Diagnostic exome identifies a novel PRKG2 mutation in a proband with skeletal dysplasia.

This graphic abstract combines pedigree, dysmorphology features, radiographs, and the PRKG2 protein domain, specifically the CNB-A regulatory domain, which harbors a mutation resulting in premature protein termination.

Mobilization under anaesthesia for correction of knee flexion deformity in haemophilia.

INTRODUCTION: Haemophilia patients not treated with primary or secondary prophylaxis, often present with recurrent haemarthrosis. Knee is the most frequently involved joint leading to disabling knee flexion deformity (KFD). Here, we present a retrospective study of our experience on the role of mobilization under general anaesthesia in the correction of KFD. AIM: To study the effectiveness of mobilization under anaesthesia (MUA) for correction of knee flexion deformity (KFD) in persons with haemophilia (PWH). METHODS: Outcome of all patients managed with MUA in our multidisciplinary haemophilia clinic from 2008 to 2019 were included for analysis. PWH with KFD > 20 degree who underwent MUA were included in the study. Under general anaesthesia and cover of clotting factor replacement, gentle joint mobilization was done to achieve maximal correction in flexion deformity, followed by above knee casting in this position. The outcome measures assessed were reduction in knee flexion deformity following MUA and complications, if any. RESULTS: Thirty patients (34 knees) with knee flexion deformity were included in the study. Mean age of the study population was 14.23 years ± 8.3. Study population was analysed in two groups, Group 1 included patients who underwent single MUA and Group 2, patients who underwent two or more MUA. There was significant improvement in KFD correction in both groups. [Group 1; Mean difference: 22 ± 13.7, p value -0.01, 95% CI (16.4-27.5) and Group 2; Mean difference 48.8 ± 19.8, p value -0.00, 95% CI (34.2-64.5)]. CONCLUSION: MUA can be effective in the short-term correction of KFD in PWH particularly those below 15 years of age. It should be done judiciously when target correction is not achieved with other physical methods.

Osteogenesis imperfecta: Novel genetic variants and clinical observations from a clinical exome study of 54 Indian patients.

Osteogenesis imperfecta (OI) is a group of inherited disorders with increased bone fragility and wide genetic heterogeneity. We report the outcome of clinical exome sequencing validated by Sanger sequencing in clinically diagnosed 54 OI patients in Indian population. In 52 patients, we report 20 new variants involving both dominant and recessive OI-specific genes and correlate these with phenotypes. COL1A1 and COL1A2 gene variants were identified in 44.23%, of which 28.84% were glycine substitution abnormalities. Two novel compound heterozygous variants in the FKBP10 gene were seen in two unrelated probands. A novel heterogeneous duplication of chromosomal region chr17: 48268168-48278884 from exons 1-33 of the COL1A1 gene was found in one proband. In five probands, there were additional variants in association with OI. These were ANO5 in association with CRTAP in two probands of the same family causing gnathodiaphyseal dysplasia, COL5A2 with LEPRE1 causing Ehlers Danlos syndrome, COL11A1 in addition to COL1A1 causing Stickler syndrome, and a previously unreported combination of SLC34A1 gene variant with FKBP10 leading to Fanconi renal tubular syndrome type II. Our findings demonstrate the efficacy of clinical exome sequencing in screening OI patients, classifying its subtypes, and identifying associated disorders in consanguineous populations.

Ultrasound and magnetic resonance imaging for the detection of blood: An ex-vivo study.

OBJECTIVES: Early detection of bleeding into a joint is crucial in patients with haemophilia. This study was designed to evaluate the sensitivity of ultrasonography (USG) and magnetic resonance imaging (MRI) to detect the presence of blood in small concentrations in a simulated model to mimic joint bleeding. MATERIALS AND METHODS: Different concentrations of blood in plasma, varying from 0.1% to 45%, were collected in 10-ml plastic syringes and imaged using 12 and 18 MHz USG transducers and with 1.5T and 3T MRI scanners, at different intervals of time following dilution. The images were scored for the presence of blood by four experienced radiologists who were blinded to the concentration of blood. RESULTS: Within the first 2 h, the 18 MHz transducer was able to detect blood consistently up to 0.5%, whereas the 12 MHz transducer could consistently identify blood up to 1.4%. After the first 12 h, both transducers were able to detect blood up to 0.5% concentration. However, at concentrations below 0.5%, there was discordance in the ability to detect blood, with both transducers. There was no correlation between the signal intensities of MRI images and concentration of blood, at different time intervals, irrespective of the magnetic field strength. CONCLUSIONS: Detection of blood using the USG is dependent on variables such as the concentration of blood, frequency of the transducer used and timing of the imaging. As the concentration of blood decreases below 0.5%, the discordance between the observers increases, implying that the detection limit of USG affects its reliability at lower concentrations of blood. Caution is urged while interpreting USG imaging studies for the detection of blood in symptomatic joints.

