Open reduction for hip dislocation in children with arthrogryposis multiplex congenital: Outcomes of a systematic review.

Introduction: The incidence of hip dislocation (HD) in arthrogryposis multiplex congenital ranges from 15 to 30 %. Besides a stable hip, the ambulation potential of an AMC child is also dependent on severity of associated knee and foot deformations. The primary objective of this review is to determine the proportion of ambulators in AMC children treated by open reduction for HD. Methods: We searched major electronic bibliographic databases for reports on the treatment of HD among AMC children. Based on the surgical approach for open reduction of HD in AMC children, we divided the included studies into groups 1 (Anterior approach open reduction) and 2 (Medial approach open reduction). Results: We pooled 59 children/94 hips in this review from 7 studies. We identified 45 children/71 hips and 14 children/23 hips with a mean age of 20 (4-64) and 4.5 (0.5-11) months in groups 1 and 2, respectively. There were 97 % (44) and 92 %(Obeidat et al., 2011) 13 ambulators in groups 1 and 2, respectively. 47 % and 36 % of hips in groups 1 and 2 required additional procedures besides open reduction for redislocation and maintenance of hip reduction. 31 %22 and 13 %(Fisher et al., 1970 Feb) 3 of the hips sustained avascular necrosis in group 1 and 2. Conclusion: Children with AMC associated HD can be expected to ambulate with and without assistance in 90 % of the cases however, the foot and knee problems also need concomitant management. In children less than 6 months of age the medial approach based open reduction may be more efficacious and less complicating than anterior approach based open reduction however, at a later age anterior approach based open reduction is more effective due to need for pelvic and femur sided additional procedures.

Latarjet operation carries three times the risk of failure in seizure versus non-seizure recurrent anterior dislocation of the shoulder joint: outcome of a systematic review with meta-analysis.

BACKGROUND: Recurrent anterior shoulder dislocation (RASD) in cases of seizure disorders (SDs) total 50%-80% of all SD-associated shoulder instabilities. Based on the extent of bone loss, treatment options include bony and soft-tissue reconstructions, arthroplasty, and arthrodesis. The primary objective of this paper was to review the treatment options for RASD in SDs. METHODS: Several bibliographic databases were searched for RASD treatment options in SD patients. The demographic outcome measures, the failure rate (defined as the relative risk of recurrence of dislocation postoperation), and the postoperative seizure recurrence rate were recorded. RESULTS: We pooled 171 cases (187 shoulders) from 11 studies. Of these, one, five, two, two, and one reports studied Bankart's operation with remplissage (27 cases/29 shoulders), the Latarjet procedure (106/118), bone block operation (21/23), arthroplasty (11/11), and arthrodesis (6/6), respectively, in treating SD-associated RASD. The relative risk of failure between SD and non-SD patients was 3.76 (1.3610.38) after the Latarjet operation. The failure rates were 17% and 13% for Bankart's operation with remplissage and the Latarjet procedure in SD patients, respectively, but 0% each for bone block operation, arthroplasty, and arthrodesis. The total rate of seizure recurrence after operation was 33% of the pooled cases. CONCLUSIONS: SD recurrence in the postoperative period, the size of the bone block, and the muscular attachments to a small coracoid autograft are the determinants of failure among various reconstructive operations in SD-associated RASD. Level of evidence: III.

Ultrasound-Guided Manipulation does not Prevent Malalignment Over Landmark-Based Fracture Reduction in Distal Radius Fracture (Colles).

