Factors influencing correction rate following hemiepiphysiodesis using tension band plates for deformities around the knee: a multivariate analysis study.

PURPOSE: The aim of this study was to appraise various factors influencing the correction rate in temporary hemiepiphysiodesis (THE) around the knee joint. Specifically, the study analysed the relationship of correction rate with age, gender, aetiology, type and location of deformity. METHODS: The retrospective study included children who underwent THE for a coronal plane deformity (genu valgus or varum) around the knee joint (distal femur or proximal tibia) over a ten year period (2010-2020). The primary outcome of interest was the correction rate of the deformity. RESULTS: Thirty-three children (27 females and 6 males) with a mean age of 8.1 years involving 86 plates were included in the study. The mean correction achieved was 12.2° over a treatment period of 13.3 months. Subgroup analysis showed significant differences between the type (varus (0.8° per month), valgus (1.1° per month)) and the location of deformity femur (1.2° per month) and tibia (0.7° per month)]. On multivariate analysis, the location and the duration of treatment showed significant associations with the correction rate. CONCLUSION: The correction of coronal deformities following temporary hemiepiphysiodesis is influenced by several factors. Valgus, femoral and deformities in younger children correct at a faster rate. Location of deformity and duration of treatment emerged as potential factors affecting the correction rate.

Effect of non-vascularized fibular harvest on the donor limb: radiological evaluation at a mean follow-up of twelve point eight years.

PURPOSE: The study is aimed at evaluating the long-term (at a minimum follow-up of 10 years) impact of non-vascularized fibular harvest on the donor limbs. METHODS: There were 27 donor limbs (n = 19 children) available for retrospective radiological review. The graft was obtained bilaterally in eight patients. The following parameters were evaluated in the follow-up radiographs: continuity/non-continuity of fibular regenerate, width of the regenerated fibula, distal fibular station, medial proximal tibial angle, posterior proximal tibial angle, lateral distal tibial angle (LDTA), anterior distal tibial angle, and tibia diaphyseal angulation (interphyseal angles). For analysis and comparisons, the donor limbs were compared to the healthy limbs (controls) of the children with unilateral harvest. Additionally, the impact of continuous and non-continuous fibular regeneration was separately analyzed. RESULTS: The mean child's age at the time of fibular harvest was four years. The mean follow-up was 12.8 years. The fibula was found regenerated in continuity in 22 limbs of 15 children (81.5%). When analyzed as a combined group (both continuous and non-continuous fibular regenerations), all the donor limb radiological parameters matched those of healthy limbs except LDTA (p = 0.04). In the subgroup analysis between non-continuous and continuous fibulae, significant abnormalities were again obvious in LDTA (p = 0.0001). The non-continuous fibulae were significantly lesser in width. All limbs with non-continuous fibular regeneration manifested ankle valgus. CONCLUSIONS: The non-vascularized fibula emerged as a relatively safe procedure in the long term with minimal affections of the knee, ankle, or tibial anatomy when longitudinal integrity of fibula was restored. The non-regenerations of the fibula may be prone to developing ankle valgus.

Surgical Scissors: The Core Surgical Instrument.

Surgical scissors form an essential part of both basic and specialty surgical sets. Their prime function is to cut tissues. They are also used for blunt dissection/development of tissue planes and piercing tissues. A wide variety of scissors are available for use in practice. This review article briefly describes common surgical scissors in orthopaedic use. The basic construct, biomechanics, types, their identification, specific uses, and care aspects are also discussed. A surgeon should be aware of the different types of scissors, their biomechanical features, and specific uses, as they are an important tool in his/her armamentarium. (Journal of Surgical Orthopaedic Advances 33(1):001-004, 2024).

Tissue proteome analysis for profiling proteins associated with lymph node metastasis in gallbladder cancer.

