Active surveillance for clinical complete responders after chemoradiotherapy for oesophageal squamous cell carcinoma.

BACKGROUND: Guidelines on the treatment of oesophageal squamous cell carcinoma (SCC) recommend neoadjuvant chemoradiotherapy plus surgery or definitive chemoradiotherapy. The aim of this study was to evaluate the outcome of patients with a cCR after chemoradiotherapy who underwent active surveillance. METHODS: Patients with oesophageal SCC who were treated with chemoradiotherapy between January 2016 and June 2022 were identified from an institutional database. Survival and recurrence of patients with a cCR who underwent active surveillance were compared with those of patients who underwent planned surgery. Survival was calculated according to the Kaplan-Meier method and compared between groups using the log rank test. RESULTS: The 37 patients who underwent active surveillance were older and tumours were more often located in the middle/upper-third of the oesophagus than in the surgery group of 57 patients. Median follow-up was 28.1 (i.q.r. 17.2-47.1) months for the active surveillance group and 20 (12.9-39.1) months for the surgery group. Overall survival was comparable between the two groups, with 3-year survival rates of 50 (95% c.i. 31 to 67) and 59 (40 to 73)% for the active surveillance and surgery groups respectively (P = 0.55). Three-year progression-free survival for patients who underwent active surveillance was better than in the surgery group: 70 (43 to 85) versus 58 (40 to 72)% (P = 0.02). Overall and progression-free survival was comparable between patients in the active surveillance group and 23 patients in the surgery group who had a pCR (ypT0 N0). The overall recurrence rate was comparable between the groups: 7 of 37 (19.4%) in active surveillance group versus 16 of 49 (32.6%) in surgery group (P = 0.26). Locoregional recurrence was noted more often in the active surveillance group and systemic recurrence in the surgery group. CONCLUSION: Active surveillance is feasible and safe for patients with oesophageal SCC who have a cCR after chemoradiotherapy.

Mathematical explanations for knee osteotomies: "Dear engineer, how would you explain it in a simple way?"

INTRODUCTION: Knee osteotomies are effective procedures to treat different deformities and to redistribute the load at the joint level, reducing the risk of wear and, consequently, the need for invasive procedures. Particularly, knee osteotomies are effective in treating early arthritis related to knee deformities in young and active patients with high functional demands, with excellent long-term results. Precise mathematical calculations are imperative during the preoperative phase to achieve tailored and accurate corrections for each patient and avoid complications, but sometimes those formulas are challenging to comprehend and apply. METHODS: Four specific questions regarding controversial topics (planning methods, patellar height, tibial slope, and limb length variation) were formulated. An electronic search was performed on PubMed and Cochrane Library to find articles containing detailed mathematical or trigonometrical explanations. A team of orthopedic surgeons and an engineer summarized the available Literature and mathematical rules, with a final clear mathematical explanation given by the engineer. Wherever the explanation was not available in Literature, it was postulated by the same engineer. RESULTS: After the exclusion process, five studies were analyzed. For three questions, no studies were found that provided mathematical analyses or explanations. Through independent calculations, it was demonstrated why Dugdale's method underestimates the correction angle compared to Miniaci's method, and it was shown that the variation in patellar height after osteotomy can be predicted using simple formulas. The five included studies examine postoperative variations in limb length and tibial slope, providing formulas applicable in preoperative planning. New formulas were independently computed, using the planned correction angle and preoperatively obtained measurements to predict the studied variations. CONCLUSIONS: There is a strict connection among surgery, planning, and mathematics formulas in knee osteotomies. The aim of this study was to analyze the current literature and provide mathematical and trigonometric explanations to important controversial topics in knee osteotomies. Simple and easy applicable formulas are provided to enhance the accuracy and outcomes of this surgical procedure.

Primary TKA in patients with major deformities and ligament laxities: promising results of an intermediate constrained implant at mid-term follow-up.