Introduction: This systematic review aims to determine the relative risk of distal radius (Colles) fracture (DRF) malalignment between ultrasound (USG)-guided and conventional/landmark guided/blind manipulation and reduction (M&R). Methods: We searched 3932 records from major electronic bibliographic databases on USG-guided manipulation of DRF. Studies with randomized, quasi-randomized, and cross-sectional study designs meeting the inclusion criteria were included in this review. USG and landmark-guided DRF manipulations were named cases and controls, respectively. The Newcastle-Ottawa Scale was used to assess the quality of included studies. Results: Thirteen and nine studies were analysed for qualitative and quantitative analysis in this review. Nine hundred fifty-one DRF patients (475 cases and 476 controls) from 9 studies with mean ages of 51.52 ± 11.86 (22-92) and 55.82 ± 11.28 (18-98) years for cases and controls were pooled for this review. The pooled relative risk estimate from the studies included in the meta-analysis was 0.90 (0.74-1.09). There was a 10% decrease in the risk of malalignment with USG than the landmark guided M&R of DRF. The I2 statistic estimated a heterogeneity of 83%. Sensitivity analysis revealed a relative risk of 1.00 (0.96-1.05). Conclusion: The USG-guided manipulation does not prevent malalignment over the landmark-based manipulation of DRF. The risk of bias across the included studies and heterogeneity of 83% mandates further unbiased, high-quality studies to verify the findings of this review.

MRI Features and Treatment for Idiopathic Chondrolysis of the Hip (ICH) in Children: Outcomes of a Systematic Review.

Background: The purpose of this paper was to review the MRI features and treatment for idiopathic chondrolysis of the hip (ICH) in patients aged 18 years or less. Methods: We included studies published in English up to August 2021. We accessed major electronic bibliographic databases on ICH that described MRI features, treatment, or both. We used the Joanna Briggs Institute (JBI) Critical appraisal checklist for case reports for Risk of bias assessment. Results: We pooled 136 hips (125 participants) from 35 studies with 11.6 ± 3.4 years mean age. We had 46, 8, and 106 hips to assess ICH's MRI, pharmacological, and operative interventions. Geometric marrow edema (GME) (P < 0.01), diffuse marrow edema (DME) (P < 0.05), diffuse cartilage loss (DCL) (P < 0.05), and joint effusion (P < 0.05), were significantly associated with time in first MRI reviews. GME (P < 0.01) and focal cartilage loss (FCL) (P < 0.01) decreased significantly between two MRI reviews at median time of 1.75 (IQR 0.93-4.25) and 12.5 (IQR 3.75-19.5) months. Diffuse cartilage loss (P < 0.01) and degenerative changes (P < 0.01) increased significantly between the two MRI reviews. Etanercept, Methotrexate, and Botulinum Neurotoxin A drugs were used by 3, 3, and 1 report to treat ICH. Capsulectomies, total hip arthroplasty, arthrodiastasis, arthrodesis, arthroscopy operations treated 45, 18, 5, 5, and 2 hips. Discussion: GME may be the most specific and early MRI feature in diagnosing ICH. GME and DME show an inverse relationship over time. So, it is with FCL and DCL. Despite reports on the efficacy of biologics, immunomodulators, and operations, early and late ICH management remains controversial due to poor quality studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-022-00684-7.

Corrective derotation osteotomies to treat congenital radioulnar synostosis in children: results of a systematic review and meta-analysis.

Background: The primary objective of this review is to estimate the rotational correction after corrective derotation osteotomies (CDO) for congenital radioulnar synostosis (CRUS). The secondary objective of this review is to identify the complications with CDO in CRUS. Methods: We included studies in the English literature from electronic bibliographic databases Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, Directory of Open access journals (DOAJ), EMBASE, MEDLINE, ProQuest, PubMed, and Scopus up to December 2020 that determined the effects of CDO in CRUS for two or more cases with a mean follow-up of 1 year or more. We used the National Institutes of health quality assessment tool for case series (interventional) and Modified Coleman methodology Score for assessment of risk of bias in the included studies. Results: We pooled 383 forearms (318 participants) from 23 studies with mean age of 6.28 ± 1.75 years. The mean pronation deformity was 72.83 ± 15.64° from 22 studies. The CDO derotated forearm to 10.4 ± 5.90° of mean pronation in 12 studies and 13.47 ± 9.51° of mean supination in nine studies. One study corrected the forearms to a neutral position. The mean derotation from CDO was 73.13 ± 16.54° (35° supination to 130° pronation). The overall mean difference was - 68.26° [95% CI - 86.87, - 49.66] of correction favoring supination. There were eight transient nerve palsies and six compartment syndromes from synostosis site osteotomies (four studies). Discussion: We had poor-quality studies at a high risk of bias on the described tools of assessment. We could estimate the directional effect of CDO in CRUS favoring correction from pronation to supination; however, due to the heterogeneity among studies, we cannot comment on the most efficient and least harmful CDO techniques. The single bone osteotomies seem to be efficient, simple, and reportedly low on complications but need evaluation. We cannot define the indications for correction and expected improvement in functional outcomes from osteotomy techniques. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-021-00582-4.