Lymph node (LN) metastasis is the earliest sign of metastatic spread and an established predictor of poor outcome in gallbladder cancer (GBC). Patients with LN positive GBC have a significantly worse survival (median survival- 7 months) than patients with LN negative disease (median survival- ~ 23 months) in spite of standard treatment which includes extended surgery followed by chemotherapy, radiotherapy and targeted therapy. This study aims at understanding the underlying molecular processes associated with LN metastasis in GBC. Here, we used iTRAQ-based quantitative proteomic analysis using tissue cohort comprising of primary tumor of LN negative GBC (n = 3), LN positive GBC (n = 4) and non-tumor controls (Gallstone disease, n = 4), to identify proteins associated with LN metastasis. A total of 58 differentially expressed proteins (DEPs) were found to be specifically associated with LN positive GBC based on the criteria of p value ≤ 0.05, fold change ≥ 2 and unique peptides ≥ 2. These include the cytoskeleton and associated proteins such as keratin, type II cytoskeletal 7 (KRT7), keratin type I cytoskeletal 19 (KRT19), vimentin (VIM), sorcin (SRI) and nuclear proteins such as nucleophosmin Isoform 1 (NPM1), heterogeneous nuclear ribonucleoproteins A2/B1 isoform X1 (HNRNPA2B1). Some of them are reported to be involved in promoting cell invasion and metastasis. Bioinformatic analysis of the deregulated proteins in LN positive GBC using STRING database identified 'neutrophil degranulation' and 'HIF1 activation' to be among the top deregulated pathways. Western blot and IHC analysis showed a significant overexpression of KRT7 and SRI in LN positive GBC in comparison to LN negative GBC. KRT7, SRI and other proteins may be further explored for their diagnostics and therapeutic applications in LN positive GBC.

Xanthogranulomatous cholecystitis with histologic features suggestive of IgG4 related cholecystitis - A morphologic overlap with IgG4 related disease.

AIMS: Both xanthogranulomatous cholecystitis (XGC) and IgG4-related cholecystitis (IgG4-CC) are rare chronic fibroinflammatory tumefactive diseases of the gallbladder, which cause a strong confusion with resectable malignancy in view of their mass forming tendency with extension into the liver. We aim to study the histopathologic features of xanthogranulomatous cholecystitis with regard to IgG4-related cholecystitis in extended cholecystectomy specimens. METHODS AND RESULTS: Sixty cases of extended cholecystectomy with liver wedge resection, diagnosed as XGC on histopathology from January 2018 to December 2021 were retrieved from the archives. Representative sections were reviewed by two pathologists independently. Immunohistochemistry was performed for IgG4 and IgG4/IgG was derived. The cases were dichotomized in two groups on the basis of IgG4 positive plasma cells. Six cases with >50 IgG4 positive plasma cells had storiform fibrosis, IgG4/IgG ratio >0.40 and extra-cholecystic extension. Of these, 50 % had obliterative phlebitis and 66.7 % had perineural plasma cell wrapping. CONCLUSIONS: A small subset of XGC cases (~10 %) had morphologic overlap with IgG4-CC, but should not be overcalled as the diagnosis of IgG4-RD requires an integrative approach based on clinical, serologic and imaging criteria and not solely on histopathology.

Efficacy of 2 Nonpharmaceutical (Non-nutritive Sucking and Human Care Contact) Pain Relief Measures for Idiopathic Clubfoot Casted Using Ponseti Technique.

PURPOSE: This study aimed at exploring the pain and physiological responses exhibited during Ponseti manipulation and casting in clubfoot infants. In addition, we compared the efficacy of 2 nonpharmaceutical techniques (non-nutritive sucking and human care contact) for tackling these responses. METHODS: The study included children with unilateral and bilateral idiopathic clubfeet between 15 days to 6 months of age. For comparisons, children were divided into control group without any intervention (group A), non-nutritive sucking group (group B), and human care contact group (group C). Pain score (Neonatal Infant Pain Score), heart rate (HR), and oxygen saturation (SpO2) was assessed before, during and 1 minute after casting. These measurements were compared using statistical methods. RESULTS: There were 16 children (11 bilateral) in group A, 17 (10 bilateral) in group B, and 18 (8 bilateral) in group C. Before casting, the baseline parameters (Neonatal Infant Pain Score, HR, and SpO2) of the 3 groups were comparable. Groups B and C had a significant reduction in pain score at casting and in postcasting period when compared with group A (P<0.05). Group B (at casting-mean: 174.1/min, postcasting-mean: 168.2/min) had the lowest HR both during and after cast application. Group B had the highest SpO2 among all the 3 groups, both during casting (mean: 95.7%) and after casting (mean: 97.4%) (P<0.05). CONCLUSIONS: Infants exhibit moderate pain response and altered physiological responses during and after Ponseti casting. Non-nutritive sucking emerged as a better method to lessen these parameters when compared with the conventional technique and human care contact. LEVEL OF EVIDENCE: Level II.

