Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled study.

Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13-22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.

Cement beads and cement spacers: indications, techniques, and clinical results.

Objectives: To report our experience on the use of antibiotic coated nails (ACN) and cement beads for the management of bone infections. Materials and methods: Infected nonunion (INU) cases were classified as: Type I (mild infection with no gap), Type II (moderate with good alignment, severe infection, gap <3 cm, no deformity), Type III (severe infection with gap ≥3 cm, deformity and limb shortening). Treatment involved either the insertion of ACN and cast (Type I), insertion of ACN, beads and external fixator (Type II), or Ilizarov methodology (Type III). A subset of 28 open fractures were admitted with severe contamination or delayed presentation with established infection and treated with debridement, ACN insertion, and antibiotic beads placed in soft tissue dead space areas. Results: Results of 133 cases were classified excellent, good, and poor. Type I INU reported 40 excellent and 22 good results. Type II INU reported 28 (39%) excellent, 30 (43%) good, and 13 (18%) poor results. Poor results were due to uncontrolled infection and knee stiffness. Three patients required knee fusion and 1 required amputation. Fracture union was reported in 68 cases. Four of the 28 Gustilo grade III open fractures treated with ACN developed infected nonunion and had poor function caused by stiff knees. Conclusions: An antibiotic impregnated cement nail (ACN) fills the dead space and elutes high concentrations of antibiotics providing some mechanical stability. We recommend the adjunct use of an ACN for the management of INU cases and for use in select cases of Gustilo grade III open fractures.

Evolocumab in patients with homozygous familial hypercholesterolemia in India.

BACKGROUND: Evolocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 approved in India for treatment of homozygous familial hypercholesterolemia (HoFH) in patients aged ≥12 years. OBJECTIVE: RAMAN (NCT03403374) was a single-country, open-label, phase 4 study evaluating the safety and tolerability of evolocumab in patients with HoFH in India. METHODS: Patients ≥12 to ≤80 years of age on stable lipid-lowering therapy with fasting low-density lipoprotein cholesterol (LDL-C) >3.4 mmol/L (>130 mg/dL) received evolocumab 420 mg subcutaneously monthly (every 2 weeks if on apheresis). The primary endpoint was patient incidence of treatment-emergent adverse events. Secondary endpoints included percent changes at week 12 in LDL-C and other lipids. RESULTS: Of 30 enrolled patients, 13 were <18 years of age. Mean±SD baseline levels of LDL-C, apolipoprotein B, and lipoprotein(a) were 12.3 ± 3.5 mmol/L (473.5 ± 135.2 mg/dL), 2.8 ± 0.7 g/L (275.3 ± 69.1 mg/dL), and 201.3 ± 177.6 nmol/L, respectively. Ten patients (33%) reported treatment-emergent adverse events, with 2 (7%) serious adverse events and none leading to discontinuation; no deaths occurred during evolocumab treatment. At week 12, mean (SE) percent changes from baseline in LDL-C, apolipoprotein B, and lipoprotein(a) were -6.4% (4.2), -6.0% (3.7), and -0.2% (4.9), respectively. Reductions in LDL-C among individual patients were variable and greatest in patients ≥18 years of age and with baseline LDL-C <13 mmol/L (<500 mg/dL). CONCLUSIONS: Evolocumab was safe and well tolerated in patients with HoFH in India with smaller reductions in LDL-C and other lipids than those observed in previous studies with HoFH and different populations.

Augmentation of intramedullary nailing in unstable intertrochanteric fractures using cerclage wire and lag screws: a comparative study.

BACKGROUND: Unstable intertrochanteric fractures present a challenge to orthopaedic surgeons, with varied geometry of the fractures and a wide choice of implants and techniques. The patients are usually osteoporotic, with multiple co-morbidities and poor tolerance for complications and re-operations. Lateral wall reconstruction and stability of the trochanteric fragments are considered important in providing a better outcome of these difficult injuries. We present a technique of lateral wall and trochanteric reconstruction using Cerclage wires and lag screws in the greater trochanter in addition to intramedullary nailing, and the radiological and functional outcome of this technique of augmentation. MATERIALS AND METHODS: This prospective study includes 154 patients from 2010 to 2015 presenting to the institute with an unstable intertrochanteric fracture. They were sequentially operated with intramedullary nailing (IMN) and augmentation with cerclage wire and/or Anteroposterior screw in greater trochanter, and 77 patients with IMN only. Operating time and need for blood transfusion post-surgery were documented. Patients were followed up for minimum of 12 months and radiological union time, complications and functional outcome using Harris Hip Score were noted at 1 year. Statistical analysis was performed to compare the results in both groups RESULTS: The mean union was 3.6 months in group A and 4.1 months in group B, with no statistically significant difference. The operating time needed for augmentation was 10 minutes more than IMN only. Blood transfusion was not required in any case. The incidence of complications like screw cut out, back out and non-union was lower in augmented group, and good functional outcome was greater in the augmented group which was statistically significant. The reoperation rate was lower in augmented group. CONCLUSIONS: This new technique of augmentation of fixation of intramedullary nail in unstable trochanteric fractures using cerclage wires and lag screws for lateral wall reconstruction is useful in reducing complications of the procedure and provides good radiological and functional outcome. It requires little additional operating time with minimal blood loss and soft tissue injury.

