Wide Excision in Hidradenitis Suppurativa. Does it Modify the Course of Disease? / Escisión amplia en hidradenitis supurativa. ¿Modifica el curso de la enfermedad?

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 (AU)

No existen estudios que se centren en la utilidad del tratamiento con cirugía amplia para el control global de la hidradenitis supurativa. En el presente estudio hemos evaluado el curso de la enfermedad de 17 pacientes con hidradenitis supurativa a los que se les realizó extirpación de trayectos fistulosos mediante cirugía amplia entre octubre de 2018 y enero de 2022 en el Hospital Universitario de La Princesa. Encontramos como resultado que el tratamiento mediante cirugía amplia produce un beneficio global en la actividad inflamatoria de la enfermedad y puede ser importante para el control de la hidradenitis supurativa (AU)

[Artículo traducido] Escisión amplia en hidradenitis supurativa. ¿Modifica el curso de la enfermedad / Wide Excision in Hidradenitis Suppurativa. Does it Modify the Course of Disease?

No existen estudios que se centren en la utilidad del tratamiento con cirugía amplia para el control global de la hidradenitis supurativa. En el presente estudio hemos evaluado el curso de la enfermedad de 17 pacientes con hidradenitis supurativa a los que se les realizó extirpación de trayectos fistulosos mediante cirugía amplia entre octubre de 2018 y enero de 2022 en el Hospital Universitario de La Princesa. Encontramos como resultado que el tratamiento mediante cirugía amplia produce un beneficio global en la actividad inflamatoria de la enfermedad y puede ser importante para el control de la hidradenitis supurativa (AU)

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 (AU)

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.

Contralateral axillary sentinel lymph node drainage in breast cancer: Controversies and management according to the literature. A case report. / Drenaje del ganglio centinela a axila contralateral en cáncer de mama: controversias y manejo según la literatura. A propósito de un caso.

Lymphoscintigraphy in breast cancer usually shows lymphatic drainage to the ipsilateral axilla. Drainage to extraaxillary or contralateral axillary regions is rare and there is still controversy about its management. Due to the significant clinical impact of an accurate staging, a literature research is made based on a case of a patient with recurrence of left breast cancer with contralateral axillary sentinel lymph node detection, without evidence of lymphatic drainage to other locations.

Tratamiento actual y nuevas terapias contra la infección crónica por el virus de la hepatitis B / Current treatment and new therapies against chronic hepatitis B virus infection

Resumen La infección crónica por el virus de la hepatitis B (VHB) es un grave problema de salud pública a nivel mundial. Sus consecuencias llegan a ser mortales y el tratamiento actual no ofrece curación sino control de la enfermedad. Las principales limitantes para una cura son la dificultad para destruir el ADN circular covalente cerrado (ADNccc) del virus en el núcleo celular y la presencia de material genético viral integrado en el ADN de la célula hospedera. No obstante, hay múltiples frentes de investigación enfocados en encontrar una cura definitiva al potenciar la respuesta inmune del hospedero o al actuar directamente contra el virus y su ciclo de replicación. En este artículo se exponen los principales avances que se han realizado en este campo.

Abstract Chronic hepatitis B virus infections are a serious public health problem worldwide. Its consequences can be deadly, and current treatment offers only control of the disease rather than a cure. The main limiting factors for a cure are the difficulty of destroying the cDNA of the virus in the cell nucleus and the presence of viral genetic material integrated into the DNA of the host cell. Multiple fronts of research focus on finding a definitive cure by enhancing the immune response of the host or by acting directly against the virus and its replication cycle. This article presents the main advances that have been made in this field.

[Imaging diagnosis in Focal Therapy for prostate cancer: Multiparametric Magnetic Resonance Imaging]. / Diagnóstico por imágen en Terapia Focal para el cáncer de próstata: Resonancia Magnética multiparamétrica.

The use of prostatic multiparametric MRI (mpMRI) has increased significantly over the last years, and has emerged as a crucial test for diagnosis, staging and treatment of prostate cancer (PCa). The use of the various available sequences (T2W, T1W, diffusion, perfusion and spectroscopy), as well as the different parameters they associate, not only enables to determine the group of patients subsidiary of focal ablative therapy, but also to perform a proper determination of the áreas to treat, as well as to monitor the development of therapy and to evaluate both oncological results and possible therapeutic failures. Despite the excellent results showed in the different studies, it is necessary to reach a consensus about its use on the different features associated with focal therapy, since it is a technique that requires not only large experience in its operation but also standardization. All this make it a complex technique and not free of difficulties in its interpretation.

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.

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.

Tyr1068-phosphorylated epidermal growth factor receptor (EGFR) predicts cancer stem cell targeting by erlotinib in preclinical models of wild-type EGFR lung cancer.