What exactly is "foot abduction" during management of idiopathic clubfoot in clinical practice?

PURPOSE: There is however gross ambiguity regarding the use of term "foot abduction" in clubfoot treatment. We measured below defined angles at different stages of clubfoot treatment to decipher their precise interpretation. METHODS: In a prospective evaluation of 25 unilateral clubfeet in infants' age less than six months treated with Ponseti technique, clinical leg foot and thigh foot angle were measured at talar head reduction (LHT0), pre-tenotomy, and post-tenotomy stage. A "normal" reference was available in the form of measurements of contralateral limb. RESULTS: Talar head (LHT0) was reduced at mean leg foot angle of 26 degrees. The corresponding pre- and post-tenotomy angles were 42.6 and 50.0 degrees, respectively. The reference leg foot angles for contralateral limb were 49.8 degrees. The thigh foot angle for LHT0, pre-tenotomy, post-tenotomy, and contralateral side were, respectively, 39.2, 56, 68, and 65.6 degrees. There was an additional tibial external rotation component of mean 13.4 degrees (SD 4.5) in the thigh foot angle when compared to the leg foot angle at tenotomy. This increased to 18 degrees (SD 3.4) post-tenotomy. CONCLUSIONS: The study suggested that the foot abduction described in the "Ponseti Manual" probably intends thigh foot rather than leg foot angles. There was a significant difference in the angles when talar head reduced and tenotomy was decided. The foot abduction is an ambiguous term which should be replaced by the more specific leg or thigh foot abduction angle.

Pain behavior of children with bilateral idiopathic clubfoot undergoing Ponseti casting and the effect of non-pharmaceutical pain-relieving agents.

INTRODUCTION: This study prospectively investigated the pain response and physiological parameters [heart rate (HR) and oxygen saturation (SpO2)] during sequential casting in bilateral clubfoot. Additionally, it explored the role of non-nutritive sucking and human care contact on the observed responses during casting. METHODS: Subjects were allotted to control group (Group A with no intervention) and two intervention groups (Group B: non-nutritive sucking intervention, Group C: human care contact intervention). Neonatal Infant Pain Score (NIPS), heart rate (HR), and oxygen saturation (SpO2) were used to assess the response. RESULTS: The three groups matched in age and gender characteristics of the participants. Pain response was noted across all groups. The left foot demonstrated a statistically significant preexisting tachycardia which rose further during casting (p < 0.01). Intergroup comparisons revealed that the alteration for NIPS during casting was in following sequence (Group A > C > B, p < 0.00001). The effect of interventions offered in Group B and C lasted in the post-cast period as well (B > C). CONCLUSION: The clubfoot child exhibited moderate pain response during casting of both feet. A tachycardia was noted prior to initiation of second cast which further exaggerated with subsequent cast. Pacifier (non-nutritive sucking) intervention produced better control of pain response than human care contact during casting for both feet.

Discovery of MDV6058 (PF-06952229), a selective and potent TGFßR1 inhibitor: Design, synthesis and optimization.

Compound 1 is a potent TGF-ß receptor type-1 (TGFßR1 or ALK5) inhibitor but is metabolically unstable. A solvent-exposed part of this molecule was used to analogue and modulate cell activity, liver microsome stability and mouse pharmacokinetics. The evolution of SAR that led to the selection of 2 (MDV6058 / PF-06952229) as a preclinical lead compound is described.

Bi-allelic POLR3A Loss-of-Function Variants Cause Autosomal-Recessive Wiedemann-Rautenstrauch Syndrome.