A rare presentation of primary lymphoma of bone with aneurysmal bone cyst-like changes.

Primary lymphoma of bone occurs rarely in children with variable imaging findings ranging from a lytic lesion to an aggressive permeative lesion. We detail a case report with review of literature of a 14-year-old boy with a rare presentation of primary lymphoma of bone with aneurysmal bone cyst-like changes. The lesion was surgically excised as management for aneurysmal bone cyst but histopathological examination of the excised tissue revealed a non-Hodgkin's type of lymphoma. This unique type of aneurysmal bone cyst-like presentation has not been well characterised until now in the imaging spectrum of primary lymphoma of bone. Clinicians need to be aware of this uncommon presentation for early intervention and appropriate management of this malignancy in children.

Perthes-Like Disorder in a Child with Atypical Bohring-Opitz Syndrome.

CASE: Bohring-Opitz syndrome is characterized by facial dysmorphism, intellectual disability, specific upper-limb posturing, and developmental delay. We report a case of 14-year-old girl with bilateral hip pain and loss of mobility. Clinical exome sequencing showed a proband with a heterozygous pathogenic nonsense variant in ASXL1 gene. CONCLUSION: The Perthes-like clinical and radiological features in the hip and the absence of classical upper-limb features are a new phenotype and hence presented here.

Decreased femur tunnel widening after augmented suspensory fixation compared to suspensory fixation for single bundle hamstring ACL reconstruction.

Background: Tunnel widening after Anterior cruciate ligament (ACL) reconstruction using a hamstring graft is known to occur at follow-up. Our study aimed to investigate the effect of suspensory fixation augmentation using an interference screw on tunnel widening in single-bundle hamstring ACL reconstruction. Methods: 48 patients who had single bundle ACL reconstruction with femoral fixed loop fixation technique in 15 knees, and, fixed loop with augmented aperture (bio screw) fixation in 33 knees were analyzed. The width of the tunnel was measured using radiographs immediate post-op and at follow-up within 1 year. Computerized Tomogram (CT) measurements of the tunnels and functional scores were also done with overall follow-up for the fixed loop group being 21.33 months (Standard Deviation (SD)11.14) and the Augmentation group 9.12 months (SD 3.83). Results: Midpoint femur tunnel widening was reduced in the augmentation group, with measurements of 0.74 (SD 1.05) mm Antero Posterior (AP) and 1.01 (SD 1.04) mm in the Lateral view, compared to 1.54 (SD 1.48) mm AP and 1.79 (SD1.47 mm) in the Lateral for the fixed button group. The radiological widening was considerably less in the augmentation group with a p-value of 0.07. AP aperture widening in the augmentation group was 1.25(SD 1.10 mm), and 1.09(SD0.98) mm in the lateral view. The fixed button-only group measured 1.53 (SD1.30) mm in the AP, and 1.65 (SD 1.29) mm in the lateral view, both of which were not statistically significant. The follow-up Lysholm and International Knee Documentation Committee (IKDC) scores were similar for the 2 groups. Conclusion: Femoral tunnel midpoint and aperture widening were reduced with the fixed loop with aperture (bio screw) augmentation technique for hamstring grafts in single bundle ACL fixation within 1 year with comparable functional scores. Level of evidence: 4.

MRI predictors of infectious etiology in patients with unilateral sacroiliitis.

