Wide Excision in Hidradenitis Suppurativa. Does it Modify the Course of Disease?

There is a lack of studies assessing whether wide excision surgery in hidradenitis suppurativa affected areas is useful for the global control of the hidradenitis suppurativa. We aimed to find whether surgery results were a better global control on the disease activity in both, the area where the surgery is performed and distant areas. We evaluated the disease course of 17 patients with hidradenitis suppurativa who underwent wide excision of complex fistula tracts between October 2018 and January 2022 at the Hospital Universitario de la Princesa, Madrid. We found that wide excision of complex fistulas produces an overall positive effect on the inflammatory activity in hidradenitis suppurativa that may be important to achieve an adequate control of the disease.

KEAP1-driven co-mutations in lung adenocarcinoma unresponsive to immunotherapy despite high tumor mutational burden.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated significant overall survival (OS) benefit in lung adenocarcinoma (LUAD). Nevertheless, a remarkable interpatient heterogeneity characterizes immunotherapy efficacy, regardless of programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB). KEAP1 mutations are associated with shorter survival in LUAD patients receiving chemotherapy. We hypothesized that the pattern of KEAP1 co-mutations and mutual exclusivity may identify LUAD patients unresponsive to immunotherapy. PATIENTS AND METHODS: KEAP1 mutational co-occurrences and somatic interactions were studied in the whole MSKCC LUAD dataset. The impact of coexisting alterations on survival outcomes in ICI-treated LUAD patients was verified in the randomized phase II/III POPLAR/OAK trials (blood-based sequencing, bNGS cohort, N = 253). Three tissue-based sequencing studies (Rome, MSKCC and DFCI) were used for independent validation (tNGS cohort, N = 289). Immunogenomic features were analyzed using The Cancer Genome Atlas (TCGA) LUAD study. RESULTS: On the basis of KEAP1 mutational co-occurrences, we identified four genes potentially associated with reduced efficacy of immunotherapy (KEAP1, PBRM1, SMARCA4 and STK11). Independent of the nature of co-occurring alterations, tumors with coexisting mutations (CoMut) had inferior survival as compared with single-mutant (SM) and wild-type (WT) tumors (bNGS cohort: CoMut versus SM log-rank P = 0.048, CoMut versus WT log-rank P < 0.001; tNGS cohort: CoMut versus SM log-rank P = 0.037, CoMut versus WT log-rank P = 0.006). The CoMut subset harbored higher TMB than the WT disease and the adverse significance of coexisting alterations was maintained in LUAD with high TMB. Significant immunogenomic differences were observed between the CoMut and WT groups in terms of core immune signatures, T-cell receptor repertoire, T helper cell signatures and immunomodulatory genes. CONCLUSIONS: This study indicates that coexisting alterations in a limited set of genes characterize a subset of LUAD unresponsive to immunotherapy and with high TMB. An immune-cold microenvironment may account for the clinical course of the disease.

Assessing upper limb function in multiple sclerosis using an engineered glove.

BACKGROUND AND PURPOSE: The importance of upper limb function in multiple sclerosis (MS) is increasingly recognized, especially for the evaluation of patients with progressive MS with reduced mobility. Two sensor-engineered gloves, able to measure quantitatively the timing of finger opposition movements, were previously used to assess upper limb disability in MS. The aims of the present study were: (1) to confirm the association between glove-derived variables and standard measures of MS disability in a larger cohort; (2) to assess the correlation with quantitative magnetic resonance imaging (MRI) and quality of life (QoL) measures; and (3) to determine if the glove-derived variables offer advantages over the standard measure for assessing upper limb function in MS, namely, the Nine-Hole Peg Test (9HPT). METHODS: Sixty-five patients with MS, stable on disease-modifying treatment, were evaluated at baseline using the glove, and through clinical examination (Expanded Disability Status Scale, Symbol Digit Modalities Test, Timed 25-Foot Walk Test and 9HPT), MRI evaluation and QoL questionnaires. Correlations between the glove-derived variables and clinical, MRI and QoL variables were assessed using Spearman's rank correlation coefficient analysis. RESULTS: Glove-derived variables significantly differed between patients with relapsing-remitting and those with progressive MS, with similar or slightly higher correlations of the 9HPT with clinical variables. We found greater correlations of the QoL physical component with glove-derived variables than with the 9HPT, and a significant correlation of its mental component with the glove-derived variables but not with the 9HPT. CONCLUSION: The study results, confirming previous findings and showing advantages over the 9HPT, encourage the investigation of sensitivity to change in glove-derived variables in a longitudinal setting.