BACKGROUND: Total knee arthroplasty (TKA) in major deformities with ligament insufficiency may require a higher constraint, with bone sacrifice and concerns about long-term survivorship. Mid-level constraint liners have been recently introduced, but few studies described their outcomes. The aim of this study is to evaluate the short to mid-term outcomes of a constrained postero-stabilized (CPS) insert for primary TKA in moderate to severe deformities. METHODS: All patients who underwent TKA using a CPS liner in two centers between 2015 and 2017 were included in the study. The indications were: (1) valgus deformity type 2-3 partially correctable; (2) severe varus deformity with varus thrust; (3) post-traumatic deformity with major ligamentous insufficiency and any case of intra-operative ligament insufficiency. Patients were evaluated according to the Knee Society Scoring System (KSS), the Hospital for Special Surgery score (HSS), the Western Ontario and Mc Master University (WOMAC) and the Oxford Knee score (OKS). X-rays were evaluated according to the Knee Society Roentgenographic Evaluation System. RESULTS: Forty-seven TKA were included, with an average age of 66.1 ± 10.3 years and an average follow-up of 68.4 ± 6 months. All patients demonstrated a moderate to severe pre-operative mediolateral instability. All the scores significantly improved (p < 0.0001). In 71.4% of cases, the outcomes were excellent or very good. There were no failures due to aseptic loosening but one failure due to a traumatic ligament rupture. The cumulative survivorship was 97.9% ± 2.1% at 84 months. CONCLUSIONS: This mid-range constraint total knee replacement demonstrated promising outcomes and survival at mid-term follow-up. LEVEL OF EVIDENCE: IV (case series).

The Poncho Lamina Technique: A Protocol for Hard and Soft Tissue Augmentation in Atrophic Ridges Receiving Adjacent Implants.

The current scientific knowledge and guidelines in bone and soft tissue augmentation suggest the use of staged surgical workflows as the gold standard of regenerative procedures during implant therapy. In this context, the process is always the same, regardless of the techniques applied: an alternate series of surgical acts that follow one another after the completion of a specific period of osseointegration or graft maturation. As a result, the overall surgical treatment is often long and invasive and induces scar tissue formation. This article proposes a novel, fast, and less-invasive biphasic protocol with the use of a well-documented cortical barrier mounted on healing screws that are further replaced by customized abutments at an early second stage. Two cases are reported, one for an upper maxillary edentulous area and the other for a mandibular, with a total of four implants placed. The results at 4 months postop showed an optimal soft tissue configuration for both cases, with adequate cervical profile generation and a sufficient supracrestal complex height above the implant platforms. Significant bone gains were also recorded through CBCT data collection, either with alveolar width measurements on axial slices, the superposition of pre-op and post-op datasets, or 3D visualization after bone volume segmentation.

The Use of Nano-Hydroxyapatite (NH) for Socket Preservation: Communication of an Upcoming Multicenter Study with the Presentation of a Pilot Case Report.

Background and Objectives: The use of biomaterials in dentistry is extremely common. From a commercial perspective, different types of osteoconductive and osteoinductive biomaterials are available to clinicians. In the field of osteoconductive materials, clinicians have biomaterials made of heterologous bones at their disposal, including biomaterials of bovine, porcine, and equine origins, and biomaterials of natural origin, such as corals and hydroxyapatites. In recent years, it has become possible to synthesize nano-Ha and produce scaffolds using digital information. Although a large variety of biomaterials has been produced, there is no scientific evidence that proves their absolute indispensability in terms of the preservation of postextraction sites or in the execution of guided bone regeneration. While there is no scientific evidence showing that one material is better than another, there is evidence suggesting that several products have better in situ permanence. This article describes a preliminary study to evaluate the histological results, ISQ values, and prevalence of nano-HA. Materials and Methods: In this study, we planned to use a new biomaterial based on nanohydroxyapatite for implantation at one postextraction site; the nano-HA in this study was NuvaBONE (Overmed, Buccinasco, Milano, Italy). This is a synthetic bone graft substitute that is based on nanostructured biomimetic hydroxyapatite for application in oral-maxillofacial surgery, orthopedics, traumatology, spine surgery, and neurosurgery. In our pilot case, a patient with a hopeless tooth underwent extraction, and the large defect remaining after the removal of the tooth was filled with nano-HA to restore the volume. Twelve months later, the patient was booked for implant surgery to replace the missing tooth. At the time of the surgery, a biopsy of the regenerated tissue was taken using a trephine of 4 mm in the inner side and 8 mm deep. Results: The histological results of the biopsy showed abundant bone formation, high values of ISQ increasing from the insertion to the prosthetic phase, and a good reorganization of hydroxyapatite granules during resorption. The implant is in good function, and the replaced tooth shows good esthetics. Conclusions: The good results of this pilot case indicate starting the next Multicentric study to have more and clearer information about this nanohydroxyapatite (NH) compared with control sites.