Do patients with oral squamous cell carcinoma express receptor tyrosine kinase-like orphan receptor 1? Results of an observational study.

CONTEXT: The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a transmembrane protein of the receptor tyrosine kinase family. The expression of ROR1 has been linked to cancers. AIMS: This study aimed to investigate the expression of ROR1 in oral squamous cell carcinoma (OSCC). SETTINGS AND DESIGN: This prospective observational study was conducted at a tertiary referral center for treatment of oral carcinoma from November 2013 to December 2016. SUBJECTS AND METHODS: One-step quantitative reverse transcription-polymerase chain reaction (30 oral cancer tissues and ten normal oral tissue samples) was performed to characterize the expression of the ROR1 gene in oral cancer. STATISTICAL ANALYSIS USED: Analyses of all tumor samples were carried out at least twice, and the mean value was calculated. The differences in ROR1 messenger RNA (mRNA) expression between OSCC tissue and nontumorous gingival tissue was statistically analyzed using Mann-Whitney U-test. The correlations between the clinicopathological parameters and ROR1 mRNA expression were analyzed using Kruskal-Wallis test χ2 value. RESULTS: There were 17, 5, 3 and 1 cases of OSCC of buccal mucosa, tongue and lower alveolus lip, respectively. Nearly 88.5% of cases had a history of tobacco consumption. The most common OSCC type was T2N1M0. There was no difference in ROR1 fold change between controls and cases (P = 0.06), but there was a trend for downregulation of ROR1 expression from controls to cases. Subgroup analysis revealed the downregulation of ROR1 expression in controls versus Grade II that was significant (P = 0.04). CONCLUSIONS: There was no change in the expression of ROR1 between cases and controls. A study involving a larger sample size needs to be formulated and conducted for investigating the relation between expression and regulation of ROR1 in OSCC.

Clinical Outcomes and Global Health After Joint Debridement in Adult-Onset Septic Arthritis: A Prospective Observational Study.

PURPOSE: Despite several reports on risk factors for septic arthritis (SA) in adults, the outcomes on quality of life and joint function are sparsely reported. This study aimed to investigate the quality of life and joint function in adult patients treated for SA. METHODS: This prospective observational study enrolled clinically diagnosed adult SA patients and estimated Euroqol 5-dimension 5 levels (EQ-5D-5L) questionnaire, Euroqol Visual Analog Scale (EQ-VAS) and a validated tool for joint function at 1, 3, 6 and 12 months after debridement. RESULTS: Twenty seven patients (20 males/7 females) with 21 knees, four shoulders, and two elbows were evaluated. The mean age of the cases was 51(± 13.00) years. Three cases sustained mortality. EQ-5D-5L (P < 0.01) and EQ-VAS (P < 0.01) scores improved significantly between all time frames. Mean Knee society (P < 0.01), Shoulder QuickDASH, and Mayo elbow scores improved at all time frames. There was no difference in primary outcomes between early (< 14 days) and late (14 days or more) presentation. There was no difference in primary outcome measures between confirmed and suspected SA. Fifteen patients could ambulate without support, while 6 needed some support for walking at 1 year. CONCLUSION: Improved outcomes can be expected in quality of life and joint function in adults' septic arthritis at the end of 1 year after surgical treatment; however, the effects of delay in presentation need to be investigated further. Isolation of the microorganism from an infected joint has no bearing on the outcome measures.