Wiedemann-Rautenstrauch syndrome (WRS), also known as neonatal progeroid syndrome, is a rare disorder of unknown etiology. It has been proposed to be autosomal-recessive and is characterized by variable clinical features, such as intrauterine growth restriction and poor postnatal weight gain, characteristic facial features (triangular appearance to the face, convex nasal profile or pinched nose, and small mouth), widened fontanelles, pseudohydrocephalus, prominent scalp veins, lipodystrophy, and teeth abnormalities. A previous report described a single WRS patient with bi-allelic truncating and splicing variants in POLR3A. Here we present seven additional infants, children, and adults with WRS and bi-allelic truncating and/or splicing variants in POLR3A. POLR3A, the largest subunit of RNA polymerase III, is a DNA-directed RNA polymerase that transcribes many small noncoding RNAs that regulate transcription, RNA processing, and translation. Bi-allelic missense variants in POLR3A have been associated with phenotypes distinct from WRS: hypogonadotropic hypogonadism and hypomyelinating leukodystrophy with or without oligodontia. Our findings confirm the association of bi-allelic POLR3A variants with WRS, expand the clinical phenotype of WRS, and suggest specific POLR3A genotypes associated with WRS and hypomyelinating leukodystrophy.

Identification and structure-activity relationship studies of small molecule inhibitors of the human cathepsin D.

Cathepsin D, an aspartyl protease, is an attractive therapeutic target for various diseases, primarily cancer and osteoarthritis. However, despite several small molecule cathepsin D inhibitors being developed, that are highly potent, most of them show poor microsomal stability, which in turn limits their clinical translation. Herein, we describe the design, optimization and evaluation of a series of novel non-peptidic acylguanidine based small molecule inhibitors of cathepsin D. Optimization of our hit compound 1a (IC50 = 29 nM) led to the highly potent mono sulphonamide analogue 4b (IC50 = 4 nM), however with poor microsomal stability (HLM: 177 and MLM: 177 µl/min/mg). To further improve the microsomal stability while retaining the potency, we carried out an extensive structure-activity relationship screen which led to the identification of our optimised lead 24e (IC50 = 45 nM), with an improved microsomal stability (HLM: 59.1 and MLM: 86.8 µl/min/mg). Our efforts reveal that 24e could be a good starting point or potential candidate for further preclinical studies against diseases where Cathepsin D plays an important role.

Laparoscopic versus open surgery for the management of post-cholecystectomy benign biliary strictures.

BACKGROUND AND AIM: Surgical management by a bilioenteric anastomosis is the standard for the repair of post-cholecystectomy benign biliary strictures (BBS). This is traditionally done as an open operation. There are a few reports describing the procedure by a laparoscopic technique. The aim of the present study was to describe our experience of laparoscopic bilio-enteric anastomosis [Roux-en-Y hepaticojejunostomy (LRYHJ)/laparoscopic hepaticoduodenostomy (LHD)] in the management of post-cholecystectomy BBS and compare the outcomes with our patients operated by the open approach. METHODS: Retrospective analysis of prospective data of post-cholecystectomy BBS patients treated by laparoscopic bilio-enteric anastomosis. The outcomes were compared with patients who underwent an open repair. RESULTS: Between January 2016 and February 2019, 63 patients underwent surgery for post-cholecystectomy BBS. Twenty-nine patients who underwent laparoscopic bilio-enteric anastomosis (LRYHJ-13, LHD-16) were compared with 34 patients who underwent an open repair. The median age (40 vs 39) years, type of index surgery [laparoscopic cholecystectomy (13 vs 15), laparoscopic converted to open cholecystectomy (10 vs 16), and open cholecystectomy (6 vs 3)], type of injury low stricture (7 vs 5) and high stricture (22 vs 29), preoperative biliary fistula (23 vs 30), and time from injury to repair (6 vs 7 months) were similar in the 2 groups. The median duration of surgery was also similar (210 vs 200 min, p = 0.937); however, the median intraoperative blood loss (50 mL vs 200 mL, p = 0.001), time to resume oral diet (2 vs 4 days p = 0.023),** and median duration of postoperative hospital stay (6 vs 8 days, p = 0.001) were significantly less in the laparoscopy group. Overall morbidity rate (within 30 days post-surgery) was significantly higher in the open repair group (38% vs 20%). In a subgroup analysis of the laparoscopic repair group, the operative time in patients who underwent an LHD was significantly less than LRYHJ (190 vs 230 min, p = 0.034). The other parameters like the mean intraoperative blood loss, time to initiate oral diet, duration of postoperative hospital stay, and incidence of postoperative bile leak were similar. Patients undergoing open repair had a median follow-up of 26 months with two developing anastomotic stenosis and those undergoing laparoscopic repair had a median follow-up for 9 months with one developing anastomotic stenosis. CONCLUSION: Laparoscopic surgery for post-cholecystectomy BBS with an LRYHJ or LHD is feasible and safe and compares favourably with the open approach.

