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Unanticipated formation of symmetrical sulfonyl guanidine was observed while treating isonitriles with N,N-dibromoarylsulfonamides in absence of an external amine source. Interesting feature of this work is that one molecule of isonitrile initially reacts with dibromoarylsulfonamide via the C-end to produce the intermediate carbodiimide while the other molecule undergoes C≡N triple bond cleavage to react as amine source with the intermediate. This switch of reactivity from C-center to N-center of the isonitrile generated symmetrical guanidine.

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A cascade protocol for the synthesis of aminotetrazoles have been developed by treating isonitriles, N,N-dibromoarylsulfonamides, and sodium azides in the presence of K2CO3. This metal-free process proceeds via an isolable carbodiimide intermediate at room temperature, which could further react with sodium azide and subsequently cyclizes intermolecularly to provide 5-aminotetrazoles within a short reaction time. The present protocol's remarkable achievements are the wide substrate scope, good to excellent yields, and good functional group tolerance.

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Introduction: Melorheostosis was initially identified in 1922 by Leri and Joanny. It is often referred to as candle bone disease, melting wax syndrome, or Leri disease. This mesenchymal condition is uncommon, benign, and non-heritable. There is still a lack of clarity regarding the underlying cause of the condition. The estimated incidence is 0.9% per million. No inherited traits have been identified, and both sexes are equally affected. Pain or swelling is the most typical symptoms, and the onset is insidious. People often call this condition "candle disease of the bone" because the radiological signs of it look like dripping candle wax. Case Report: A 56-year-old female presented with an 8-year history of the left knee pain, swelling, and movement restriction. On examination, a hard, bony lump measuring 12×5 cm was located on the outer aspect of the left knee. The skin over the lump's surface was neither erythematous nor warm. Plain radiographs revealed a wide, dense, undulating, or irregular cortical hyperostosis, resembling candle wax, spreading along the length of the fibula bone as well as an extra-osseous calcification mass across the lateral aspect of the left knee. The patient underwent excision with complete left knee motion. Conclusion: Melorheostosis' actual etiology is yet unknown. There is no established treatment for this condition. Only symptomatic treatment helps patients feel better; in some circumstances, the excision of a bone mass yields more beneficial results.

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An efficient protocol for the synthesis of cyclic guanidine with exocyclic double bond has been developed. The synthesis has been achieved via intramolecular hydroamination of an intermediate propargyl guanidine by using silver acetate as catalyst in the presence of acetic acid. The reaction proceeds via the formation of acyclic propargyl guanidine in a one-pot reaction of N,N-dibromoarylsulfonamides, isonitriles, and propargylamine in the presence of K2CO3. In the second stage of the synthesis, the acyclic guanidine selectively undergoes 5-exo-dig cyclization in the presence of silver acetate and acetic acid to produce the five-membered cyclic guanidine framework having an exocyclic double bond as the constituent part. Short reaction time, wide substrate scope with good to high yields, and good functional group tolerance are the remarkable achievement of the present protocol.