BACKGROUND: Unilateral presentation of sacroiliitis is a diagnostic dilemma, especially between infection and inflammatory sacroiliitis associated with spondyloarthritis, requiring an early and accurate diagnosis. OBJECTIVE: To assess the utility of magnetic resonance imaging (MRI) in differentiating infective versus inflammatory etiology in unilateral sacroiliitis. MATERIALS AND METHODS: Retrospective review of the MRI of 90 patients with unilateral sacroiliitis, having an established final diagnosis. MR images were evaluated for various bone and soft tissue changes using predefined criteria and analyzed using univariate and multivariate regression analysis. RESULTS: Among the 90 patients, infective etiology was diagnosed in 66 (73.3%) and inflammatory etiology in 24 (26.7%). Large erosions, both iliac and sacral-sided edema, joint space involvement with effusion or synovitis, soft tissue edema, elevated ESR/CRP, and absence of capsulitis and enthesitis were associated with infection (p < .001). The independently differentiating variables favoring infection on multivariate analysis were-both iliac and sacral-sided edema (OR 4.79, 95% CI: 0.96-23.81, p = .05), large erosions (OR 17.96, 95% CI: 2.66-121.02, p = .003), and joint space involvement (OR 9.9, 95% CI: 1.36-72.06, p = .02). Exclusive features of infection were osteomyelitis, sequestra, abscesses, sinus tracts, large erosions, and multifocality. All infective cases had soft tissue edema, joint space involvement, elevated ESR, and no capsulitis. CONCLUSION: MRI evaluation for the presence and pattern of bone and joint space involvement, soft tissue involvement, and careful attention to certain exclusive features will aid in differentiating infectious sacroiliitis from inflammatory sacroiliitis.

Teleradiology and technology innovations in radiology: status in India and its role in increasing access to primary health care.

Background: There is an inequitable distribution of radiology facilities in India. This scoping review aimed at mapping the available technology instruments to improve access to imaging at primary health care; to identify the facilitators and barriers, and the knowledge gaps for widespread adaptation of technology solutions. Methods: A search was conducted using broad inclusive terms non-specific to subtypes of medical imaging devices or informatics. Work published in the English language between 2005 and 2022, conducted primarily in India, and with full manuscripts were included. Two authors independently screened the abstracts against the inclusion criteria for full-text review and a senior author settled discrepancies. Data were extracted using DistillerSR software. Findings: 43 original articles and 52 non-academic materials were finally reviewed. The data was from 10 Indian states with n = 9 from rural settings. The broad trends in original articles were: connectivity using teleradiology (n = 7), mobile digital imaging units (n = 9), artificial intelligence (n = 16); mobile devices and smartphone applications (n = 7); data security (n = 7) and web-based technology (n = 2); public-private partnership (n = 9); cost (n = 2); concordance (n = 19); evaluation (n = 4); implementation (n = 2). Interpretation: Available evidence suggests that teleradiology when combined with AI and mobile digital imaging units can address radiologist shortages; strengthen programs aimed at population screening and emergency care. However, there is insufficient data on the scale of teleradiology networks within India; needs assessment; cost; facilitators, and barriers for implementation of technologies solutions in primary healthcare settings. Regulations governing quality standards, data protection, and confidentiality are unclear. Funding: The authors are The Lancet Citizen's Commission fellows. The Lancet Commission has received financial support from the Lakshmi Mittal and Family South Asia Institute, Harvard University; Christian Medical College, Vellore (CMC), Vellore; Azim Premji Foundation, Infosys; Kirloskar Systems Ltd.; Mahindra & Mahindra Ltd.; Rohini Nilekani Philanthropies; and Serum Institute of India. The views expressed are those of the author(s) and not necessarily those of the Lancet Citizens' Commission or its partners.

"De Novo" Hypercapnic Respiratory Failure Unmasking Neuromuscular Disorders: Experiences From a Tertiary Care Center and Review of Literature.

