Correlation Between Radiological and Functional Outcomes Following Operative and Nonoperative Management of Acetabular Fractures: A Prospective Observational Study.

INTRODUCTION: The management of acetabular fractures is a complicated orthopedic procedure that has been advancing with time. Newer radiological tools like CT scans help surgeons to identify and manage these fractures more attentively. The study was conducted to evaluate the clinical and radiographic outcomes in patients with acetabular fractures managed either conservatively or by open reduction and internal fixation. MATERIALS AND METHOD: The study was done on 35 patients aged 18-60 years, with acetabular fractures treated either surgically or conservatively. Clinical scorings and radiological scoring were only taken and noted at three- and six-month intervals using Matta's radiographic scoring and modified Merle d'Aubigne and Postel clinical hip scoring. Clinico-radiological variables and complications were compared between the two groups. The data obtained was subjected to statistical analyses using IBM Statistical Package of Social Sciences (SPSS) 2.0 version software (Chicago, IL, USA) at a level of significance being p<0.05. RESULTS:  Out of a total of 35 patients, 19 were treated surgically and 16 conservatively. In patients belonging to the surgical treatment group, a maximum of 57.9% were aged 40-50 years, whereas the maximum patients (50%) of the conservative treatment group were aged <40 years, with male predominance in both groups. The type of fracture was recorded according to Judet and Letournel in both groups. Merle d'Aubigne's scoring and Matta's hip score were recorded at three and six months in both groups. A positive correlation was seen between radiological and functional outcomes at three and six months, which means that the higher the radiological scoring, the better the functional outcome of the patient managed either conservatively or surgically in the entire cohort. CONCLUSION:  Our study revealed that surgically managed patients had better functional and radiological outcomes than the patients who were conservatively managed at six months of follow-up. However, this is associated with more complications depending on fracture complexity and initial presentation of hip dislocation. The higher the radiological scoring, the better the functional outcome of the patient managed either conservatively or surgically in the entire cohort.

Efficacy of Inclisiran in Patients Having Familial Hypercholesterolemia: Heterozygous Compared to Homozygous Trait, a Systematic Review and Meta-analysis.

OBJECTIVE: To find out whether inclisiran sodium has different efficacy in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) patient groups. METHODS: We conducted the systematic review and meta-analysis of ORION clinical trials. PubMed, Embase, and Clinicaltrials.gov databases were searched for the relevant studies. Atheroscalerotic parameters considered for our objective were low-density lipoprotein cholesterol, total cholesterol, proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B, and nonhigh-density lipoprotein cholesterol. Primary outcomes were the percentage difference in atheroscalerotic parameters at follow-up relative to baseline values. Our study examined these primary outcomes to determine whether there is a statistically significant difference between the HeFH and HoFH groups. Risk of bias was assessed by the Cochrane risk of bias tool. Meta-analysis was performed when at least 2 studies reported on the same variable. RESULTS: Four ORION clinical trials provided the data related to the mean difference in the atheroscalerotic parameters at follow-up relative to baseline, of HeFH and HoFH patient populations, after administration of 300 mg inclisiran subcutaneously. We pooled together these mean differences for each group and applied a statistical test to analyze if the values were significantly different between the groups. The results of our study unveiled the significant difference in pooled mean differences in low-density lipoprotein cholesterol (HeFH: -48.62%; HoFH: -9.12%; P < 0.05), total cholesterol (HeFH: -30.31%; HoFH: -11.50%; P < 0.05), apolipoprotein (HeFH: -39.97%; HoFH: -14.68%; P < 0.05), and nonhigh-density lipoprotein (HeFH: -44.51%; HoFH: -12.22%; P < 0.05) between HeFH and HoFH groups. However, the difference in pooled mean difference in PCSK9 values (HeFH: -68.41%; HoFH: -56.25%; P = 0.2) between HeFH and HoFH groups was statistically insignificant. Studies were of high quality. CONCLUSIONS: There was a significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of inclisiran except for PCSK9 parameter. Further studies are needed to support this conclusion.

