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but the choice of intervention for a particular patient is determined by tumor factors such as site&#44; size&#44; whether primary or recurrent tumor and histological or clinical subtypes&#46; Additionally&#44; patient factors &#40;comorbidities&#44; cosmetic results&#44; preferences&#41; and setting factors &#40;available material and human resources&#44; and cost&#41; must be considered in the decision-making process&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">According to current clinical guidelines&#44; stratification based on the risk of recurrence is the first step in the clinical management of BCC&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> Most guidelines follow the stratification rules from the National Comprehensive Cancer Network &#40;NCCN&#41; that take into account a combination of different parameters that split BCC into high-risk and low-risk tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Interventions are usually classified as surgical and non-surgical therapy&#46; Surgical therapy is recommended as first-line treatment for both high-risk and low-risk BCC subtypes&#44; though non-surgical interventions are usually reserved for low-risk BCC&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">When surgery is not an option&#44; there are a plethora of non-surgical interventions for low-risk BCC&#44; all with acceptable recurrence rates and excellent cosmetic outcomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> It is different for high-risk tumors&#44; in which Radiotherapy &#40;RT&#41; is the first&#44; and frequently the only&#44; feasible option&#46; Evaluations of other interventions for facial high-risk BCC&#44; in which surgery is not possible &#40;or desirable&#41;&#44; are currently needed&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Interferons have been evaluated as a local treatment for BCC&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;12</span></a> Even when early studies have shown acceptable efficacy and safety outcomes&#44; mainstream current guidelines do not recommend interferons for any type of BCC&#46; As we have not found a convincing explanation or an insightful discussion on the reasons for this omission&#44; we suggest there is a place for the evaluation of the effectiveness and safety of perilesional interferon&#44; especially in facial high-risk BCC in which surgery is not an option&#46; An important systematic review aimed at evaluating the evidence of different therapeutic interventions for BCC gives this brief argument against the pertinence of using interferons for BCC&#58; the treatment usually needs to be delivered over multiple sessions and is expensive which limits its widespread use&#46; Systemic side effects are common&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">HeberFERON&#44; a combination of alfa-2b and gamma interferons&#44; is a biopharmaceutical developed by the Center for Genetic Engineering and Biotechnology&#44; Havana&#44; Cuba&#44; and approved by the Cuban regulatory authorities for the treatment of BCC&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> A real-world retrospective study of BCC patients treated with HeberFERON described the treatment response in a Cuban cohort&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> That study has important limitations&#58; authors only evaluated cure rates after 16 weeks of treatment without a long-term follow-up period&#46; Recurrence at five years has been considered as the primary endpoint when evaluating the efficacy&#47;effectiveness of any interventions for local BCC&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The aim of this study was to evaluate the long-term clinical response to interferon therapy in patients with high-risk facial BCC&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Study design and setting</span><p id="par0040" class="elsevierStylePara elsevierViewall">This was a prospective&#44; observational&#44; multicenter&#44; cohort study&#44; with a follow-up period of five years&#46; Six health centers of primary care from different municipalities of the province of Sancti Spiritus&#44; Cuba&#44; participated in the study&#46; Each health center was equipped with a surgical facility and a trained dermatologist with more than 10 years of experience on treating patients with BCC&#46; The study was carried out in the environment of real-world clinical practice&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Participants</span><p id="par0045" class="elsevierStylePara elsevierViewall">Patients attained dermatology services from primary health centers after a referral from the superficial tumor multidisciplinary team for the evaluation and management of clinically diagnosed BCC&#46; Only patients that meet the following criteria were selected for further evaluation&#58; adults &#40;more than 18 years old&#41; of either sex&#44; with single or multiple facial biopsy confirmed BCCs of any size&#44; subtype&#44; recurrent or not&#44; with or without tumor prior treatments&#46; Other criteria include that surgical treatment was not possible or desirable&#44; and no contraindications for receiving HeberFERON &#40;according to instructions from the drug manufacturer or dermatologist consideration&#41;&#46; Signing of a written informed consent for participation was also needed for inclusion in the study&#46; After initial