OBJECTIVES: Neuromuscular disorders could have respiratory involvement early or late into illness. Rarely, patients may present with a hypercapnic respiratory failure (with minimal motor signs) unmasking an underlying disease. There are hardly any studies which have addressed the spectrum and challenges involved in management of this subset, especially in the real-world scenario. METHODS: A retrospective study comprising consecutive patients hospitalized with hypercapnic respiratory failure as the sole/dominant manifestation. The clinical-electrophysiological spectrum, phrenic conductions, diaphragm thickness, and outcomes were analyzed. RESULTS: Twenty-seven patients were included, the mean age was 47.29 (SD 15.22) years, and the median duration of respiratory symptoms was 2 months (interquartile range [IQR] 1-4). Orthopnea was present in 23 patients (85.2%) and encephalopathy in 8 patients (29.6%). Phrenic nerve latencies and amplitudes were abnormal in 83.3% and 95.6%, respectively. Abnormal diaphragm thickness was noted in 78.5%. Based on a comprehensive electrophysiological strategy and paraclinical tests, an etiology was established in all. Reversible etiologies were identified in 17 patients (62.9%). These included myasthenia gravis (anti-AChR and MuSK), inflammatory myopathy, riboflavin transporter deficiency neuronopathy, Pompe disease, bilateral phrenic neuritis, and thyrotoxicosis. Respiratory onset motor neuron disease was diagnosed in 8 patients (29.6%). Despite diaphragmatic involvement, a functional respiratory recovery was noted at discharge (45%) and last follow-up (60%). Predictors for good outcomes included female sex, normal nerve conductions, and recent-onset respiratory symptoms. DISCUSSION: A good functional recovery was noted in most of the patients including respiratory onset motor neuron disease. A systematic algorithmic approach helps in proper triaging, early diagnosis, and treatment. Clinical and electrodiagnostic challenges and observations from a tertiary care referral center are discussed.

SERPINF1 gene variants causing late-onset progressive deforming osteogenesis imperfecta - A study of 18 patients from India.

SERPINF1 gene variants lead to a severe type of osteogenesis imperfecta (OI) attributed to defects in the matrix mineralization. We present 18 patients with SERPINF1 gene variants leading to severe progressive deforming OI, the largest series in the world to date. These patients were normal at birth and had the first fracture between 2 months to 9 years; progression of deformities was seen in 12 adolescents who became nonambulatory. Radiologically, compression fractures with kyphoscoliosis, protrusio acetabuli, and lytic lesions in the metaphysis and pelvis were seen in older children with classical popcorn appearance in the distal femoral metaphysis in three. By exome sequencing and targeted sequencing, we identified ten variants. One was unreported and novel; three other novel variants in this series were reported earlier. The recurrent deletion inframe mutation p.phe277del was found in 5 patients from three families. Alkaline phosphatase was elevated in all children on the first visit. Bone mineral density was low in all patients and showed improvement at two years in seven children on regular pamidronate therapy. For others, the 2 year BMD data were not available. The Z scores for four of the seven children showed worsening at the 2-year follow-up.

Computed Tomography-Guided Spinal Biopsy in Suspected Infective Spondylodiscitis: An Institutional Review of Its Utility.

Background Infectious spondylodiscitis is a debilitating condition and evidence-based medicine dictates confirming the diagnosis before treatment. Computed tomography-guided spinal biopsy plays a major role and hence we would like to determine its utility in current clinical practice. Purpose The purpose of this study is to determine the percentage of confirmatory positives of CT-guided spinal biopsy in patients who were clinicoradiologically diagnosed with infectious spondylitis. Material and Methods A retrospective analysis of patients who underwent CT-guided biopsy for suspected infectious spondylodiscitis from 2017 to 2021 in a tertiary medical center was done. The data were filtered and obtained from the electronic database of the institution. Results In all, 259 patients underwent CT-guided biopsy of the spine. The procedure provided confirmatory results in 149 (57.5%) biospecimens. Histopathology examination was confirmatory in 95 (36.6%) of the 241 biospecimens sent. The Mycobacteria Growth Indicator Tube (MGIT) was confirmatory in 51 (19.9%) of the 250 biospecimens sent and drug resistance was seen in 6/51 (11.7%) biospecimens. Xpert TB provided confirmatory results in 72 (27.8%) of the 254 biospecimens sent and rifampicin resistance was seen in 16/72 (22.2%) biospecimens. Bacterial culture was confirmatory in 29 (11.2%) of the 250 biospecimens sent. The complication documented in this study was 0.3%. Conclusion CT-guided spinal biopsy for suspected vertebral osteomyelitis is a safe and effective minimally invasive procedure. It demonstrates a positive yield in more than half of the patients. Knowing the outcome, the patients can be appropriately counseled prior to the procedure. CT-guided biopsy results were affected by prior administration of ATT (antitubercular therapy) in suspected tuberculous spondylitis patients.