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BACKGROUND: Treatment for osteoporosis can have catastrophic side effects, including the uncommon fracture known as an atypical femur fracture (AFF), which is related to the long-term usage of antiresorptive agents. Bisphosphonate therapy may lead to significant and chronic suppression of bone turnover, impairing the bone's remodelling property and finally leading to incomplete or complete atypical femur fracture. AFF was defined by the American Society for Bone and Mineral Research (ASBMR) Task Force in 2010 and is far less prevalent than proximal femur (hip) fracture, with an incidence of 2 to 78 per 100,000 patients per year following two to eight years of bisphosphonate therapy, respectively. Due to the rarity of the fracture, it is still not clear what the functional and radiological outcome will be after surgery. AIM: To identify the functional and radiological outcomes of surgical fixation of atypical femur fractures. METHODS: The study was conducted in a tertiary healthcare centre after scientific and ethical clearance from the competent authority. Between January 2018 and December 2021, individuals who were diagnosed with an atypical subtrochanteric femoral fracture associated with the use of bisphosphonates and treated surgically were retrospectively evaluated. The study's inclusion and exclusion criteria were used to include 20 patients. The features of an atypical subtrochanteric fracture were congruent with the radiographic findings. Most of the patients were treated with internal fixation with intramedullary osteosynthesis in standard with or without plate osteosynthesis. They were then followed up for a year to look at the functional and radiological outcomes. RESULTS: All of the 20 patients who were included had an atypical subtrochanteric fracture, with 15 of them being female and 5 of them being male. The patients' mean age at surgery was 65.12 (range 49 to 82) years, and their average history of bisphosphonate use was 3 (range 2.5 to 5) years. All patients were treated surgically. We found that five months was the mean period for bone union (p = 0.990). Within six months, bone union was achieved in 11 patients (55 %) (p = 0.884). Five patients (about 25%) had implant failure and non-union, requiring two to three revision surgeries. At three, six, and nine months, the mean visual analogue score (VAS) was 4.14, 3.12, and 1.85, respectively. The modified Hip Harris Score had a mean of 72.66 and 15 patients (about 75% of them) could walk normally again after a fracture. The mean of the modified HHS was 72.66, and the VAS at three, six, and nine months was 4.14, 3.12, and 1.85, respectively. CONCLUSION: AFFs are rare fractures that must be treated effectively, and most of them require surgery. Successful treatment of AFF is possible by the use of intramedullary fixation, which enhances axial stability, serves as an internal splint, and lessens the likelihood of implant failure. A good functional and radiological prognosis can come from a stable fixation and a fracture that has been reduced anatomically.

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A unified approach has been developed for the synthesis of both isourea and isothiourea in a three-component coupling reaction by treating alcohols or thiols respectively with N,N-dibromoarylsulfonamides and isonitrile and in the presence of K2CO3. This metal-free process proceeds via carbodiimide intermediate at room temperature within a very short reaction time. A library of sulfonylisoureas and isothioureas has been made using this synthetic protocol with wide substrate scope in good to high yields.

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Giant cell tumors (GCTs) are primary bone tumors that occur most commonly in long bones, with half such tumors occurring in the distal femur, proximal tibia, and fibula. Around 12% of patients present with a pathological fracture indicating more aggressive disease. Arthrodesis after tumor resection is a popular choice due to its affordability and early postoperative mobilization, as well as low risks of implant loosening, infections, malignant lesions, or mortality. A free fibular graft is a popular option in limb-sparing surgery for long bone tumors. A bone graft and nail can be used to reconstruct long bones and bridge defects up to 25 cm. In developing countries, the cost of the imported mega prosthesis, around 8,500 US$, means many patients cannot afford the treatment. We describe a case of a GCT of the distal femur treated by excision of the tumor and reconstruction using a fibular bone graft, with knee arthrodesis using a custom-made long intramedullary interlocking nail fixation across the femur to the knee and the tibia. The length was achieved with 1 cm shortening post-surgery. The result was satisfactory, and partial weight-bearing was allowed three months after the surgery. At the one-year follow-up, there was no recurrence, and the patient had the full weight-bearing ability.