Tyrosine kinase inhibitors (TKIs) have shown strong activity against non-small-cell lung cancer (NSCLC) patients harboring activating epidermal growth factor receptor (EGFR) mutations. However, a fraction of EGFR wild-type (WT) patients may have an improvement in terms of response rate and progression-free survival when treated with erlotinib, suggesting that factors other than EGFR mutation may lead to TKI sensitivity. However, at present, no sufficiently robust clinical or biological parameters have been defined to identify WT-EGFR patients with greater chances of response. Therapeutics validation has necessarily to focus on lung cancer stem cells (LCSCs) as they are more difficult to eradicate and represent the tumor-maintaining cell population. Here, we investigated erlotinib response of lung CSCs with WT-EGFR and identified EGFR phosphorylation at tyrosine1068 (EGFRtyr1068) as a powerful biomarker associated with erlotinib sensitivity both in vitro and in preclinical CSC-generated xenografts. In contrast to the preferential cytotoxicity of chemotherapy against the more differentiated cells, in EGFRtyr1068 cells, erlotinib was even more active against the LCSCs compared with their differentiated counterpart, acquiring potential value as CSC-directed therapeutics in the context of WT-EGFR lung cancer. Although tumor growth was inhibited to a similar extent during erlotinib or chemotherapy administration to responsive tumors, erlotinib proved superior to chemotherapy in terms of higher tolerability and reduced tumor aggressiveness after treatment suspension, substantiating the possibility of preferential LCSC targeting, both in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) tumors. We conclude that EGFRtyr1068 may represent a potential candidate biomarker predicting erlotinib response at CSC-level in EGFR-WT lung cancer patients. Finally, besides its invariable association with erlotinib sensitivity in EGFR-WT lung CSCs, EGFRtyr1068 was associated with EGFR-sensitizing mutations in cell lines and patient tumors, with relevant diagnostic, clinical and therapeutic implications.

A mechanistic investigation of the ruthenium porphyrin catalysed aziridination of olefins by aryl azides.

A mechanism for the aziridination of olefins by aryl azides (ArN3), promoted by ruthenium(ii) porphyrin complexes, is proposed on the basis of kinetic and theoretical studies. All the recorded data support the involvement of a mono-imido ruthenium complex as the active intermediate in the transfer of the nitrene moiety "ArN" to the olefin. The selectivity of the aziridination vs. the uncatalysed triazoline formation can be enhanced by fine-tuning the electronic features of the porphyrin ligand and the olefin/azide catalytic ratio. The DFT study highlights the importance of an accessible triplet ground state of the intermediate ruthenium mono-imido complex to allow the evolution of the aziridination process.

Assessment of platelet function analyzer (PFA-100) in kidney transplant patients before renal allograft biopsy: a retrospective single-center analysis.

BACKGROUND: Kidney biopsy (KB) represents the criterion standard to obtain information on diagnosis and prognosis of renal allograft dysfunctions. However, it can be associated with bleeding complications (BCs). Bleeding time test (BTT), the best predictive indicator of post-biopsy BCs, is not a very reproducible test and is invasive. Therefore, the aim of this study was to evaluate whether the platelet function analyzer (PFA-100), a very reliable test to investigate primary hemostasis, could be useful in predicting the risk of bleeding complications in transplant patients undergoing KB. METHODS: We carried out a retrospective analysis of PFA-100 collagen-epinephrine (C-EPI) and collagen-adenosine diphosphate (C-ADP) closure times in 119 patients undergoing KB in our center. Data regarding BTT, age, sex, blood pressure, number of renal allograft punctures for each biopsy procedure, thromboplastin time, prothrombin time, complete blood count, and prophylactic therapy with desmopressin were also collected. Major (need for blood transfusion) or minor (no need for any intervention) BCs (hematoma and hematuria) were recorded. RESULTS: Indications for KB were: delayed graft function (n=23), allograft dysfunction (n=40), proteinuria (n=27), allograft dysfunction plus proteinuria (n=19), and protocol biopsy (n=10). Nine of the 119 patients (7.5%) developed minor BCs (6 macrohematuria, 3 hematoma), major BCs did not develop. No significant differences were found in any of the clinical and laboratory data, including BTT and PFA-100 (C-EPI and C-ADP) between patients who developed BCs compared with those who did not. In addition, there was no correlation between PFA-100 test (C-EPI and C-ADP) values and BTT data [R2=0.002; P=.6]. CONCLUSIONS: The PFA-100 test was not useful in predicting the risk of BCs in kidney transplant patients undergoing renal allograft biopsy.

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.

Combined HPLC-DAD-MS, HPLC-MS(n) and NMR spectroscopy for quality control of plant extracts: the case of a commercial blend sold as dietary supplement.

The efficiency of 1D and 2D NMR spectroscopy along with HPLC-DAD-MS analyses in characterising the content of a dietary supplement is demonstrated. Experiments directly performed on a lyophilised sample of a commercial product gave details on the quality control of the product. The lack of the marker constituents of some of the declared plant species (Crataegus oxyacantha, Olea europea, Capsella bursa-pastoris and Fumaria officinalis) and the presence of banned adulterants, responsible for the strong antihypertensive effect of the supplement were established. The analyses proved the presence of indole alkaloids belonging to the group of Rauwolfia sp., such as ajmaline, reserpine and yohimbine. Quantitative HPLC analysis showed that the content of reserpine in the product was in the therapeutic range and therefore responsible for the collapses of the patients.