screening&#44; only those patients with tumors classified as high-risk&#44; following the National Comprehensive Cancer Network &#40;NCCN&#41; criteria&#44; were included in the study&#46; The recruitment period extended from June 17&#44; 2015 to February 28&#44; 2018 and the follow-up period ended on March 20&#44; 2023&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Interventions</span><p id="par0050" class="elsevierStylePara elsevierViewall">Interventions were carried out by experienced dermatologists&#44; previously trained&#44; and certified for the administration of HeberFERON&#46; In the initial encounter&#44; history and physical examination were carried out&#46; Information regarding the location and size of the tumor&#44; clinical and histological subtype&#44; dermatoscopic evaluation&#44; and whether it was a primary or recurrent tumor&#44; among others&#44; were also obtained&#46; Blood samples were taken for routine laboratory tests&#46; A 3&#8239;mm punch biopsy for histological study was performed&#46; All the information was recorded prospectively in the patient&#39;s clinical record&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">HeberFERON&#44; a synergistic combination of interferons-&#945; and -&#947; &#40;HeberPAG&#44; Heber Biotec SA&#44; Havana&#44; Cuba&#41;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a> was employed for the treatment of patients&#46; A trained dermatologist administered the drug&#44; the dose was 10&#46;5&#8239;&#215;&#8239;10<span class="elsevierStyleSup">6</span> IU and the route was intradermal&#47;perilesional&#44; three times per week&#44; for three consecutive weeks&#46; In each encounter&#44; patients were interviewed and examined&#46; Patients were observed 90&#8239;minutes after the administration of the drug and every acute adverse event was recorded&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The follow-up period started once the patient was included and the first doses were administered&#46; One month after the treatment schedule was completed&#44; patients were evaluated with the inspection &#40;measurements&#41; of the lesions&#44; interviewed about adverse events&#44; and the same set of laboratory analyses was indicated for compassion&#46; At 16 weeks after the initiation of treatment&#44; another evaluation was performed &#40;biopsy included&#41; in order to determine the clinical responses and adverse events&#46; Each follow-up visit includes a dermatological&#44; dermatoscopic and ganglionic exam&#46; Each patient was followed up for a minimum of 60 months&#59; every three-month during the first year&#44; twice a year during the second year&#44; and once a year thereafter&#46; All patients received indications on whether they noticed any new lesion in the skin&#44; of any type and location&#44; in the time interval between each planned appointment&#44; then&#44; they must go to the doctor for evaluation&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Outcomes</span><p id="par0065" class="elsevierStylePara elsevierViewall">Three outcome variables characterized the effectiveness of therapy&#58; clinical response&#44; recurrence&#44; and development of new primary BCC&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Clinical response was measured by a trained dermatologist 16 weeks after the first doses&#46; Four categories of clinical responses were considered&#58; complete response &#40;complete elimination of tumor from the clinical&#44; dermatoscopic and histopathological point of view&#41;&#59; partial response &#40;reduction of more than 30&#37; of tumor size&#41;&#59; stable disease &#40;reduction of tumor size not enough to be considered partial response or progressive disease&#41;&#59; and progressive disease &#40;more than 20&#37; increase of tumor size&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Recurrence was considered when&#44; after a period of complete response&#44; a tumor of the same histological subtype reemerged in the same location&#46; The development of a new BCC was contemplated when a new tumor emerged at a different site&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Adverse events were recorded and coded according to WHO-ART&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0085" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using the software package SPSS &#40;version 22&#41;&#46; Quantitative variables were described with the arithmetic mean and its standard deviation&#46; Absolute and relative frequency &#40;&#37;&#41; were used for qualitative variables&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The influence of demographic and tumor variables on clinical response were tested using univariate analyses by the Chi-Squared as an association measure with the Odds Ratio &#40;OR&#41; and 95&#37; Confidence Interval &#40;95&#37; CI&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Recurrence and the development of a new BCC were analyzed with a Kaplan-Meier survival analysis to estimate the mean time to event with its 95&#37; CI&#46; For both endpoints &#40;recurrence and development of a new BCC&#41;&#44; global survival &#40;with its 95&#37; CI&#41; was estimated for 5-year follow-up&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Ethical considerations</span><p id="par0100" class="elsevierStylePara elsevierViewall">The Institutional Ethical Board approved the protocol for this study&#46; All participants gave their written