Long-term outcomes of the Ponseti method for treatment of clubfoot: a systematic review.

PURPOSE: The Ponseti method has revolutionized the clubfoot treatment and has been adopted globally in the past couple of decades. However, most reported results of the Ponseti method are either short or midterm. Studies reporting long-term outcomes of the Ponseti method are limited. The following systematic review aimed to provide a comprehensive overview of the published articles on long-term outcomes of the Ponseti method. MATERIAL AND METHODS: A literature search was performed for articles published in electronic database PubMed (includes Medline) and Cochrane for broad keywords: "Clubfoot"; "Ponseti method/technique"; "long term outcomes/results." Studies selected included full-text articles in English language on children less than one year with primary idiopathic clubfoot treated by the Ponseti method with mean ten year follow-up. Non-idiopathic causes or syndromic clubfoot and case reports/review articles/meta-analyses were excluded. The following parameters were included for analysis: number of patients/clubfeet, male/female, mean age at treatment, mean/range of follow-up, relapses, additional surgery, range of motion, various outcome scores, and radiological variables. RESULTS: Fourteen studies with 774 patients/1122 feet were included. The male:female ratio was 2.4:1. Mean follow-up recorded in studies was 14.5 years. Relapses occurred in 47% patients with additional surgery being required in 79% patients with relapses. Of these, 86% of surgery were extra-articular while 14% were intra-articular. Plantigrade foot was achieved in majority patients with mean ankle dorsiflexion of 11 degrees. The outcome scores were in general good in contrast to radiological angles which were mostly outside normal range with talar flattening/navicular wedging/degenerative osteoarthritis changes occurring in 60%, 76%, and 30%, respectively. CONCLUSIONS: Long-term follow-up of infants with primary idiopathic clubfeet treated by the Ponseti method revealed relatively high relapse and additional surgery rates. Radiologically, the various angles were inconsistent compared to normal ranges and anatomical deformations/degenerative changes were present in treated feet. Moreover, the relapse rates and requirement of additional surgery increased on long-term follow-up. Despite this, majority feet were plantigrade and demonstrated good clinical results as measured by various outcome tools. There should be emphasis on long-term follow-up of children with clubfeet in view of late relapses and secondary late changes.

Immunoproteomics approach revealed elevated autoantibody levels against ANXA1 in early stage gallbladder carcinoma.

BACKGROUND: Early diagnosis is important for the timely treatment of gallbladder carcinoma (GBC) patients and may lead to increased survival outcomes. Here, we have applied serological proteome analysis (SERPA), an immunoproteomics approach, for the detection of 'tumor-associated antigens (TAAs) that elicit humoral response' in early stage GBC patients. METHODS: Total protein from pooled tumor tissue of GBC patients (n = 7) was resolved by two-dimensional gel electrophoresis (2-DE) followed by immunoblotting using pooled blood plasma from healthy volunteers (n = 11) or gallstone disease (GSD) cases (n = 11) or early stage GBC (Stage I and II) (n = 5) or GBC stage IIIA (n = 9). 2-D gel and immunoblot images were acquired and analyzed using PDQuest software to identify immunoreactive spots in GBC cases in comparison to controls. Proteins from immunoreactive spots were identified by liquid chromatography- tandem mass spectrometric analysis (LC-MS/MS). Autoantibody levels for two of the functionally relevant proteins were investigated in individual plasma samples (52 cases and 89 controls) by dot blot assay using recombinant proteins. RESULTS: Image analysis using PDQuest software identified 25 protein spots with significantly high or specific immunoreactivity in GBC cases. Mass spectrometric analysis of 8 corresponding protein spots showing intense immunoreactivity (based on densitometric analysis) in early stage GBC or GBC stage IIIA cases led to the identification of 27 proteins. Some of the identified proteins include ANXA1, HSPD1, CA1, CA2, ALDOA and CTSD. Among the two proteins, namely ANXA1 and HSPD1 verified using a cohort of samples, significantly elevated autoantibody levels against ANXA1 were observed in early stage GBC cases in comparison to healthy volunteers or GSD cases (unpaired t-test, p < 0.05). Receiver operating characteristic (ROC) curve analysis for ANXA1 showed an Area under the Curve (AUC) of 0.69, with 41.7% sensitivity against a specificity of 89.9% for early stage GBC. IHC analysis for ANXA1 protein showed 'high' expression levels in 72% of GBC cases whereas all the controls showed 'low' expression levels. CONCLUSIONS: The study suggests that the ANXA1 autoantibody levels against ANXA1 may be potentially employed for early stage detection of GBC patients. Other proteins could also be explored and verified in a large cohort of clinical samples.