Transepicondylar Distance Can Predict Graft and Tunnel Length for Different Pediatric Anterior Cruciate Ligament Reconstruction Techniques: A Magnetic Resonance Imaging Study.

PURPOSE: To find a correlation and mathematical formulas between a linear 2-dimensional (2D) magnetic resonance imaging (MRI) measurement around the knee and the length of the grafts and tunnels required for both all-inside-all-epiphyseal and Kocher-Micheli pediatric anterior cruciate ligament (ACL) reconstruction techniques. METHODS: At time 0 and 30 days after, 2 observers measured: (1) on standard 2D knee MRI, 7 linear distances, representing morphologic measurements, such as transepicondylar distance (TD), and (2) on 3-dimensional (3D) MRI, 5 curved distances, corresponding to Kocher-Micheli and all-epiphyseal ACL reconstruction techniques. Intra- and interobserver reliability was tested for all measurements. The correlation between 2D and 3D measurements was tested. The 2D measurement with highest repeatability and reproducibility and with strongest correlation with 3D measurements was used to extract formulas to calculate the tunnel and graft length for the 2 techniques. RESULTS: Seventy-six MRIs were used. The intra- and interobserver reliability of 2D measurement was high, with TD showing the highest reproducibility and repeatability. 3D measurements also showed good intra and inter-observer reliability. A linear correlation was found between 2D and 3D measurements, with TD showing the strongest correlation. TD was used to extract formulas to calculate graft or tunnel length for Kocher-Micheli and all-epiphyseal ACL reconstruction. All formulas were proven to be accurate. A reference chart was also created to be used in the surgical setting. CONCLUSIONS: With specific formulas, TD can be used to calculate the length of the tunnels, intra-articular portion and graft length for an all-inside all-epiphyseal pediatric ACL reconstruction and the length of the iliotibial band required for the Kocher-Micheli technique. CLINICAL RELEVANCE: The surgeon can use these formulas in pediatric ACL reconstruction preoperative planning, graft harvesting and tunnel drilling.

Transepicondylar distance measured on MRI can predict the length of the graft required for different anterior cruciate ligament reconstruction (ACLR) techniques useful for revision surgery.

BACKGROUND: The aim of this study is to find a correlation between linear measurements and the graft length required for different anterior cruciate ligament (ACL) revision techniques, to extract formulas to predict required graft length during the preoperative planning. METHODS: At time 0 and 30 days later, two observers measured eight linear distances on standard 2D knee magnetic resonance imaging (MRI), and nine curved distances on 3D MRI sequences, corresponding to different techniques for ACL revision, anatomic anterolateral ligament (ALL) reconstruction, and lateral extrarticular tenodesis (LET). Intra- and interobserver reliability was tested for 2D and 3D measurements. The correlation between 2D and 3D measurements was tested. The 2D measurements with highest repeatability and reproducibility, and with strongest correlation with 3D measurements were used to extract formulas to calculate the graft length from 2D values. RESULTS: Fifty MRIs acquired with both 2D and 3D sequences were used. The intra- and interobserver reliability of linear 2D measurement was high, with the transepicondylar distance (TD) showing the highest reproducibility and repeatability. The intra- and interobserver reliability of 3D measurements was lower than 2D, but acceptable for all measurements except for ALL reconstruction. The TD showed the strongest correlation with 3D measurements. The formulas extracted to calculate the graft length from the TD proved to be accurate. CONCLUSION: Accurate formulas were created to calculate the graft length needed for different ACL revision techniques and ALL reconstruction/LET techniques from TD. These formulas can be used during preoperative planning of ACL revision cases.

Visible light mediated synthesis of 6H-benzo[c]chromenes: transition-metal-free intramolecular direct C-H arylation.