Clinical and laboratory profile in confirmed vs. suspected septic arthritis patients and its relevance in decision making: A comparative cross-sectional study.

PURPOSE: There were 10%-30% of patients with adult-onset septic arthritis (SA) exhibiting sterile synovial fluid (SF), and the uncertainty in the determining diagnosis of these patients posed a challenge in management. The purpose of this study was to investigate the differences between confirmed (Newman A) and suspected (Newman B & C) SA in adults. METHODS: This was a descriptive study with a cross-sectional study design conducted at a tertiary referral centre from July 2016 to February 2019. Patients aged over 18 years presented to the emergency department with clinical features suggestive of SA and were scheduled to undergo arthrotomy and joint lavage by the treating surgeon were included in the study. Patients with prosthetic joint infections and open joint injuries were excluded. Patients' demographic data, clinical features and laboratory parameters were collected. The clinical and laboratory profile (blood and SF) of the adult patients presenting with features suggestive of SA based on Newman criteria was statistically analyzed by SPSS version 20 software and Microsoft Excel. The categorical variables were expressed as proportions while the continuous variables were expressed as mean (SD) or median (IQR) depending upon the normality of distribution. The difference between the two groups for categorical variables was assessed using the Chi-square test and the difference for continuous variables was assessed using the unpaired t-test and the Mann-Whitney test depending upon normality. A p value < 0.05 was considered significant. RESULTS: Thirty-six patients were divided into confirmed (n = 19) or suspected (n = 17) SA for assessment based on SF culture. The median (IQR) age of the patients was 50 years (37-60 years). There was no significant difference in demographic, clinical and laboratory parameters between the concerned groups. Eight patients presented with fever. Among the confirmed SA cases, 8 were negative for C-reactive protein and 6 had synovial white blood cell count <50,000. Staphylococcus species were isolated in 8 cases. The most common risk factors for SA were chronic kidney disease (25.0%), diabetes mellitus (25.0%), pharmacologic immunosuppression (16.7%), recent joint surgery (11.1%) and distant site infection (11.1%). CONCLUSION: SA is an orthopaedic emergency that needs prompt and aggressive treatment to prevent catastrophic complications. Confirmed and suspected cases of SA exhibit similar demography, clinical features and laboratory parameters at presentation which may mislead the treating surgeon. Management should be based on sound clinical judgment in the event of failure to culture microorganisms.

Plasma d-Dimer Levels in Non-prosthetic Orthopaedic Implant Infection: Can it Aid Diagnosis?

PURPOSE: d-Dimer estimation has been proposed as a reliable biomarker in prosthetic joint infections. Its role in non-prosthetic orthopaedic implant infections has, however, not been studied. The objectives of this study were to assess the levels of plasma d-Dimer in non-prosthetic orthopaedic implant infection. The diagnostic efficiency of d-dimer on orthopaedic implant-related infection was evaluated. METHODS: The study was designed as a cross-sectional comparative study. Patients who presented with orthopaedic implant-related infection as diagnosed by modified MSIS criteria were allocated to case group (n = 49) and patients who underwent surgical procedures with orthopaedic implants with no evidence of infection at 6 weeks postoperatively were allocated to the control group (n = 48). Serum d-Dimer levels were assessed quantitatively using immunoturbidimetric assays in both groups and compared between both groups. RESULTS: The mean (± SD) value of serum d-Dimer in case group was 0.64 (± 0.45) µg/ml and control group was 0.77 (± 0.47) µg/ml. No significant difference was found in serum d-Dimer levels between cases and control groups (p value = 0.183). The diagnostic accuracy of d-dimer in orthopaedic implant-related infection also could not be demonstrated. CONCLUSION: The findings of d-dimer as a marker for the diagnosis of prosthetic joint infections cannot be extrapolated to non-prosthetic orthopaedic implant infection.