informed consent&#46; The procedures and data management were in accordance with Good Clinical Practice guidelines and the ethical principles stated in the Declaration of Helsinki&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0105" class="elsevierStylePara elsevierViewall">Five hundred and twenty-eight patients with a clinical diagnosed BCC were evaluated during the recruitment period and only 195 fulfilled the inclusion criteria &#40;facial&#44; high-risk&#44; histologically confirmed BCC&#44; not susceptible to surgery&#41;&#46; Baseline sociodemographic and tumor characteristics of included patients are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Regarding clinical response&#44; 143 &#40;73&#46;3&#37;&#41; patients showed a complete response &#40;95&#37; CI 67&#46;2&#8210;80&#46;1&#41;&#59; 49 &#40;25&#46;1&#37;&#41; patients presented a partial response and 2 &#40;1&#37;&#41; presented stable disease&#46; One patient abandoned therapy during the initial sections&#46; The clinical complete responses were corroborated by biopsy in 107 patients&#59; the rest of the patients with clinical complete responses did not accept a second biopsy procedure&#46; Patients without complete response&#44; after previous discussion and reevaluation with the dermatologist&#44; qualified for surgical excision&#46; Then&#44; all 194 patients &#40;143 treated with HeberFERON and 51 treated with HeberFERON plus surgery&#41; were considered cured and then followed up for five-years&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The univariate analyses by the Chi-Squared test showed that only two variables were associated with a specific clinical response&#58; age more than 72 years &#40;OR&#8239;&#61;&#8239;3&#46;10&#44; 95&#37; CI 1&#46;57&#8210;6&#46;11&#41; and lesion size more than 20&#8239;mm &#40;OR&#8239;&#61;&#8239;2&#46;25&#44; 95&#37; CI 1&#46;14&#8210;4&#46;41&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Regarding histological subtypes&#44; 130 patients out of 182 with non-aggressive tumors showed a complete clinical response&#46; On the other hand&#44; 10 out of 13 patients with aggressive histological subtypes presented a complete response&#59; however&#44; 40&#37; of aggressive tumors developed a recurrence after 5 years of follow-up&#46; The patients with morphea form subtypes showed a complete response without recurrence but developed a second primary BCC in another site&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Kaplan-Meier survival analysis showed the time to event for recurrence in 194 patients &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Patients developed a recurrence with a mean of 55 months &#40;95&#37; CI 53&#46;8&#8210;57&#46;4&#41;&#46; The estimated rate of recurrence was 12&#46;3&#37; &#40;95&#37; CI 7&#46;4&#8210;17&#46;1&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows survival analysis for the development of a new primary BCC&#46; Patients developed a new BCC within a mean of 52&#46;7 months &#40;95&#37; CI 50&#46;4&#8210;54&#46;9&#41;&#46; The estimated rate for the development of a new BCC at five years was 20&#46;0&#37; &#40;95&#37; CI 14&#46;2&#8210;25&#46;9&#41;&#46; Fifteen &#40;7&#44;7&#37;&#41; abandoned the study during the five-year follow-up period&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRefs" href="#fig0015">Figs&#46; 3 and 4</a> show pictures as examples of the clinical responses and evolutions of patients&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">The type and frequency of adverse events are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; All patients experienced any adverse event&#46; Fever&#44; pain in the injection site&#44; headache&#44; asthenia&#44; arthralgia&#44; and chills were the most frequent adverse events&#46; Most of the events were mild &#40;25&#37;&#41; or moderate &#40;75&#37;&#41;&#44; were transient&#44; and manifested only during the treatment period&#46; It was not necessary the definitive interruption of treatment &#40;except in one patient who abandoned therapy without explanation&#41; and&#44; only on 24 occasions&#44; therapy was temporarily interrupted due to adverse events&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0145" class="elsevierStylePara elsevierViewall">Local administration of interferons has been used sporadically for the treatment of BCC<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;12</span></a> but most recent clinical guidelines do not recommend this type of therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> This study evaluated the effect of perilesional administration of HeberFERON &#40;a combination of alpha-2b and gamma interferons&#41; in 195 patients with high-risk facial BCC not suitable for surgical treatment&#46; The study was carried out in the context of real-world clinical practice in several medical centers in the province of Sancti Spiritus&#44; Cuba&#46; The effectiveness was evaluated by means of three principal endpoints&#58; clinical response at 16 weeks&#44; recurrence&#44; and development of a new primary BCC after five years of follow-up&#46; To our knowledge&#44; this is the first study that evaluates the long-term effect of local interferon in a large cohort of patients with facial high-risk BCC&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Most patients 73&#46;3&#37; &#40;95&#37; CI 67&#46;2&#37;&#8210;80&#46;1&#37;&#41; showed a complete response 16 weeks after the