A synthetic approach towards the 6H-benzo[c]chromene ring under visible light and transition-metal-free conditions has been developed. Benzochromenes are synthesized from the corresponding (2-halobenzyl) phenyl ethers or (2-halophenyl) benzyl ethers using KOtBu in dimethyl sulfoxide (DMSO) at room temperature (rt) and blue light-emitting diodes (LEDs) as the light source. This methodology replaces the use of ligands or additives, high temperatures and toxic solvents. The photostimulated reaction exhibits very good tolerance to different functional groups and 5H-dibenzo[c,f]chromenes are also effectively obtained. An electron donor-acceptor complex formed by the dimsyl anion and (2-halobenzyl) phenyl ethers was found and it induces the ET as the initial step in the photocyclization reaction. Furthermore, in order to explain the regiochemical outcome of this reaction, a theoretical analysis was performed using DFT methods.

Fractal lacunarity of trabecular bone in vertebral MRI to predict osteoporotic fracture risk in over-fifties women. The LOTO study.

BACKGROUND: Osteoporotic fractures are a major cause of morbidity in the elderly. Menopausal women represent the population with the highest risk of early osteoporosis onset, often accompanied by vertebral fractures (VF). Bone mineral density (BMD) is commonly assessed by dual-energy X-ray absorptiometry (DXA) for osteoporosis diagnosis; however, BMD alone does not represent a significant predictor of fracture risk. Bone microarchitecture, instead, arises as a determinant of bone fragility independent of BMD. High-resolution magnetic resonance imaging (MRI) is an effective noninvasive/nonionizing tool for in vivo characterisation of trabecular bone microarchitecture (TBA). We have previously set up an MRI method able to characterise TBA changes in aging and osteoporosis by one parameter, trabecular bone lacunarity parameter ß (TBLß). Fractal lacunarity was used for TBA texture analysis as it describes discontinuity of bone network and size of bone marrow spaces, changes of which increase the risk of bone fracture. This study aims to assess the potential of TBLß method as a tool for osteoporotic fracture risk. METHODS: An observational, cross-sectional, and prospective study on over-50s women at risk for VF was designed. TBLß, our index of osteoporotic fracture risk, is the main outcome measure. It was calculated on lumbar vertebra axial images, acquired by 1.5 T MRI spin-echo technique, from 279 osteopenic/osteoporotic women with/without prior VF. Diagnostic power of TBLß method, by Receiver Operating Characteristics (ROC) curve and other diagnostic accuracy measurements were compared with lumbar spine DXA-BMD. RESULTS: Baseline results show that TBLß is able to discriminate patients with/without prevalent VF (p = 0.003). AUC (area under the curve from ROC) is 0.63 for TBLß, statistically higher (p = 0.012) than BMD one (0.53). Contribution of TBLß to prevalent VF is statistically higher (p < 0.001) than BMD (sensitivity: 66% vs. 52% respectively; OR: 3.20, p < 0.0001 for TBLß vs. 1.31, p = 0.297 for BMD). Preliminary 1-year prospective results suggest that TBA contribution to incident VF is even higher (sensitivity: 73% for TBLß vs. 55% for BMD; RR: 3.00, p = 0.002 for TBLß vs. 1.31, p = 0.380 for BMD). CONCLUSION: Results from this study further highlight the usefulness of TBLß as a biomarker of TBA degeneration and an index of osteoporotic fracture risk.

Transition-Metal-Free and Visible-Light-Mediated Desulfonylation and Dehalogenation Reactions: Hantzsch Ester Anion as Electron and Hydrogen Atom Donor.

Novel approaches for N- and O-desulfonylation under room temperature (rt) and transition-metal-free conditions have been developed. The first methodology involves the transformation of a variety of N-sulfonyl heterocycles and phenyl benzenesulfonates to the corresponding desulfonylated products in good to excellent yields using only KOtBu in dimethyl sulfoxide (DMSO) at rt. Alternately, a visible light method has been used for deprotection of N-methyl-N-arylsulfonamides with Hantzsch ester (HE) anion serving as the visible-light-absorbing reagent and electron and hydrogen atom donor to promote the desulfonylation reaction. The HE anion can be easily prepared in situ by reaction of the corresponding HE with KOtBu in DMSO at rt. Both protocols were further explored in terms of synthetic scope as well as mechanistic aspects to rationalize key features of desulfonylation processes. Furthermore, the HE anion induces reductive dehalogenation reaction of aryl halides under visible light irradiation.

Incidence and pattern of periprosthetic hip fractures around the stem in different stem geometry.