Ceftriaxone concentration at the surgical site following systemic and isolated upper limb injection.

BACKGROUND AND AIMS: This study was conducted to find out the equipotent dose of isolated upper limb injection of ceftriaxone in the upper limb (IUL) surgeries under tourniquet that would attain a peak bone marrow concentration (Cmax) similar to systemic (ST) 1 g injection. MATERIAL AND METHODS: Patients were allocated into two groups - ST and IUL. ST group (n = 5) received 1 g of ceftriaxone 20 min before tourniquet inflation, and IUL group received calculated dose (n = 5 in each dosage, i.e., 200, 100, 75, and 50 mg) diluted in 50 mL of normal saline distally after tourniquet inflation. Venous and bone marrow samples were collected at various time intervals intra- and post-operatively. Ceftriaxone concentration was analyzed by high-performance liquid chromatography. RESULTS: There was no significant difference between Cmax following ST 1 g injection and IUL injection with 75 mg (155.8 ± 2.1 vs 158.5 ± 3.1 µg/mL, respectively; P = 0.1). There was significant difference in area under curve (AUC) and t½ between ST 1 g injection and IUL injection with 75 mg of ceftriaxone (AUC 1285 ± 67 vs 784.4 ± 28 µg/mL/h, respectively; P < 0.001), (t½ 5.2 ± 0.5 vs 4.7 ± 0.3 h, respectively; P < 0.001). None of the patients in the ST and IUL groups had post-operative infection up to a period of 1 week duration. CONCLUSION: IUL injection with 75 mg of ceftriaxone can be equipotent and as effective as ST 1 g injection in upper limb orthopedic surgeries under tourniquet.

Does operative fixation of isolated fractures of ulna shaft results in different outcomes than non-operative management by long arm cast?

OBJECTIVE: The optimal treatment for isolated fractures of ulnar shaft is debatable. The purpose of this study was to compare functional outcomes and radiological union in patients treated for isolated fractures of the ulnar shaft by open reduction and internal fixation and a long arm cast. METHODS: This prospective study was conducted at level I trauma center from November 2014 to March 2016. 30 patients with isolated fractures of ulnar shaft were randomized to two groups to receive treatment by open reduction and internal fixation by plates and screws and a long arm cast. Outcome assessment was done by Disabilities of Arm Shoulder and Hand (DASH) score, range of motion at wrist and elbow, grip strength and radiological union. Quantitative variables were summarized Mean or Median. Normality was assessed using Kolmogorov-Smirnov test. Independent samples t-test and Mann-Whitney test were used for normally distributed variables and non-normally distributed variables respectively. Categorical variables were summarized as proportions. Effect of the intervention for categorical variables was assessed using Chi-square test. RESULTS: There was no difference between the groups for pain on Visual Analogue Scale (VAS), grip strength, DASH score, and union at the end of 12 months. There was no difference between the groups for range of motion at the elbow and wrist. 12 (85.7%) patients in the ORIF group and 15 (93.7%) in the cast group united at the end of 12 months. The mean time to union was 13 weeks in the ORIF group and 18 weeks in the cast group. CONCLUSION: Open reduction and internal fixation results in anatomical restoration of ulna, but this does not translates to better functional outcomes in short term (12 months).

Does age, time since injury and meniscal injury affect short term functional outcomes in arthroscopic single bundle anterior cruciate ligament reconstruction?