Temporal Variation of Scores Along the Course of the Ponseti Treatment in Older Children: A Ready Guide to Progress of Treatment.

PURPOSE: We aimed to graphically study the correction trend along the course of Ponseti treatment in older children with idiopathic clubfeet. METHODS: The temporal variation of total Pirani and Dimeglio scores and their individual components at each casting session was represented graphically. Tenotomy correction was accounted for separately. We classified 0 to 4 as early, 4 to 8 as midlevel, and beyond 8 as late casts to describe the sequence of treatment. RESULTS: A total of 27 patients (39 feet; bilateral in 12) were studied. The average patient age was 4.78±2.36 years. Rigid equinus was the more severe pretreatment deformity in Pirani system and also the most difficult to treat component. Posterior crease and medial crease were least severe and were treated in early casts. Reducibility of lateral head of talus, curved lateral border of foot, and empty heel were moderately severe and showed a gradual improvement pattern over subsequent casting sessions. For Dimeglio components, equinus was the most resistant deformity, and it persisted until late casts. Adduction, rotation, and varus were moderately severe, and they followed a gradual improvement slope. Several components/scores did not turn 0 after correction for older clubfoot children. CONCLUSIONS: The treatment graphs for older clubfoot children adequately illustrated the initial severity, number of Ponseti casts used, correction of total scores and their individual components over sequential casting sessions, tenotomy influence, and the residual deformities.

Management of post septic sequelae of hips with dislocation in children.

BACKGROUND: Limited literature guide management of post septic sequelae of hips with dislocation in children. We studied the functional and radiological outcome of open reduction of such sequelae in 11 children. Special emphasis was given to determine the influence of surgical correction and relocation of these hips. METHODS: Preoperative acetabular index (AI) on both sides was compared to quantify acetabular dysplasia. Radiological parameters like AI, centre edge angle (CEA), Reimer's index, centre head distance discrepancy (CHDD) and neck shaft angle (NSA) were calculated and compared with the unintervened side at follow-up. Outcome was assessed radiologically by modified Severin classification and clinically by Moon's criterion. RESULTS: Average age at open reduction was 20.6 months and further follow-up was 48.8 months. The mean pre-operative AI on intervened side (35 degrees) differed significantly from unintervened side (22.5 degrees). The follow-up AI on intervened side (26.5 degrees) improved significantly from the pre-operative values but residual dysplasia persisted. Mean values for other radiological parameters on intervened side at follow-up were CEA 16.1 degrees, Reimer's index 31.5%, CHDD 18.6% and NSA 119 degrees. Mean shortening of 2.3 cm was documented in ten patients at final follow-up. Triradiate cartilage fused in four out of 11 hips at follow-up. Radiological outcome according to modified Severin classification was good to fair in seven patients (types II and III) whereas poor in four patients (types IV and V). Functional outcome as per Moon's criterion was excellent to good in nine patients, fair and poor in one patient each. CONCLUSIONS: Open reduction potentially alters the natural history of post septic sequelae of hips with dislocation and contributes to better hip mechanics and function.

Comparative evaluation of success of ultrasound-guided internal jugular vein cannulation using needle with guard: A randomized, controlled study.