BACKGROUND: The number of total hip arthroplasties (THA) is expected to increase worldwide; thus, complications are likely to increase at the same ratio. In this scenario, periprosthetic femoral fractures (PFFs) are an increasing concern. Identifying the predisposing factors is important in order to prevent as much as possible the risk of PFF in the future. PATIENTS AND METHODS: The purpose of this study was to correlate the risk of periprosthetic femoral fractures to the most common patients' comorbidities and stem geometry. We reviewed all THA for non-oncologic indications between 2004 and 2014 with a mean follow-up of six years (range, 2-12). Three thousand two hundred forty-eight patients (3593 implants) were enrolled in the study, and 45 PFF were registered during this time period. Two thousand five hundred seventy-seven implants (71%) were straight stems, and 1015 (28.3%) were anatomic stems. All X-rays were then analyzed and classified according to the modified Vancouver classification. RESULTS: Periprosthetic femoral fractures incidence was associated with anatomic stem geometry (p < 0.001, OR = 2.2), BMI (p < 0.001), and diabetes (p < 0.001, OR = 5.18). PFFs were not significantly associated with age, gender, and all the other variables. Fracture pattern was different between straight and anatomic stems. Clamshell fractures were more likely to occur in anatomic stems compared to straight stems (p < 0.005). CONCLUSIONS: Periprosthetic femoral fractures are highly associated with obesity and osteoporosis. Anatomic stems reported a higher incidence of PPF than straight stems. The typical fracture type for anatomical stems is the clamshell pattern, while straight stems are more likely affected by type B fractures.

Total knee arthroplasty in the varus knee: tips and tricks.

Varus knee deformity is very common, and it can be classified according to the severity and reducibility of the deformity. Pre-operative planning is mandatory to obtain a good result. Both clinical and radiological planning should be carefully performed, particularly focused on collateral ligament deficiency. In most of the cases, a postero-stabilized implant is necessary, but in the presence of a varus thrust, a midlevel constrained (MLC) implant may be necessary. Rarely, if a severe extra-articular deformity is present, a femoral osteotomy and a high constrain implant may be necessary. In most of the cases, a standard midline approach can be performed. Soft tissue balancing is crucial, avoiding excessive releases of the medial collateral ligament (MCL). In the presence of severe deformity, more aggressive procedure such as tibial reduction osteotomy or sliding medial epicondyle osteotomy can be performed. In literature, good outcomes are reported for total knee arthroplasty (TKA) in varus deformity. In this manuscript, the available literature on TKA in varus deformity is analyzed, and the preferred surgical techniques of the authors are described.

Protocol and descriptive epidemiology of the SIGASCOT Italian multicentric registry of revision ACL reconstruction: a 1-year pilot study.

The aim of the present study was to present the demographic and baseline results of the first year of course of the SIGASCOT Italian registry of Revision ACL reconstruction.The data of the patients undergoing revision ACL reconstruction, enrolled in by 20 SIGASCOT members from March 2015 to May 2016, were extracted from the Surgical Outcome System (SOS). Overall, 126 patients were enrolled; 18 were excluded due to incomplete data. Mean age at surgery was 30.4 ± 9.3 years (median 29; 23-38), mean BMI was 22.6 ± 2.3 kg/m2 and 77% were males. Revision was performed with a single-bundle technique in 94%, using allograft in 57% of cases and autograft in 43%. Only 28% had both menisci intact, and meniscal repair or replacement was performed in 25% of patients for medial meniscus and 8% for lateral meniscus. During the first year of enrollment, the SIGASCOT Italian ACL revision registry was able to collect the data of more than 100 patients. The revision ACL reconstruction was usually performed with a single-bundle technique, using allograft and autograft almost in the same extent.

Initiation in Photoredox C-H Functionalization Reactions. Is Dimsyl Anion a Key Ingredient?

Previous studies have reported the arylation of unactivated arenes with ArX, base (KOtBu or NaOtBu), and an organic additive at high temperatures. Recently, we showed that this reaction proceeds in the absence of additives at rt but employs UV-vis light. However, details of mechanisms that can use a photoinduced base-promoted homolytic aromatic substitution reaction (photo-BHAS) have remained elusive until now. This work examines different mechanistic routes of the essential electron-transfer step (ET) of this reaction in order to identify a possible path for the formation of 1-adamantyl radicals from 1-haloadamantanes (initiation step). On the basis of photochemical and photophysical experiments and computational studies, we propose an unprecedented initiation step that could also be applied to other ET reactions performed in DMSO. For the first time, it is reported that dimsyl anion, formed from a strong base and DMSO (solvent), is responsible for inducing the initiation by a photo-BHAS process on alkyl halides.