PURPOSE: We conducted this study to correlate the short term clinical outcomes after anterior cruciate ligament (ACL) reconstruction with patients' age, time since injury and associated meniscal injury. METHODS: A total of 43 patients who underwent ACL reconstruction between October 2013 and February 2015 were taken for the study. Preoperative demographic data, clinical scores (Lysholm, IKDC) were recorded for each patient. Time since injury and associated meniscal injuries were recorded. Then a standardized surgical technique was used for each graft type. They were followed up for 6 months and the Lysholm and IKDC scores were evaluated. RESULTS: Only 33 patients completed 6 months follow-up at the end of this study. Twenty-four patients (72.7%) were in the age group of 18-30 years. Nine patients belonged to age group 30-50 years (27.3%). The p value for differences in Lysholm scores between the two age groups was not significant (0.339). The p value for differences in IKDC scores between the two age groups was not significant either (0.138). The mean Lysholm scores were 93.86 ± 3.024 for the group who presented <6 months post-injury, 92 ± 5.494 for the group who presented between 6 months and 1 year and 94.64 ± 3.104 for the group who presented after 1 year; whereas the mean IKDC scores were 92.43 ± 0.793, 90.64 ± 6.598 and 90.89 ± 2.113 respectively. The correlation of outcomes with meniscal injury had no statistical significance. CONCLUSION: Based on our study, we conclude that age, time since injury and associated meniscal injury does not affect short term functional outcome in ACL reconstruction.

Probing the Conformation of an IgG1 Monoclonal Antibody in Lyophilized Solids Using Solid-State Hydrogen-Deuterium Exchange with Mass Spectrometric Analysis (ssHDX-MS).

Therapeutic proteins are often formulated as lyophilized products to improve their stability and prolong shelf life. The stability of proteins in the solid-state has been correlated with preservation of native higher order structure and/or molecular mobility in the solid matrix, with varying success. In the studies reported here, we used solid-state hydrogen-deuterium exchange with mass spectrometric analysis (ssHDX-MS) to study the conformation of an IgG1 monoclonal antibody (mAb) in lyophilized solids and related the extent of ssHDX to aggregation during storage in the solid phase. The results demonstrate that the extent of ssHDX correlated better with aggregation rate during storage than did solid-state Fourier-transform infrared (ssFTIR) spectroscopic measurements. Interestingly, adding histidine to sucrose at different formulation pH conditions decreased aggregation of the mAb, an effect that did not correlate with structural or conformational changes as measured by ssFTIR or ssHDX-MS. Moreover, peptide-level ssHDX-MS analysis in four selected formulations demonstrated global changes across the structure of the mAb when lyophilized with sucrose, trehalose, or mannitol, whereas site-specific changes were observed when lyophilized with histidine as the sole excipient.

Effects of Drying Process on an IgG1 Monoclonal Antibody Using Solid-State Hydrogen Deuterium Exchange with Mass Spectrometric Analysis (ssHDX-MS).

PURPOSE: Lyophilization and spray drying are widely used to manufacture solid forms of therapeutic proteins. Lyophilization is used to stabilize proteins vulnerable to degradation in solution, whereas spray drying is mainly used to prepare inhalation powders or as an alternative to freezing for storing bulk drug substance. Both processes impose stresses that may adversely affect protein structure, stability and bioactivity. Here, we compared lyophilization with and without controlled ice nucleation, and spray drying for their effects on the solid-state conformation and matrix interactions of a model IgG1 monoclonal antibody (mAb). METHODS: Solid-state conformation and matrix interactions of the mAb were probed using solid-state hydrogen-deuterium exchange with mass spectrometric analysis (ssHDX-MS), and solid-state Fourier transform infrared (ssFTIR) and solid-state fluorescence spectroscopies. RESULTS: mAb conformation and/or matrix interactions were most perturbed in mannitol-containing samples and the distribution of states was more heterogeneous in sucrose and trehalose samples that were spray dried. CONCLUSIONS: The findings demonstrate the sensitivity of ssHDX-MS to changes weakly indicated by spectroscopic methods, and support the broader use of ssHDX-MS to probe formulation and process effects on proteins in solid samples.

Radiologic assessment of femoral and tibial tunnel placement based on anatomic landmarks in arthroscopic single bundle anterior cruciate ligament reconstruction.