Spinopelvic Mobility Pattern and Acetabular Anteversion in Stiff Hips With Ankylosing Spondylitis After Total Hip Arthroplasty.

Background: Fused hips with spine stiffness in ankylosing spondylitis (AS) reduce spinopelvic mobility. We aimed to assess spinopelvic mobility pattern and acetabular anteversion in AS after total hip arthroplasty (THA). Material and methods: Ninety-four stiff hips in 58 AS individuals (mean age: 37.05) who underwent THA between 2012 and 2018 with a modified lateral approach were included. Twenty-three hips were fused, and 71 hips had mean flexion of 37.67°. Pelvic tilt, pelvic inclination, sacral slope (SS), and lumbar lordosis were correlated with THA, and functional outcomes were assessed at 34.6-month mean follow-up. Results: Thirty-seven had a stuck sitting pattern with stuck standing seen in 4 individuals. SS standing before and after THA were 25.08° and 27.30°. SS sitting was 8.99° compared to 16.80°. SS from sitting to standing was reduced (17.7°) in 17 individuals. Spine stiffness in extension was seen in 4 out of 37. Mean acetabular inclination after THA was 42.67°, and acetabular anteversion was 17.48°. Flexion after THA improved to mean 98.47°. Changes in SS from sitting to standing were correlated with THA (r-value: 0.93, P-value: .0001). The Harris Hip Score improved from 25.31 to 82.39 (P-value <.05), and the mean 12-item Short Form Survey at review was 52.18 and 59.55 (physical and mental components). The mean Western Ontario and Mc Master Universities Arthritis Index score was 17.56. Conclusions: Spinopelvic mobility change was <10° after THA in AS, stuck sitting was seen in 37 of 58 (63.8%), and stuck standing was seen in 4 of 58 (6.9%), including spine stiffness in flexion or extension. Acetabular anteversion assessed was 17.48° (standard deviation: 4.41), with significant functional improvement. Level of Evidence: Level 4.

Prevalence of the additional head of quadriceps femoris in the South Indian population: a cadaveric and radiological study.

Quadriceps femoris is an extensor muscle in the anterior compartment of thigh and is traditionally taught to be composed of four heads. Recently, there is an increased interest in the occurrence of an additional muscle head of quadriceps femoris. But scientific knowledge regarding its incidence is lacking in the South Indian population. This study was done to confirm the presence of the additional head by routine anatomic dissection and radiological imaging techniques. Forty-one formalin fixed human cadaveric lower limbs were dissected and the morphology of the additional head was noted. Retrospective analysis of 88 MRI images of patients was done. The additional muscle head was present in 43.9% of the cadaveric lower limbs and was consistently located between the vastus lateralis and vastus intermedius. It originated from variable portions of the greater trochanter, intertrochanteric line, lateral lip of linea aspera and lateral surface of the shaft of femur and inserted either as a muscle belly or as an aponeurosis into the vastus intermedius (55.6%), vastus lateralis (22.2%) or directly into the base of the patella. It received its vascular supply from branches of the lateral circumflex femoral artery and was innervated by branches from the posterior division of the femoral nerve. In addition, the additional muscle head was identified by MRI and its incidence was reported to be 30.68% for the first time in living subjects. The result of this study provides additional information in understanding the morphology of the quadriceps femoris muscle.

Role of Ultrasound Acoustic Radiation Force Impulse in Differentiating Benign from Malignant Superficial Lymph Nodes.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of acoustic radiation force impulse (ARFI) imaging in differentiating benign from malignant peripheral lymphadenopathy. MATERIALS AND METHODS: This was a prospective study approved by the Institutional Review Board with financial grant for the same. Ultrasound and ARFI imaging of peripheral lymph nodes were performed and correlated with pathological results, which were used as the reference standard. The virtual touch tissue imaging and virtual touch tissue quantification parameters of ARFI were analyzed in 86 lymph nodes, of which 78 were included in the study. Using receiver operating characteristic curve analysis, the diagnostic usefulness of ARFI values were evaluated with respect to their sensitivity, specificity, and area under the curve. RESULTS: The mean area ratio of benign lymph nodes was 0.88 (±0.2) and that of malignant lymph nodes was 1.17 (±0.14). The mean shear wave velocities (SWV) of benign and malignant lymph nodes were 2.02 m/s (±0.94) and 3.7 m/s (±2.27), respectively. The sensitivity and specificity of virtual touch imaging area ratio in differentiating benign from malignant lymph nodes was 97% and 77%, of SWV was 71% and 70%, and of SWV ratio was 68% and 79%, respectively. CONCLUSION: As ARFI was found to have a superior diagnostic performance over conventional ultrasound and color Doppler in the characterization of lymph nodes, we recommend its routine use in differentiating benign from malignant nodes.