Subclinical hypothyroidism and diabetes as risk factors for postoperative stiff shoulder.

PURPOSE: Postoperative stiffness can be a disabling condition after arthroscopic shoulder surgery. The purpose of this study was to analyse the potential contribution of subclinical forms of hypothyroidism and diabetes in the development of postoperative shoulder stiffness. METHODS: A prospective study was conducted on 65 consecutive patients scheduled for arthroscopic subacromial decompression or rotator cuff tear repair. Patients with preoperative stiffness were excluded. Preoperative measurements of free thyroxine, free triiodothyronine, thyroid-stimulating hormone and fasting glycaemia were taken in all patients to detect subclinical forms of diabetes and hypothyroidism. A follow-up was planned at 30, 60, 90 and 180 days after surgery. According to range of motion measurements, postoperative stiffness was classified as severe or moderate at follow-up. Univariate and logistic regression analyses were performed for the assessment of risk factors for stiffness. RESULTS: The overall incidence of postoperative stiffness was 29 % (19/65) in our cohort. Considering only the arthroscopic rotator cuff repairs, this incidence was 23 % (7/31). A new diagnosis of subclinical forms of diabetes or hypothyroidism was made in five cases. All five of these cases developed postoperative stiffness. The logistic regression analysis demonstrated that hypothyroidism was a risk factor for severe stiffness (RR = 25; p = 0.001) and that diabetes was a risk factor for moderate stiffness (RR = 5.7; p = 0.03). CONCLUSION: The postoperative stiffness in the majority of patients can be predicted by a careful analysis of past medical history and by detecting subclinical forms of hypothyroidism and diabetes. LEVEL OF EVIDENCE: Prognostic study, Level II.

Fusion of the First Metatarsophalangeal Joint and Second to Fifth Metatarsal Head Resection for Rheumatoid Forefoot Deformity.

The goals of the present study were to evaluate the mid-term results of first metatarsophalangeal joint fusion combined with second to fifth metatarsal head resection in rheumatoid forefoot deformity and identify the prognostic factors. The inclusion criteria were 2010 American College of Rheumatology and/or European League Against Rheumatism criteria for rheumatoid arthritis; symptomatic forefoot deformity; first metatarsophalangeal joint fusion and second to fifth metatarsal head resection; and a minimum of 4 years of follow-up data available. The patients were evaluated using the Disease Activity Score 28 for rheumatoid arthritis, Health Assessment Questionnaire for Rheumatoid Arthritis, Foot Function Index, forefoot American Orthopaedic Foot and Ankle Society scale, and weightbearing radiographs. Different pre-, intra-, and postoperative variables were investigated to identify the prognostic factors. Sixty-two patients (89 feet) with a mean age of 60.8°± 9.4 years and 85.5°± 22.4 months of follow-up data were included. The preoperative American Orthopaedic Foot and Ankle Society scale score was 33.4 ± 16 points and improved significantly (p < .001) after surgery (mean 82.9 ± 11.7 points). The mean Foot Function Index improved significantly (p < .001) from 131.6 ± 37.4 to 77.4 ± 46.3 points at the last follow-up visit. Only the revision surgery variable was significantly (p = .02) related to poor outcomes. Revision was necessary in 8 feet (9%). This procedure produced satisfactory results. Poor outcomes were significantly related to the necessity for revision surgery for nonunion, malunion, inadequate metatarsal resection, and painful hardware.

Synthesis of Dibenzosultams by "Transition-Metal-Free" Photoinduced Intramolecular Arylation of N-Aryl-2-halobenzenesulfonamides.

A new and general synthetic route to prepare dibenzosultams is here reported. This approach involves the synthesis of N-aryl-2-halobenzenesulfonamides (3), followed by intramolecular C-C photoinduced arylation under soft conditions without the use of "Transition Metal". The photostimulated reactions exhibit very good tolerance to different substituent groups with good to excellent isolated yields (42-98%) of products. Moreover, it is shown that LED (λ = 395 nm) is an efficient light energy source to initiate efficiently the reactions. Theoretical inspection of the mechanism was made to probe the involvement of the radical-anion SRN1 process.