BACKGROUND: Accurate tibial and femoral tunnel placement has a significant effect on outcomes after anterior cruciate ligament reconstruction (ACLR). Postoperative radiographs provide a reliable and valid way for the assessment of anatomical tunnel placement after ACLR. The aim of this study was to examine the radiographic location of tibial and femoral tunnels in patients who underwent arthroscopic ACLR using anatomic landmarks. Patients who underwent arthroscopic ACLR from January 2014 to March 2016 were included in this retrospective cohort study. MATERIALS AND METHODS: 45 patients who underwent arthroscopic ACLR, postoperative radiographs were studied. Femoral and tibial tunnel positions on sagittal and coronal radiographic views, graft impingement, and femoral roof angle were measured. Radiological parameters were summarized as mean ± standard deviation and proportions as applicable. Interobserver agreement was measured using intraclass correlation coefficient. RESULTS: The position of the tibial tunnel was found to be at an average of 35.1% ± 7.4% posterior from the anterior edge of the tibia. The femoral tunnel was found at an average of 30% ± 1% anterior to the posterior femoral cortex along the Blumensaat's line. Radiographic impingement was found in 34% of the patients. The roof angle averaged 34.3° ± 4.3°. The position of the tibial tunnel was found at an average of 44.16% ± 3.98% from the medial edge of the tibial plateau. The coronal tibial tunnel angle averaged 67.5° ± 8.9°. The coronal angle of the femoral tunnel averaged 41.9° ± 8.5°. CONCLUSIONS: The femoral and tibial tunnel placements correlated well with anatomic landmarks except for radiographic impingement which was present in 34% of the patients.

Correlation of tunnel widening and tunnel positioning with short-term functional outcomes in single-bundle anterior cruciate ligament reconstruction using patellar tendon versus hamstring graft: a prospective study.

OBJECTIVE: To study the correlation between tunnel widening and tunnel position with short-term functional outcomes post-ACL reconstruction with patellar tendon and hamstring autografts in young adults. MATERIALS AND METHODS: A total of 33 patients who underwent ACL reconstruction between October 2013 and February 2015 were included and followed up for 6 months. A standardized surgical technique was used for each graft type. Intra-op arthroscopy findings and drilled tunnel diameters were noted. They were followed up for 3 and 6 months. Radiological assessment was done at 3 and 6 months with clinical score assessment at 6 months. RESULTS: At 6 months, clinical scores were comparable in both groups. Tunnel widening in both femoral and tibial tunnel at 3 and 6 months were significantly higher in STG group (p values <0.05). The rate of widening was higher in 0-3 months and reduced in 3-6 months. There was statistically significant negative correlation between femoral tunnel widening by CT and IKDC score at 6 months (p value 0.049). We found a positive correlation between posterior positioning of femoral tunnel and Lysholm and IKDC scores. The correlation with Lysholm scores was statistically significant (p value 0.046). CONCLUSION: To conclude, tunnel widening is more with hamstrings graft. Femoral tunnel widening has significant negative correlation with that of IKDC scores at 6 months. Posterior femoral tunnel positioning and Lysholm scores at 6 months had significant correlation.

Critical considerations for developing nucleic acid macromolecule based drug products.

Protein expression therapy using nucleic acid macromolecules (NAMs) as a new paradigm in medicine has recently gained immense therapeutic potential. With the advancement of nonviral delivery it has been possible to target NAMs against cancer, immunodeficiency and infectious diseases. Owing to the complex and fragile structure of NAMs, however, development of a suitable, stable formulation for a reasonable product shelf-life and efficacious delivery is indeed challenging to achieve. This review provides a synopsis of challenges in the formulation and stability of DNA/m-RNA based medicines and probable mitigation strategies including a brief summary of delivery options to the target cells. Nucleic acid based drugs at various stages of ongoing clinical trials are compiled.