Is it possible to use autologous adipose graft for wound repair in patients with coagulation disorders?

INTRODUCTION: Wound healing is an intricate process whereby the skin repairs itself after injury according to a specific sequence: haemostasis, inflammation, proliferation and remodelling. Cell therapy has the potential to improve wound healing conditions and can be applied in both acute and chronic wounds. Normal healing requires adequate haemostatic function. Patients with coagulation disorders whose haemostatic function is altered may not heal naturally. AIM: The aim of this study was to show a simple, safe and inexpensive minimally invasive technique for wound repair in patients with coagulation disorders which involves the use of concentrated autologous adipose cells. PATIENTS AND METHOD: Six patients were enrolled in this study at the Foundation of Haemophilia, in Buenos Aires, Argentina. Five patients had severe haemophilia type A and one had severe von Willebrand diseases. The average age was 37.5 years old. One patient had a retractile scar (RS) and five patients had cutaneous fistulas (CF). Suction was used to obtain autologous adipose graft from subcutaneous abdominal tissue. The graft was centrifuged and, the adipose cell concentrate was transferred to a syringe and injected in the edge of the lesion. RESULTS: One adipose suction in each patient was performed. There were no intraoperative or postoperative complications in any of the six patients. CONCLUSIONS: The application of autologous adipose graft is a simple and safe treatment for complicated wound repair in patients with coagulation disorders.

X-Linked Hereditary Nephropathy in Navasota Dogs: Clinical Pathology, Morphology, and Gene Expression During Disease Progression.

X-linked hereditary nephropathy (XLHN) in Navasota dogs is a spontaneously occurring disease caused by a mutation resulting in defective production of type IV collagen and juvenile-onset renal failure. The study was aimed at examining the evolution of renal damage and the expression of selected molecules potentially involved in the pathogenesis of XLHN. Clinical data and renal samples were obtained in 10 XLHN male dogs and 5 controls at 4 (T0), 6 (T1), and 9 (T2) months of age. Glomerular and tubulointerstitial lesions were scored by light microscopy, and the expression of 21 molecules was investigated by quantitative real-time polymerase chain reaction with selected proteins evaluated by immunohistochemistry. No significant histologic lesions or clinicopathologic abnormalities were identified in controls at any time-point. XLHN dogs had progressive proteinuria starting at T0. At T1, XLHN dogs had a mesangioproliferative glomerulopathy with glomerular loss, tubular necrosis, and interstitial fibrosis. At T2, glomerular and tubulointerstitial lesions were more severe, particularly glomerular loss, interstitial fibrosis, and inflammation. At T0, transforming growth factor ß, connective tissue growth factor, and platelet-derived growth factor α mRNA were overexpressed in XLHN dogs compared with controls. Clusterin and TIMP1 transcripts were upregulated in later stages of the disease. Transforming growth factor ß, connective tissue growth factor, and platelet-derived growth factor α should be considered as key players in the initial events of XHLN. Clusterin and TIMP1 appear to be more associated with the progression rather than initiation of tubulointerstitial damage in chronic renal disease.

Paraneoplastic pemphigus with eosinophilic spongiosis and autoantibodies against desmocollins 2 and 3.

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease associated with neoplasms, typically lymphoproliferative disorders. PNP is characterized clinically by painful erosive stomatitis and polymorphous skin lesions. Histopathological findings are also very varied, and include lichen planus-like and pemphigus-like changes. These polymorphic clinicopathological findings are probably due to the complex pathogenic mechanism, in which both cellular and humoral immunity are implicated. Eosinophilic spongiosis, although infrequent, can be found with pemphigus herpetiformis and bullous pemphigoid, although this association has not been established in PNP. The presence of autoantibodies against envoplakin and periplakin in PNP has been reported, but autoantibodies against desmocollins (Dscs) have been found in only a very few cases of PNP, probably due to the lack of studies on such associations. We report the first case, to our knowledge, of PNP with eosinophilic spongiosis as the initial histopathological finding, and presence of autoantibodies to Dsc2 and Dsc3.

The relationship between tumour necrosis factor (TNF)-α promoter and IL12B/IL-23R genes polymorphisms and the efficacy of anti-TNF-α therapy in psoriasis: a case-control study.