initiation of therapy&#46; Only two variables&#44; age more than 72 years and lesion size more than 20&#8239;mm were associated with a poor clinical response&#46; Aggressive histological subtypes have been associated with poor clinical response&#44; that correlation was not found in the present study perhaps due to the fact there were only 13 aggressive BCCs in the cohort that preclude a statistically significant result&#46; The patient with a morphea form subtype showed a complete response without recurrence but developed a second primary BCC in another site&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Patients with partial response became then suitable for surgical excision and were considered cured once their tumors were removed&#46; Both groups &#40;those treated exclusively with HeberFERON and those treated with HeberFERON plus surgery&#41; were then followed up for five years&#46; Survival analysis estimated that the recurrence rate after five years of follow-up was 12&#46;3&#37; &#40;95&#37; CI 7&#46;4&#8210;17&#46;1&#41;&#46; Five years rate of recurrence has been considered as an important endpoint when evaluating the efficacy&#47;effectiveness of any therapy for BCC&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> As we do not have a comparison group in this study&#44; we are going to use this endpoint for comparison with competing therapies such as RT&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">RT is a well-established treatment modality for BCC&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> It can be used at any stage of the disease&#44; as an exclusive or adjuvant therapy and with curative or palliative purposes&#46; When surgery is not an option&#44; especially for facial BCC&#44; RT is the treatment of choice&#46; There are different RT modalities but the most extensively studied are External-Beam RT &#40;EBRT&#41; and high-dose-rate Brachytherapy &#40;BT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Lee CT et al&#46; have published an international meta-analysis of 58 studies with 2100 patients&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> We considered this article as the most recent and complete source of information on the effect of RT in BCC&#46; Authors measured cosmesis as the primary endpoint and recurrence at one and five years as secondary endpoints&#46; Since we do not measure cosmesis in the present study&#44; five-year recurrent rates will be the figure for comparison&#46; The meta-analysis estimated a five-year recurrence rate of 6&#46;7&#37; &#40;95&#37; CI 5&#46;5&#8210;8&#46;5&#41; for LRBT and 2&#46;4&#37; &#40;95&#37; CI 0&#46;2&#8210;5&#46;1&#41; for BT&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> These figures are barely better than those obtained in this study&#44; and there is a slight overlap between theirs and ours 95&#37; CI&#46; This comparison must be interpreted with caution as this cohort is composed exclusively of patients with facial high-risk BCC&#44; while studies included in the meta-analysis are heterogeneous and comprise both high-risk and low-risk tumors&#46; Another aspect that must be taken into account is that&#44; as RT has been used for decades&#44; there are recent technical and protocol improvements that offer much better results that could not be revealed in the meta-analysis&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Even when there is persuasive evidence on the efficacy&#47;effectiveness and safety that support the convenience of including interferon in the therapeutic arsenal for BCC&#44;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;12</span></a> major concerns against this recommendation are that the treatment must be delivered over multiple sessions and that it is expensive&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Both two drawbacks could be adjudicated to RT as well&#46; Cost of Hospital-based hypofractionated RT for a single BCC ranges from &#36;2000 to &#36;8000 US dollars&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> EBRT may need 15&#8210;30 patients visits to treat an individual tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Moreover&#44; there is an important concern on the striking 20-fold increase from 2011 to 2013 in the use of Current Procedural Terminology &#40;CPT&#41; codes for electronic brachytherapy in Medicare patients&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Authors speculate that those figures seem to be chosen by economic incentives rather than true clinical needs&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Furthermore&#44; experts consider that the present high-tech RT modalities are often not well known or misunderstood by members of the highly specialized multidisciplinary team and&#44; in the absence of a radiation-oncologist at the multidisciplinary tumor board&#44; RT is likely underused&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> This fact&#44; limit the possibility of using RT in many settings or increase their cost&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">About 40&#37; of patients that have been cured of previous BCC develop a new tumor in the next five years&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> In a previous report of patients with nonmelanoma skin cancer treated with HeberFERON&#44; an apparent reduction in the development of new BCC have been noted&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Authors speculate