Phase 3 RCT comparing docetaxel-platinum with docetaxel-platinum-5FU as neoadjuvant chemotherapy in borderline resectable oral cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF. METHODS: In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events. RESULTS: 495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95% CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P = 0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS was 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P < 0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P < 0.0001). CONCLUSION: NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival.

Incurable advanced salivary gland tumours: a retrospective analysis and peek into the perplexing clinical and molecular intricacies from a tertiary care centre in India.

Background: Salivary gland tumours are rare cancers with variable course and prognosis. There is a paucity of data, especially for the advanced stages. Materials and methods: This is a retrospective analysis carried out in our institute. All patients seeking treatment for incurable advanced salivary gland tumours from October 2018 to September 2022 were included. Relevant clinical data were collected and appropriate statistical analysis was applied. Results: 30 patients were included in the analysis. The parotid gland was the most common site of origin (73%). Adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC) were equally (37%) the most common pathological subtypes. The majority of patients were males (73%) and lungs (57%) were the most common site of metastases. On molecular analysis, SDC had high rates of androgen receptor (AR) (90%) and human epidermal growth factor receptor 2 (HER2) (55%) positivity. Mucoepidermoid carcinoma (MEC) had AR and HER2 positivity rates of 17% and 20%, respectively, while for ACC it was even lower. A variety of treatment regimens including hormonal therapy, anti-HER2 targeted therapy and chemotherapy were used in first-line treatment. With an overall response rate (ORR) of 10/21 (48%), only 9/21 (43%) went on to receive second-line treatment with an ORR of 4/9 (44%). The progression-free survival (PFS) with first-line treatment (PFS1) was a median of 5 months. The median PFS1 was worst for MEC. The median overall survival (OS) was 10 months. Median OS for ACC, SDC and MEC were 11, 10 and 7 months, respectively. At 24 months, ACC had much higher survival (50%) than others (10%) indicating a proportion of ACC with an indolent course. Conclusion: Our analysis highlights the variable disease biology of advanced salivary gland tumours and throws light on the various possible treatment targets and strategies. Molecular profiling and advancement in targeted therapies are expected to increase survival in this group of rare cancers.

Management of non-functioning kidney due to pelvi-ureteric junction obstruction in pediatric age group: an observational study.

INTRODUCTION: A non-functional kidney (NFK) has been defined as one having paper-thin parenchyma, and split renal function (SRF) of < 10% on a nuclear scan. There are differences of opinion about nephrectomy or pyeloplasty in these patients. The present study was conducted to assess our management strategy of renal salvage for NFK. MATERIALS AND METHODS: It was a retrospective cohort study from January 2015 to July 2022, patients having SRF < 10% were included. These patients underwent ultrasound-guided percutaneous nephrostomy (PCN). A repeat nuclear scan was performed after 3 months. If SRF increased to > 10%, pyeloplasty was performed. RESULTS: Fifteen patients were managed. The mean age was 24.67 ± 23.61 months. Male to female ratio was 4:1. The initial mean SRF was 6.67 ± 2.85, which improved to 16.80 ± 4.69 after 3 months of placing the PCN (p < 0.001). The corresponding changes in the mean effective renal plasma flow (ERPF) were 60.13 ± 24.08 to 106.53 ± 24.61 (p < 0.001). There was no complaint after the placement of PCN. All patients underwent dismembered pyeloplasty. CONCLUSION: In NFK due to PUJO, expectant treatment in form of PCN followed by pyeloplasty appears to be the primary treatment modality, and nephrectomy may not be needed in any of them.

Results of Phase III Randomized Trial for Use of Docetaxel as a Radiosensitizer in Patients With Head and Neck Cancer, Unsuitable for Cisplatin-Based Chemoradiation.