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OBJECTIVE: The spectrum of vascular involvement in systemic sclerosis (SSc) includes digital ulcers, gangrene, Raynaud's phenomenon, renovascular disease, and pulmonary hypertension (PH). Recognition of markers of subclinical vascular disease in SSc is an area of active research, but such studies are limited. This study assesses the role of measurement of the renal resistive index (RRI) as an early marker of renal and systemic vasculopathy. It is a step forward towards examining the possibility of a "unified vascular phenotype' in SSc. METHODS: In this single-centre prospective study, RRI was calculated for SSc patients >18 years age. Elevated RRI (>0.7) was correlated with renal function (eGFR and proteinuria) and systemic vasculopathy manifestations like digital ulcers, digital infarcts, and PH. RESULTS: A total of 73 patients with mean (SD) age 41.8(10.9) years were included. Mean (SD) RRI in the right and left renal artery was 0.65(0.08) and 0.66(0.07), respectively. 16 (21.9%) patients had elevated RRI (>0.7). A strong negative correlation was noted between elevated RRI and eGFR (r= -0.96, p=0.03). The percentage of patients with overt proteinuria was higher in the group with elevated RRI (20% versus 7%) (p=0.16). Similarly, digital ulcers (56% vs 33%) and digital pitting (50% vs 35%.) were numerically higher in the group with raised RRI, although statistical significance was not reached because of small numbers (p=0.09 and 0.28, respectively). No correlation of RRI with PH was identified. CONCLUSION: RRI correlates well with asymptomatic renal dysfunction and holds promise in the assessment of systemic vasculopathy. However, validation in studies with a larger sample size is needed.

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OBJECTIVES: To evaluate the efficacy and safety of a step-down regimen of oral prednisolone over 24 weeks in patients of axial SpA (axSpA). METHODS: This proof-of-concept double-blind randomized controlled trial enrolled patients with active axSpA (BASDAI ≥4) having predominantly axial disease (≤1 active joint currently) and inadequate response to NSAIDs. They were randomized to receive either oral prednisolone (n = 32) or placebo (n = 33) at a dose of 60, 40, 30, 20, 15 and 10 mg daily for 1 week each, following which they received 5 mg prednisolone (or placebo) daily for 18 weeks. The primary endpoint was a 50% improvement in the BASDAI (BASDAI50) at week 24. Analysis was intention to treat. RESULTS: A BASDAI50 was achieved by 12 of 32 patients (37.5%) in the prednisolone arm and 3 of 33 patients (9.1%) in the placebo arm at 24 weeks [difference 28.4% (95% CI 7.9, 46.7)]. However, there was no difference in achieving a 20 or 40% improvement in the Assessment of SpondyloArthritis international Society response between the groups. Although there was a significant intergroup difference in adjusted ΔBASDAI and ΔAnkylosing Spondylitis Disease Activity Score with CRP at 24 weeks, there was no difference at 12 weeks. There was also no significant difference in ΔBASFI, ΔBAS-G or ΔBASMI at 12 or 24 weeks. No serious adverse events were noted. There was significant weight gain in the first 12 weeks in the prednisolone group vs placebo [0.9 (s.d. 0.4) kg], but not at 24 weeks. CONCLUSIONS: In this small study, oral prednisolone was efficacious in axSpA in achieving the primary outcome, but many crucial secondary outcomes such as functional improvement were not met. Its impact on bone loss was not studied.Trial registration: CTRI/2018/01/011342.

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AIM: The aim of this study was to evaluate whether there is any consistent relationship between interalar distance and six maxillary anterior teeth in two ethnic groups. MATERIALS AND METHODS: Two hundred subjects (Assamese 100 and Nyishi 100) of different age and sex ranging from 18 to 33 years were identified for this study. The distance between two widest points marked on the alae of nose was measured by means of sliding digital caliper. Statistical analysis of variance was the testing method to determine whether the nasal width and intercanine distance were different in various racial groups. RESULTS: The mean nasal width dimension in Assamese group was 36.38 mm (range 28.55-50.00 mm). The mean nasal width dimension in Nyishi group was 35.73 mm (range 31.34-41.90 mm). For the nasal width, no significant difference was observed between two races. For the canine cusp tip to cusp tip distance, the mean value of Assamese subjects was 43.63 mm (range 39.02-50.02 mm), whereas the Nyishi presented 41.77 mm (range 36.69-47.05 mm). CONCLUSION: For the two racial groups studied, the measurements of the interalar width showed a weak correlation with the canine to canine distance, not sufficiently high to be used as a predictive factor. It suggests to select wider artificial teeth. Practitioners can use ethnic norms as guides, not absolute values.