that the presence of interferon in nearby tissue could be inhibitory for the development of new tumors&#46; The survival analysis for the occurrence of new BCC in our cohort showed that the estimated probability of occurrence of new BCC was 20&#37; &#40;95&#37; CI 14&#46;2&#8210;25&#46;1&#41;&#46; That figure is lower than expected but the possibility of a preventive role in the development of a new BCC through the use of HeberFERON should be determined in future work&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The safety profile for HeberFERON in the cohort has been similar to those from previous studies with topical interferons for BCC and the authors considered it as acceptable&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;12</span></a> All patients developed at least one adverse event&#59; fever&#44; local pain&#44; and irritation in the injection site were the most common&#46; Even when they were various and common&#44; they were transient&#44; not severe and it was not necessary to interrupt the therapeutic schedule due to adverse events&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">This study has several limitations&#46; The observational design&#44; without a parallel group for comparison&#44; is not ideal for the evaluation of the efficacy&#47;effectiveness of any therapeutic intervention&#46; The heterogeneity of the disease regarding different factors such as tumor site&#44; location&#44; and histological and clinical subtypes&#44; which may affect the outcomes&#44; entail inconveniences for a suitable Randomized Controlled Trial &#40;RCT&#41;&#44; in fact&#44; most studies in the literature of BCC utilize observational designs such as ours&#46; As the endpoints were measured by the same persons who administered the drug&#44; there could be some bias in favor of a better response&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Strengths of the study include the acceptable number of patients with relatively homogeneous characteristics &#40;high-risk facial BCC&#41;&#46; Due to the intrinsic heterogeneity of this disease&#44; most of the published cohorts are composed of a mixture of patients with low and high risk of recurrences&#44; even when guidelines recommended different treatment modalities for each group&#46; The low rate &#40;7&#46;7&#37;&#41; of abandons during follow-up&#44; the fact that the authors have selected a follow up period and clinical endpoints that have been considered as important for including studies in systematic reviews and meta-analyses&#44; are also contemplated as strengths&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors conclude that perilesional administration of HeberFERON &#40;a combination of alpha-2b and gamma interferons&#41; in patients with facial high-risk BCC&#44; offers a satisfactory cure rate after a five-year follow-up with an acceptable safety profile&#46; This treatment modality deserves further consideration for being included in the therapeutic armamentarium for facial BCC&#46; For this purpose&#44; a comparison with RT in a parallel RCT design that measures a five-year local recurrence rate&#44; development of a new BCC&#44; cosmesis&#44; patient acceptance&#44; and cost&#44; will be desirable&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Financial support</span><p id="par0200" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Authors&#39; contributions</span><p id="par0205" class="elsevierStylePara elsevierViewall">Vladimir S&#225;nchez&#58; Approval of the final version of the manuscript&#59; critical literature review&#59; data collection&#44; analysis&#44; and interpretation&#59; effective participation in research orientation&#59; intellectual participation in propaedeutic and&#47;or therapeutic management of studied cases&#59; critical manuscript review&#59; preparation and writing of the manuscript&#59; statistical analysis&#59; study conception and planning&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Emilio Carpio&#58; Approval of the final version of the manuscript&#59; critical literature review&#59; data analysis&#44; and interpretation&#59; effective participation in research orientation&#59; critical manuscript review&#59; preparation and writing of the manuscript&#59; statistical analysis&#59; study conception and planning&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Vicente Eloy Fardales&#58; Approval of the final version of the manuscript&#59; critical literature review&#59; analysis and interpretation od data&#59; effective participation in research orientation&#59; critical manuscript review&#59; preparation and writing of the manuscript&#59; statistical analysis&#59; study conception and planning&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Belkys Mart&#237;nez&#58; Approval of the final version of the manuscript&#59; data collection&#59; intellectual participation in propaedeutic and&#47;or therapeutic management of studied cases&#59; critical manuscript review&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Ana Iris Arias&#58; Approval of the final version of the manuscript&#59; data collection&#59; intellectual participation in propaedeutic and&#47;or therapeutic management of studied cases&#59; critical manuscript review&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Elizabeth Brito&#58; Approval of the final version of the manuscript&#59; data collection&#59; intellectual participation in propaedeutic and&#47;or