameters for cytotoxicity, cell proliferation, cell membrane integrity and cell metabolism were assessed by cell counts, thymidine incorporation, MTT conversion, and Neutral Red uptake. In order to increase the sensitivity of the in vivo evaluation, bioengineering methods for assessment of the effects of test products on the skin were employed. Whereas all 4 in vitro methods ranked the tensides according to their toxicity in the following order: CAPB>SLS>TW20>TW80, both in vivo methods agreed in identifying SLS as the most irritating substance. Moreover, as compared with the irritation potential on human skin, all 4 in vitro tests overestimated the toxicity of CAPB. This suggests that the keratinocyte monolayer cell culture technique cannot directly replace in vivo methods, and that data obtained by this method should be interpreted cautiously.

Effect of selective enzymatic digestions on skin biopsies from pseudoxanthoma elasticum: an ultrastructural study.

Skin biopsies from patients with pseudoxanthoma elasticum (PXE) were studied by electron microscopy either before or after selective digestions with collagenase, elastase, trypsin, hyaluronidase, chondroitinase AC and ABC, with the aim of identifying an eventual organic component associated with mineralization within the elastin fibers and the chemical nature of the enormous aggregates of filaments very often associated with, but distinct from mineralized elastin fibers. The results obtained, on both embedded thin sections and fresh tissue fragments, showed that elastin fibers, whether mineralized or not, were sensitive only to elastase, and they did not contain significant amounts of materials different from elastin that could be accounted for by ion precipitation; the aggregates of microfilaments in strict connection with altered elastin fibers were mostly sensitive to elastase and hyaluronidase, were partially removed by trypsin and chondroitinase, and were not modified by collagenase, which seems to indicate that the microfilaments consist mainly of abnormally aggregated elastin molecules together with low sulfated proteoglycans. It may be concluded that PXE is a complex genetic disorder of the connective tissue, and that mineralization of elastin is only one of the alterations of the extracellular matrix.