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INTRODUCTION: Unicompartmental knee arthroplasty (UKA) is a procedure used to treat isolated medial or lateral compartmental osteoarthritis of the knee joint. This procedure involves retention of cruciate ligaments which leads to better functional outcome due to preservation of normal kinematics of the knee joint. In the Indian population, due to requirement of squatting and cross leg sitting habits, knee with more range of movement and with good kinematics is a required feature. The study aims to observe the functional outcome, mortality, revision rate, length of hospital stay and satisfaction rate in two-year postoperative patients in a tertiary health care centre. METHODS: A total of 17 knees of 15 patients were recruited for the study after applying strict inclusion and exclusion criteria. These patients were operated during the period from March 2015 to March 2018. Ten female patients (67%) and five males (33%) were included. The average age was 61 years. All operations were performed by a single surgeon, with a similar implant from a single company. Similar protocol was used both for surgical technique (minimal invasive) and postoperative rehabilitation for all the patients. RESULTS: The functional outcome in the form of Oxford Knee Score (OKS) and Euro-Quol (EQ-5D) scores improved significantly in all the patients at one year postoperatively, and the improvement remained significant for two years. Satisfaction rate was 91.7% (SD-12.8) at two years. Except for one patient (5.8%), all patients were able to cross leg and squat easily. At the end of two years, the overall survival rate of the implant was found to be 94.1%. CONCLUSION: The unicondylar arthroplasty provides excellent satisfaction to the appropriately selected patients with good survivorship of implant. It can be a surgery of choice for Indian population as it restores normal kinematics of knee joint and allows the patient to cross leg and squat with a more range of movement.

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An unprecedented 1,3-migration of the tert-butyl group was observed while reacting tert-butyl isonitrile with N,N-dibromoaryl sulfonamides and nitrile. The reaction involves the simultaneous C-N single bond scission of isonitrile and the migration of the tert-alkyl group to the adjacent unsaturated nitrogen centre of the nitrile precursor, which eventually results in the formation of N-sulfonyl amidine. This method constitutes a new route for sulfonyl amidine, which does not rely on transition metals. The protocol exhibits a significant advantage in terms of substrate scope and additionally offers an easy synthesis route to guanidine molecules.

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To assess the efficacy and safety of pirfenidone in systemic sclerosis-related interstitial lung disease (SSc-ILD). This was a double-blind, randomised, placebo-controlled, pilot study. Subjects with SSc-ILD and forced vital capacity (FVC) between 50 and 80% of the predicted (%pred) value were randomised in 1:1 ratio to receive either pirfenidone (2400 mg/day) or placebo for 6 months. Primary outcome was the proportion of subjects with either stabilisation or improvement in FVC at 6 months. Secondary outcomes were the absolute change in the %pred FVC, Mahler's dyspnoea index, 6-min walk distance (6MWD), modified Rodnan skin score (MRSS) and serum levels of tumour necrosis factor α (TNF-α) and transforming growth factor ß (TGF-ß). Thirty-four subjects with median (range) age of 41 (20-63) years (91.2% women) and median (range) %pred FVC of 65 (51-78) were enrolled. Stabilisation/improvement in FVC was seen in 16 (94.1%) and 13 (76.5%) subjects in the pirfenidone and placebo groups, respectively (p = 0.33). The median (range) absolute change in %pred FVC was - 0.55 (- 9 to 7%) and 1.0 (- 42 to 11.5%) in the treatment and control groups, respectively (p = 0.51). The changes in 6MWD, dyspnoea scores, MRSS, and levels of TNF-α and TGF-ß were not significantly different between groups. Common adverse events were gastrointestinal disturbances and skin rash. We failed to find a significant beneficial effect of pirfenidone over placebo in improving/stabilising FVC, exercise capacity, symptoms, or skin disease. Study is underpowered to provide conclusive evidence. Larger studies with longer follow-up periods are required.

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