Comparison between antegrade intramedullary nailing (IMN), open reduction plate osteosynthesis (ORPO) and minimally invasive plate osteosynthesis (MIPO) in treatment of humerus diaphyseal fractures.

INTRODUCTION: The three currently used methods of treatment: namely open reduction plate osteosynthesis (ORPO), Minimally invasive plate osteosynthesis (MIPO), antegrade intramedullary nailing(IMN) are all reported as satisfactory procedures for treatment of humeral shaft fractures. However none of the published reports have a comparison of superiority of one procedure over the other. We evaluated the clinical, radiological and functional outcome of the three procedures. MATERIALS AND METHODS: We studied adult patients with humerus shaft fractures over a period of 2 years from May 2014 to May 2016 in a level 1 trauma center. Forty-four were treated with IMN, 34 treated with ORPO, and 34 with MIPO. The null hypothesis tested in this study is that there is no difference between IMN, ORPO, MIPO with respect to union time, surgical time, complication rate, non-union rate and functional outcome. Functional outcome was studied by comparing the UCLA shoulder and MEP scores in the three groups. RESULTS: 112 patients were studied consisting of 83 males and 29 females with mean age of 39 years (range 18-70). IMN group showed early union with mean of 12.73 weeks compared to MIPO (14.45 weeks) and ORPO(13.58 weeks), (p<0.05). MIPO had no events of non-union, as compared to ORPO (5 non-unions) and IMN (10 non-unions), (p=0.04). The range of movement at the shoulder with the UCLA score was significantly better with a score of 32.26 in MIPO as compared to 27.54 in IMN and 28.82 in ORPO (p<0.05). The difference in MEPS score in the three groups was not significant (p=0.31). IMN required a mean of 117.95 minutes intraoperatively as compared to 131 and 150.58 mins in MIPO, ORPO respectively. CONCLUSION: MIPO is overall better with respect to non-union, functional outcome and complications rate. The surgical time depends on the surgeons' skill and learning curve. Thus considering the advantages and risks involved in the various procedure and surgical acumen, each case should be individualized to have a good outcome. We advocate that MIPO can be safely used as an alternative in treating these fractures.

Limb lengthening over plate.

BACKGROUND: The limb lengthening over plate eliminates the associated risk of infection with limb lengthening over intramedullary nail. We present our experience of limb lengthening in 15 patients with a plate fixed on the proximal segment, followed by corticotomy and application of external fixator. MATERIALS AND METHODS: 15 patients (7 females, 8 males) were included in this consecutive series. The average age was 18.1 years (range 8-35 years). Fifteen tibiae and one femur were lengthened in 15 patients. Lengthening was achieved at 1 mm/day followed by distal segment fixation with three or four screws on reaching the target length. RESULTS: The preoperative target length was successfully achieved in all patients at a mean of 4.1 cm (range 1.8-6.5 cm). The mean duration of external fixation was 75.3 days (range 33-116 days) with the mean external fixation index at 19.2 days/cm (range 10.0-38.3 days/cm). One patient suffered deep infection up to the plate, three patients had mild procurvatum deformities, and one patient developed mild tendo achilles contracture. CONCLUSION: Lengthening over a plate allows early removal of external fixator and eliminates the risk of creating deep intramedullary infection as with lengthening over nail. Lengthening over plate is also applicable to children with open physis.

Antegrade interlocking nailing versus dynamic compression plating for humeral shaft fractures.