therapeutic management of studied cases&#59; critical manuscript review&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Niurka Bermudez&#58; Approval of the final version of the manuscript&#59; data collection&#59; intellectual participation in propaedeutic and&#47;or therapeutic management of studied cases&#59; critical manuscript review&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Yoel Rodr&#237;guez&#58; Approval of the final version of the manuscript&#59; data collection&#59; intellectual participation in propaedeutic and&#47;or therapeutic management of studied cases&#59; critical manuscript review&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of interest</span><p id="par0245" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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            0 => array:2 [
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              "titulo" => "Study design and setting"
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              "titulo" => "Outcomes"
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              "identificador" => "sec0035"
              "titulo" => "Statistical analysis"
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              "identificador" => "sec0040"
              "titulo" => "Ethical considerations"
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          "titulo" => "Results"
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          "titulo" => "Financial support"
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          "titulo" => "Conflicts of interest"
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          "titulo" => "References"
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    "fechaRecibido" => "2023-07-08"
    "fechaAceptado" => "2023-08-29"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1814424"
          "palabras" => array:4 [
            0 => "Carcinoma&#44; basal cell"
            1 => "Dermatology"
            2 => "Interferons"
            3 => "Therapeutics"
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    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Surgery is the treatment of choice for patients with basal cell carcinoma &#40;BCC&#41;&#46; When surgery is not a choice&#44; only radiotherapy is recommended for patients with high-risk facial BCC&#46; Interferon could be an acceptable therapeutic option for these patients&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">To evaluate the long-term clinical response to interferon therapy in patients with high-risk facial BCC&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Patients with high-risk facial BCC were treated with perilesional injections of alpha-2b&#43; gamma interferons&#46; Those with incomplete clinical response were reevaluated&#44; their residual tumors excised&#44; and declared cured&#46; Patients treated with interferon and those treated with interferon plus surgery were followed for five years&#46; Time to recurrence and the emergence of a new facial BCC were estimated by Kaplan-Meier survival analysis&#46; Adverse events were documented&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">This study included 195 participants&#59; 143 &#40;73&#46;3&#37;&#41; showed a complete response &#40;95&#37; CI 67&#46;2&#8210;80&#46;1&#41;&#46; Patients developed recurrence after a mean of 55 months &#40;95&#37; CI 53&#46;8&#8210;57&#46;4&#41;&#46; The estimated rate of recurrence was 12&#46;3&#37; &#40;95&#37; CI 7&#46;4&#8210;17&#46;1&#41;&#46; Patients developed a new BCC after a mean of 52&#46;7 months &#40;95&#37; CI 50&#46;4&#8210;54&#46;9&#41;&#46; The estimated rate for development of a new BCC was 20&#46;0&#37; &#40;95&#37; CI 14&#46;4&#8210;25&#46;9&#41;&#46; Fifteen &#40;7&#46;7&#37;&#41; patients abandoned the study during follow-up&#46; Adverse events were frequent but moderate or mild&#59; fever and local pain were the most frequent&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Study limitations</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Observational cohort design without a control group for comparison&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Perilesional injections of alpha-2b&#43; gamma interferons in patients with facial high-risk BCC offer a satisfactory cure rate after five years of follow-up with an acceptable safety profile&#46;</p></span>"
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            "titulo" => "Conclusions"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Study conducted at the Juana Naranjo Leon&#44; Sancti Sp&#237;ritus&#44; Cuba&#46; Polyclinic Camilo Cienfuegos&#44; Yaguajay&#44; Sancti Sp&#237;ritus&#44; Cuba&#46; Polyclinic Manuel de Jes&#250;s Lara Cantero&#44; Trinidad&#44; Sancti Sp&#237;ritus&#44; Cuba&#46; Center Polyclinic Juana Naranjo Leon&#44; Sancti Sp&#237;ritus&#44; Cuba&#46; Polyclinic Antonio &#193;vila Valdivia&#44; Jatibonico&#44; Sancti Sp&#237;ritus&#44; Cuba&#46; Arcelio Su&#225;rez Bernal&#44; Jatibonico&#44; Sancti Sp&#237;ritus&#44; Cuba&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Survival analysis for the development of local recurrence&#46;</p>"