BACKGROUND: Antitumour necrosis factor (anti-TNF)-α agents can be used successfully to treat patients with psoriasis and other inflammatory diseases. However, very few studies have examined the relationship between TNF-α polymorphisms and the response to anti-TNF-α agents. OBJECTIVES: To study the association of single nucleotide polymorphisms (SNPs) of the TNF-α promoter and IL12B/IL23R genes with the response to anti-TNF-α in patients with psoriasis. METHODS: SNPs for the TNF-α promoter and IL12B/IL23R genes, and the presence of the HLA-Cw6 haplotype were genotyped for 109 patients. We studied the association between these SNPs and the efficacy of treatment at 3 and 6 months [Psoriasis Area and Severity Index (PASI) and body surface area (BSA)]. RESULTS: Patients with the TNF-α-238GG genotype more frequently achieved a PASI75 at 6 months (82·5% vs. 58·8%, P = 0·049). At 6 months, patients with the TNF-α-857CT/TT genotypes showed greater improvements in PASI score and BSA (83·1% vs. 92·7%, P = 0·004; 82·7% vs. 92·6%, P = 0·009) and more frequently achieved PASI75 (71·4% vs. 96·3%, P = 0·006). More patients with the TNF-α-1031TT genotype achieved PASI75 at 3 months (90·8 vs. 75·7, P = 0·047) and 6 months (85·5% vs. 65·7%, P = 0·038) and demonstrated superior improvements in PASI at 6 months (89·9% vs. 78·7%, P = 0·041). Patients with the IL23R-GG genotype (rs11209026) achieved PASI90 at 6 months more frequently (66·3% vs. 0, P = 0·006) and the improvement of the PASI score was also greater (86·8% vs. 67·8%, P = 0·013). Patients with the HLA-Cw6 haplotype showed poorer response than those without this haplotype. CONCLUSION: This study identified a relationship between certain TNF-α and IL12B/IL23R polymorphisms and the short-term response to anti-TNF-α drugs. If these results are confirmed, this information will allow for stratified consent with more accurate prediction of response/personalized choice of treatment hierarchy for the patient.

Coexistence of marginal zone cutaneous B-cell lymphoma and classic Hodgkin disease: does a biological relationship exist?

The coexistence of non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) in the same patient, although previously reported, is very unusual. This situation is extremely rare when the first diagnosis is a cutaneous B NHL, and exceptional if there is no personal background of cytostatic treatment. We report a 44-year-old man who developed cutaneous nodules over a period of two years. A marginal zone cutaneous B-cell lymphoma was diagnosed. On staging investigation a mass in the lingual tonsil was found and excision biopsy showed a classical Hodgkin lymphoma.

Light and electron microscopic analysis of consecutive renal biopsy specimens from leishmania-seropositive dogs.

Canine visceral leishmaniasis frequently causes renal damage that leads to chronic kidney disease. Fifteen dogs seropositive for Leishmania were selected and biopsied before (T0) and 60 days later after (T1) treatment with a specific anti-Leishmania pharmacological agent. Various parameters were selected for evaluating the glomerular and tubulointerstitial damage. At T0, mesangioproliferative and membranoproliferative glomerulonephritis were observed in 6 dogs, chronic glomerulosclerosis in 5, and end-stage kidney in 3; renal tissue from 1 dog was within normal histologic limits. The most frequently observed ultrastructural changes were foot-process effacement, thickening of the basement membranes, and immune deposits. One dog had mesangial immune deposits at T1 that had not been present at T0, so the diagnosis was changed to mesangioproliferative glomerulonephritis. In dogs with end-stage kidney, the number of obsolescent glomeruli and cystic atrophied glomeruli was increased at T1. However, progression of the glomerular lesions was minimal in most dogs. Worsening of tubulointerstitial scores was evident in the dogs with the most severe lesions at the first biopsy. Progression of the tubulointerstitial damage was minimal in the mildly affected dogs, and the interstitial inflammation was abated. In conclusion, renal lesions can progress over a 60-day period in canine leishmaniasis. A longer period between the renal biopsies would be necessary to demonstrate more severe changes. In addition a specific anti-Leishmania treatment could have a significant effect in the early stages of the disease.

Can estragole in fennel seed decoctions really be considered a danger for human health? A fennel safety update.