PURPOSE: To compare antegrade interlocking nailing with dynamic compression plating for humeral shaft fractures in terms of functional outcomes, union and complication rates. METHODS: 34 men and 22 women aged >18 years with fresh humeral shaft fractures (up to grade IIIa) with or without neurological deficits underwent either antegrade interlocking nailing (n=31) or dynamic compression plating (n=25). Functional outcome of the upper limbs (according to the American Shoulder and Elbow Surgeons [ASES] score), pain, rates of union, and complications in the 2 groups were compared. RESULTS: Respectively in the nailing and plating groups, mean operating times were 65 and 112 minutes (p<0.001), mean blood loss volumes were 20 and 232 ml (p<0.001), mean ASES scores were 31.4 and 29.0 (p=0.448), complication rates were 20% (6/31) and 24% (6/25) [p=0.900], non-union rates were 13% (4/31) and 8% (2/25) [p=0.625], and delayed union rates were 7% (2/31) and 4% (1/25) [p=0.787]. CONCLUSION: Both techniques were appropriate for treating humeral shaft fractures.

Intramedullary nailing supplemented with Poller screws for proximal tibial fractures.

PURPOSE: To evaluate outcome of intramedullary nailing supplemented with Poller screws for proximal tibial fractures using small diameter nails. METHODS: 50 men and 20 women (75 fractures) aged 18 to 65 (mean, 33) years underwent intramedullary nailing supplemented with Poller screws for acutely displaced fractures (n=60) or for delayed union (n=10) or mal-union (n=5) of the proximal metadiaphyseal tibia. 88% of the fractures were caused by road traffic accidents. 54 cases had closed fractures and 21 had grade I or II compound fractures. Clinical and radiological outcome was evaluated. RESULTS: In 69 cases, healing occurred after a mean of 4.2 (range, 3-9) months. In 5 cases, there was non-union, which was resolved by bone grafting. One case was mal-united. 63 patients recovered a full range of knee motion (0º-130º), and the remaining 7 attained flexion of 0º to 90º. According to the knee rating scale of the Hospital for Special Surgery, outcome was excellent in 50 patients, good in 14, poor in 3, and failed in 3 at month 12, and remained so after a mean follow-up of 30.8 months. Postoperatively, 74 cases had <5º of varus or valgus malalignment, and only one developed varus of +7º. 65 cases exhibited no deformity, 7 had a deformity of <3º, and 3 had a deformity of 4º to 9º. CONCLUSION: Poller screws help maintain fixation of intramedullary nailing and alignment of fractures.

Antegrade interlocking nailing for distal femoral fractures.

PURPOSE: To assess outcomes of antegrade interlocking nailing for supracondylar or intercondylar fractures of the distal femur. METHODS: Records of 10 women and 20 men aged 20 to 70 (mean, 48.7) years who underwent antegrade interlocking nailing for distal femoral fractures were reviewed. 23 patients had closed fractures and 7 had open fractures; 6 had associated fractures of the forearm or tibia. According to the AO/ASIF system, fractures were classified as types A1 (n=13), A2 (n=6), A3 (n=3), and C1 (n=8). The affected leg was put in an extension shoe for traction, and reduction was achieved with the help of percutaneous lag screws. The nail was inserted from the tip of the greater trochanter and centred in both anteroposterior and lateral planes. The nail was modified to have 3 screw slots in the mediolateral plane and one screw slot in the anteroposterior plane distally for stability in multiple directions. Postoperatively early mobilisation and partial weight bearing were allowed. Patients were assessed using the modified knee-rating scale of the Hospital for Special Surgery. RESULTS: The mean time to bone union was 13.1 (range, 10-18) weeks. The mean follow-up period was 18.8 (range, 11-30) months. Three patients were lost to follow-up; outcomes in the remaining patients were excellent in 20 and good in 7. The mean range of knee flexion was 106 (range, 90-120) degrees. One patient developed a flexion deformity of 10 degrees. All patients attained full quadriceps strength. No patient had ligamentous instability, nerve injuries, superficial or deep infections, or implant failure. Three patients had malunion, which was located in the meta-diaphyseal segment and not in the intraarticular segment. Hence, there was no functional problem or shortening. The mechanical axis was not deviated. CONCLUSION: Antegrade interlocking nailing achieved good-to-excellent outcomes for distal femoral fractures.

Textiloma in the leg.

Textiloma is defined as a tumor formed due to retained gauze. It is rarely reported in the musculoskeletal system. We are presenting a case with a soft tissue swelling over the lateral aspect of the lower third of the leg, come for implant removal of the distal tibia and fibular fracture. We removed the soft tissue mass enbloc thinking it to be a benign tumor. On cutting the mass on the operation table, a gauze piece encased by fibrous tissue was found. Textiloma can present as tumoral forms and can mimic as a pseudo-tumor.