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#44;75&#8239;&#177;&#8239;12&#44;11 &#40;37-93&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sex&#44; Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">119 &#40;61&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Occupation exposed to sun&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">143 &#40;73&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Skin type&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98 &#40;50&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90 &#40;46&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;3&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Family background of skin cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 &#40;38&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lesion Size<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;43&#8239;&#177;&#8239;10&#44;91 &#40;0&#44;3-50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical Subtypes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nodular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#40;30&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Superficial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;4&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nodular pigmented&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;9&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nodular ulcerative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79 &#40;40&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Morpheaform&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;14&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Histological Subtypes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-aggressive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">182 &#40;93&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Solid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">154 &#40;79&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adenoid cystic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;4&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Superficial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;10&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aggressive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;6&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inf&#237;ltrative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;4&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Basosquamous&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Micronodular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Morpheaform&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Location&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">upper lip&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;1&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">nose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">93 &#40;47&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">periocular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;13&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">frontal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;6&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">cheeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;13&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">temporal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;3&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pinna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;11&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">retroauricular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;1&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">inferior maxillary&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Previous treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">82 &#40;42&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76 &#40;39&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5- FU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;2&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HeberFERON&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Baselines characteristics of patients with facial high-risk basal cell carcinoma n&#8239;&#61;&#8239;195&#46;</p>"
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            "identificador" => "at0030"
            "detalle" => "Table "
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients with the event&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">&#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">195&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pain in the injection site&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">195&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">185&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Asthenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">131&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Arthralgia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">129&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Edema in the site of injection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chills&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nausea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diarrhea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vomits&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Local sepsis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Most frequent adverse events in patients treated with HeberFERON&#46;</p>"
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      "titulo" => "References"
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        0 => array:2 [
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