BACKGROUND AND AIMS: We devised a guard which can be slid and fixed over the central venous puncture needle at a desired length (measured through ultrasound) preventing the needle from penetrating deeper into the skin beyond this guard. This randomized, single blinded, controlled study was designed to evaluate the success of ultrasound guided internal jugular vein (IJV) cannulation using measured guided needle with guard in terms of success and occurrence of complications. MATERIAL AND METHODS: After ethical approval and written informed consent from the patients ultrasound-guided right-sided IJV cannulation was done with a conventional puncture needle (length of 6.4 cm) in the control group (n = 210) and with a conventional puncture needle with a guard fixed proximal to the bevel at a distance equal to the distance between the skin entry point and the midpoint of IJV measured with the help of USG in the study group (n = 210). The primary outcome studied was the number of attempts for successful cannulation. The secondary outcomes studied were complications and ease of cannulation. RESULTS: 419 patients were randomized into control (n = 209) and study groups (210). Successful IJV cannulation in the first attempt (primary endpoint) in the study group was significantly higher compared to the control group (98.6 vs. 85.7%, P = 0.007). Posterior venous wall puncture was reduced in the study group, that is, 0.5% (1/210) compared to control group, that is, 8.61% (18/209) (P = 0.001). Common carotid artery puncture was 7.18% (15/209) in control group and 0% (0/210) in study group (P = 0.001). Operators rated better ease in study group (P < 0.001). CONCLUSIONS: The use of measured guided needle with guard significantly improved the accuracy, success and ease of USG guided IJV cannulation and decreased complications.

Insights into lipid accumulation in skeletal muscle in dysferlin-deficient mice.

Loss of dysferlin (DYSF) protein in humans results in limb-girdle muscular dystrophy 2B, characterized by progressive loss of muscles in the distal limbs with impaired locomotion. The DYSF-null (Bla/J) mouse develops severe steatotic muscles upon aging. Here, we report a marked increase in adipocytes, especially in the psoas and gluteus muscles but not in the soleus and tibialis anterior muscles in aged Bla/J mice compared with WT mice. There was a robust upregulation in the mRNA expression of enzymes involved in lipogenesis and triacylglycerol (TAG) synthesis pathways in the steatotic skeletal muscles. Lipidomic analysis of the steatotic skeletal muscles revealed an increase in several molecular species of TAG, although it is unclear whether it was at the expense of phosphatidylcholine and phosphatidylserine. The adipocytes in steatotic muscles were extramyocellular, as determined by the increased expression of caveolin 1 (a cellular marker for adipocytes) and lipid-droplet protein, perilipin 1. This increase in adipocytes occured as a consequence of the loss of myocytes.

Innovations in vascular access for hemodialysis.

Worldwide, hemodialysis remains the prevalent dialysis modality for more than 2 million patients who require well-functioning vascular access for this procedure. Creation of an arteriovenous fistula for long-term hemodialysis was the first innovation since the Scribner shunt and was followed by the development of an arteriovenous graft and catheter. Bioengineered vessels were developed during the last century, but this field has been energized by recent technology relating to the creation of human vessels. Novel endovascular techniques for creating an arteriovenous fistula may resolve some of the logistical issues involved in obtaining a timely arteriovenous fistula. Treatment of access stenosis, infection, and thrombosis has remained suboptimal, and innovative technologies are evolving. Many new approaches are now targeting the biological and mechanical aspects of vascular access, such as creation and maturation of arterial and venous anastomoses, development of a biological conduit for outflow, and negotiating the problems of central vein stenosis. Importantly, processes of access care that have long focused on arteriovenous fistulas are now recognizing the new paradigm, providing a complementary niche to arteriovenous grafts and dialysis catheters in the algorithm for individualized access placement. Cumulatively, to the credit of the multidisciplinary team approach, the long overdue focus on the very existential issue of vascular access for hemodialysis is being approached with newfound evidence-based enthusiasm as the vexing challenges related to regulations and reimbursement in hemodialysis persist. Patient choice and experience, often missed and ignored in the challenging management of an end-stage organ failure, need to stay central as we focus on patient-centered care of vascular access.

Avoiding problems in tunneled dialysis catheter placement.

Tunneled dialysis catheters (TDCs) remain the predominant vascular access for initiation of hemodialysis (HD) worldwide. TDCs are also utilized in a significant number of prevalent patients for continuation of dialysis and during the periods of complications related to arteriovenous (AV) accesses. TDC placement is a routine procedure, but can be associated with mechanical and infectious complications related to placement. Imaging guidance with ultrasound and fluoroscopy has made the placement of TDC safer and more successful. Adequate operator training, careful technique, utilization of a checklist, and barrier precautions are essential to avoid problems related to TDC placement.