Fennel (Foeniculum vulgare Mill.) mature fruit (commonly known as seeds) and essential oil of fennel are widely used as flavoring agents in food products such as liqueurs, bread, cheese, and an ingredient of cosmetics and pharmaceutical products. Moreover fennel infusions are the classical decoction for nursing babies to prevent flatulence and colic spasm. Traditionally in Europe and Mediterranean areas fennel is used as antispasmodic, diuretic, anti-inflammatory, analgesic, secretomotor, secretolytic, galactagogue, eye lotion, and antioxidant remedy and integrator. Topically, fennel powder is used as a poultice for snake bites. In Asian cultures fennel was ingested to speed the elimination of poisons. As one of the ancient Saxon people's nine sacred herbs, fennel was credited with the power to cure. Fennel was also valued as a magic herb: in the Middle Ages it was draped over doorways on Midsummer's Eve to protect the household from evil spirits. Recently because of estragole carcinogenicity, fennel has been charged to be dangerous for humans especially if used as decoction for babies. But this allegation do not consider the remedy is prepared as a matrix of substances, and recent researches confirm that pure estragole is inactivated by many substance contained in the decoction.

Alopecia areata during treatment of psoriasis with adalimumab and leflunomide: a case and review of the literature.

The pathogenesis of alopecia areata (AA) is not clear, even though it is believed to be an autoimmune mechanism which involves T lymphocytes and cytokines such as tumor necrosis factor α. We report the case of a 43-year-old man with psoriasis and psoriatic arthritis who developed AA during his treatment with adalimumab and leflunomide. We perform a review of the literature associating AA with biological therapy and leflunomide. We cannot exclude that the use of these therapies and the development of AA could be coincidental. However, we consider that case reports like ours are essential for clinicians as early alerts if similar observations occur.

[Vaccinal prophylaxis against tetanus and hepatitis B: difficulties in application of law and actual status of workers' protection in Lombardy among workers of building sector]. / La profilassi vaccinale antitetanica ed antiepatite B: problematiche applicative della norma e state attuale della copertura tra i lavoratori del Comparto Edile in Lombardia.

Vaccinal prophylaxis is a preventive action which is compulsory, if available and useful for health protection of workers exposed to biological work risk. Definition andrealization of compulsory vaccinal campaigns is assigned by law to Occupational Health Doctor. We report a research carried out in 135 firms of building sector on 2158 workers exposed to biological work risk and concerning their vaccinal status against Tetanus and Hepatitis B. We found that only in a part of firms a plan of vaccination has been activated among workers exposed to biological work risk and, if activated, these plans frequently were partial and incomplete. Vaccinal protections among workers therefore resulted insufficient especially among foreigners workers and among workers active in first aid and emergency work teams. We think that a more active role of Occupational Health Doctors in promotion and realization of vaccinal campaigns is necessary for medico-legal and scientific reasons.

[Study of genetic polymorphisms in the tumor necrosis factor α promoter region in Spanish patients with psoriasis]. / Estudio de los polimorfismos genéticos de la región promotora del TNF-α en pacientes españoles afectos de psoriasis.

BACKGROUND: Several studies have reported an association between tumor necrosis factor α (TNF-α) polymorphisms and inflammatory diseases such as psoriasis vulgaris and psoriatic arthritis, although the results vary according to the population studied. No studies have been performed in the Spanish population. OBJECTIVE: To analyze the polymorphisms of the promoter region of the TNF-α gene in patients with moderate to severe psorasis and to identify potential differences in genotype compared to a group of healthy volunteers. MATERIAL AND METHODS: Eighty-nine patients with moderate to severe psoriasis and 76 healthy controls with no personal or family history of psoriasis were selected. Polymorphisms of the TNF-α promoter region of both groups were genotyped. RESULTS: We observed a higher prevalence of the genotype with both wild-type alleles at positions -238 (GG genotype, 86.5% vs 70.4%, respectively) and -1031 (TT genotype, 80.2% vs 45.8%, respectively) in patients compared to the healthy control group. The differences at positions -308 and -857 were not significant. CONCLUSION: There are differences in polymorphisms at positions -238 and -1031 in patients with moderate to severe psoriasis compared to healthy volunteers. This observation provides further support for the importance of the part that TNF-α plays in the pathophysiology of this disease.

3-T MRI with phased-array surface coil in the local staging of rectal cancer.