Subtrochanteric femoral shortening for hip centre restoration in complex total hip arthroplasty with functional outcome.

AIMS: Complex total hip arthroplasty (THA) with subtrochanteric shortening osteotomy is necessary in conditions other than developmental dysplasia of the hip (DDH) and septic arthritis sequelae with significant proximal femur migration. Our aim was to evaluate the hip centre restoration with THAs in these hips. METHODS: In all, 27 THAs in 25 patients requiring THA with femoral shortening between 2012 and 2019 were assessed. Bilateral shortening was required in two patients. Subtrochanteric shortening was required in 14 out of 27 hips (51.9%) with aetiology other than DDH or septic arthritis. Vertical centre of rotation (VCOR), horizontal centre of rotation, offset, and functional outcome was calculated. The mean followup was 24.4 months (5 to 92 months). RESULTS: The mean VCOR was 17.43 mm (9.5 to 27 mm) and horizontal centre of rotation (HCOR) was 24.79 mm (17.2 to 37.6 mm). Dislocation at three months following acetabulum reconstruction required femoral shortening for offset correction and hip centre restoration in one hip. Mean horizontal offset was 39.72 (32.7 to 48.2 mm) compared to 42.89 (26.7 to 50.6 mm) on the normal side. Mean Harris Hip Score (HHS) of 22.64 (14 to 35) improved to 79.43 (68 to 92). Mean pre-operative shortening was 3.95 cm (2 to 8 cm). Residual limb length discrepancy was 1.5 cm (0 to 2 cm). Sciatic neuropraxia in two patients recovered by six months, and femoral neuropraxia in one hip recovered by 12 months. Mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was 13.92 (9 to 19). Mean 12-item short form survey (SF-12) physical scores of 50.6 and mental of 60.12 were obtained. CONCLUSION: THA with subtrochanteric shortening is valuable in complex hips with high dislocation. The restoration of the hip centre of rotation and offset is important in these hips. LEVEL OF EVIDENCE IV: Femoral shortening useful in conditions other than DDH and septic sequelae.Restoration of hip centre combined with offset to be planned and ensured.

Utility of CT imaging in differentiating sacroiliitis associated with spondyloarthritis from gouty sacroiliitis: a retrospective study.

Sacroiliitis is one of the criteria for classification as spondyloarthritis (SpA), though not unique to SpA. Other conditions including gout may be erroneously diagnosed as SpA due to sacroiliitis. The objective was to identify specific CT findings in sacroiliitis associated with SpA and gout. In this retrospective study, CT images of patients with sacroiliitis and clinical diagnosis of gout or SpA from 2010 to 2015 were independently reviewed by two radiologists, blinded to diagnosis. Axial and coronal oblique images were analyzed for characteristics of erosions. The receiver operator characteristic curve was constructed to analyze the discriminating ability of radiological findings. CT SI joint images of 11 patients with gout and 224 patients with SpA were re-analyzed. There was excellent agreement between the radiologists (ICC from 0.78 to 1). Erosions were more numerous in SpA. Erosions in gout were associated with tophi in 65.7% (73/111). Erosions in gout were para-articular and had sclerotic margins, overhanging edges, and multilobulated base (P < 0.0001 for all). Length and depth of erosions were more in gout as compared to SpA. AUCs for length, depth of erosions, and subchondral sclerosis were 0.665, 0.694, and 0.991, respectively. Subchondral sclerosis ≤ 4.5 mm had a sensitivity and specificity of 100 and 96%, respectively, for diagnosis of gout. In addition to known radiological features of gout, multilobulated base of erosions and absence of subchondral sclerosis could possibly distinguish sacroiliitis in SpA from gout. Our limited analysis suggests that CT imaging could help in differentiating the two.