PURPOSE: This study sought to evaluate the diagnostic accuracy of surface-coil 3T magnetic resonance (MR) imaging in the preoperative study of patients with rectal cancer. MATERIALS AND METHODS: Thirty patients with histologically proven rectal cancer underwent surface-coil 3T MR imaging with sagittal, paracoronal and para-axial T2-weighted turbo spin echo (TSE) sequences. Slice thickness was 3 mm without gap, field of view 24 cm, matrix 400 × 512. Images were assessed for infiltration of the rectal wall, perirectal fat and pelvic structures. Tumours were staged according to the TNM system, and the MR imaging results were correlated with histopathology. RESULTS: In the patients who underwent MR imaging before and after radiotherapy (group 1), the diagnostic accuracy of 3T MR imaging was 88% for T2, 94% for T3 and 88% for T4 cancers. In those who underwent surgical treatment without preoperative radiotherapy (group 2), the diagnostic accuracy was 90% for T2, 87% for T3 and 87% for T4 cancers. CONCLUSIONS: The high signal-to-noise ratio coupled with a large field of view enables surface-coil 3T MR imaging to achieve high levels of diagnostic accuracy in the local staging of rectal cancer, and in particular in assessing infiltration of mesorectum and mesorectal fascia.

[Foreigner workers in Lombardy. Occupational, relational and cultural problems at work places]. / I lavoratori stranieri in Lombardia. Problematiche occupazionali, relazionali e culturali ai posti di lavoro.

Our research included 1359 foreigner citizens actually working in Lombardy. To better evaluate the eventual presence of relational, cultural and work related problems in their daily work experience we used a specific questionnaire, directly filled in by Occupational Doctors during occupational medical surveillance enforced by law, composed by different items concerning occupational and relational single worker's life. We evidenced that foreigner workers' population changed significantly in these last years loosing the characteristics of an homogeneous group. A foreigner workers' complete socio cultural integration in our country and specifically in working environments seems far to be really achieved.

Loss of nephrin expression in glomeruli of kidney-transplanted patients under m-TOR inhibitor therapy.

The development of proteinuria has been observed in kidney-transplanted patients on m-TOR inhibitor (m-TORi) treatment. Recent studies suggest that m-TORi(s) may alter the behavior and integrity of glomerular podocytes. We analyzed renal biopsies from kidney-transplanted patients and evaluated the expression of nephrin, a critical component of the glomerular slit-diaphragm. In a group of patients on 'de novo' m-TORi-treatment, the expression of nephrin within glomeruli was significantly reduced in all cases compared to pretransplant donor biopsies. Biopsies from control transplant patients not treated with m-TORi(s) failed to present a loss of nephrin. In a group of patients subsequently converted to m-TORi-treatment, a protocol biopsy performed before introduction of m-TORi was also available. The expression of nephrin in the pre-m-TORi biopsies was similar to that observed in the pretransplant donor biopsies but was significantly reduced after introduction of m-TORi(s). Proteinuria increased after the m-TORi inititiation in this group. However, in some cases proteinuria remained normal despite reduction of nephrin. In vitro, sirolimus downregulated nephrin expression by human podocytes. Our results suggest that m-TORi(s) may affect nephrin expression in kidney-transplanted patients, consistently with the observation in vitro on cultured podocytes.

Potential drug-drug interactions and radiodiagnostic procedures: an in-hospital survey.

OBJECTIVES: To evaluate the type, frequency, severity and predictors of potential Drug-Drug Interactions (DDIs) in a cohort of patients undergoing radiodiagnostic procedures. SETTING: Eight Radiology wards located in Tuscany (Italy). METHODS: All participants exposed to at least two medications were included in the analysis. DDIs were grouped according to their severity as 'minor', 'moderate' or 'major'. A logistic model was used to estimate Odds Ratios and 95% Confidence Intervals for all predictors of potential DDI. MAIN OUTCOME MEASURES: Type and predictors of potential DDI in a cohort of patients undergoing radiodiagnostic procedures. RESULTS: One-thousand-and-two subjects (57.6% females; mean age: 67.3 +/- 12.2) entered the analysis, and 46.1% of them incurred in a potential DDI (78.9% 'moderate' in severity). The combination of allopurinol and ACE-inhibitors was the most frequent (21/153) among major potential DDIs, while steroids were involved in all cases of potential DDI due to premedication. Co-morbidity, number of co-medications, advanced age and premedication use increased the risk of potential DDI; a protective role was found for positive history of allergy. When the analysis was restricted to subjects with premedication (n = 93), only 12.9% of them reported a potential DDI directly attributable to premedication drugs. CONCLUSIONS: Among patients undergoing radiological examination, types and predictors of potential DDIs appeared in agreement with other kind of in-hospital populations. Premedication revealed to be a proxy predictor for potential DDIs. Considering the poor capability of the prescriber in recognizing interactions, their systematic evaluation (using an informatics tool) in patients undergoing radiological examination might be helpful in preventing the occurrence of clinically relevant DDIs.