PURPOSE: There is a lack of published literature on systemic therapeutic options in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing chemoradiation. Docetaxel was assessed as a radiosensitizer in this situation. METHODS: This was a randomized phase II/III study. Adult patients (age ≥ 18 years) with LAHNSCC planned for chemoradiation and an Eastern Cooperative Oncology Group performance status of 0-2 and who were cisplatin-ineligible were randomly assigned in 1:1 to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). RESULTS: The study recruited 356 patients between July 2017 and May 2021. The 2-year DFS was 30.3% (95% CI, 23.6 to 37.4) versus 42% (95% CI, 34.6 to 49.2) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.673; 95% CI, 0.521 to 0.868; P value = .002). The corresponding median overall survival (OS) was 15.3 months (95% CI, 13.1 to 22.0) and 25.5 months (95% CI, 17.6 to 32.5), respectively (log-rank P value = .035). The 2-year OS was 41.7% (95% CI, 34.1 to 49.1) versus 50.8% (95% CI, 43.1 to 58.1) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.747; 95% CI, 0.569 to 0.980; P value = .035). There was a higher incidence of grade 3 or above mucositis (22.2% v 49.7%; P < .001), odynophagia (33.5% v 52.5%; P < .001), and dysphagia (33% v 49.7%; P = .002) with the addition of docetaxel. CONCLUSION: The addition of docetaxel to radiation improved DFS and OS in cisplatin-ineligible patients with LAHNSCC.[Media: see text].

Low-Dose Immunotherapy in Head and Neck Cancer: A Randomized Study.

PURPOSE: The regimens approved for the treatment of advanced head and neck squamous cell carcinoma are accessible to only 1%-3% of patients in low- and middle-income countries because of their cost. In our previous study, metronomic chemotherapy improved survival in this setting. Retrospective data suggest that a low dose of nivolumab may be efficacious. Hence, we aimed to assess whether the addition of low-dose nivolumab to triple metronomic chemotherapy (TMC) improved overall survival (OS). METHODS: This was a randomized phase III superiority study. Adult patients with recurrent or newly diagnosed advanced head and neck squamous cell carcinoma being treated with palliative intent with an Eastern Cooperative Oncology Group performance status of 0-1 were eligible. Patients were randomly assigned 1:1 to TMC consisting of oral methotrexate 9 mg/m2 once a week, celecoxib 200 mg twice daily, and erlotinib 150 mg once daily, or TMC with intravenous nivolumab (TMC-I) 20 mg flat dose once every 3 weeks. The primary end point was 1-year OS. RESULTS: One hundred fifty-one patients were randomly assigned, 75 in TMC and 76 in the TMC-I arm. The addition of low-dose nivolumab led to an improvement in the 1-year OS from 16.3% (95% CI, 8.0 to 27.4) to 43.4% (95% CI, 30.8 to 55.3; hazard ratio, 0.545; 95% CI, 0.362 to 0.820; P = .0036). The median OS in TMC and TMC-I arms was 6.7 months (95% CI, 5.8 to 8.1) and 10.1 months (95% CI, 7.4 to 12.6), respectively (P = .0052). The rate of grade 3 and above adverse events was 50% and 46.1% in TMC and TMC-I arms, respectively (P = .744). CONCLUSION: To our knowledge, this is the first-ever randomized study to demonstrate that the addition of low-dose nivolumab to metronomic chemotherapy improved OS and is an alternative standard of care for those who cannot access full-dose checkpoint inhibitors.

Angiotensin-converting Enzyme Inhibitors: Can it be a Potential Treatment of Infantile Hemangioma.

AIMS: The aim of the sudy was to evaluate potential role of oral captopril, an angiotensin-converting enzyme (ACE) inhibitor, and in treatment of infantile hemagioma (IH) and report our preliminary results. METHODS: This prospective study included 18 children with IH admitted in the department of pediatric surgery with no history of prior treatment of any type. Baseline blood pressure (BP), electrocardiogram, two-dimensional echocardiography, serum electrolytes, and renal function test (RFT) were noted. Oral captopril was started as first-line drug at a dose of 0.1 mg/kg orally 12 h with gradually increase of dosage up to 2.0 mg/kg 12 h over the period of 10 days with monitoring of BP, serum electrolytes, RFT, and occurrence of any side effect. If no side effects were noted and patients were stable, they were discharged and followed up until 6 months after stopping treatment. During follow-up, response to treatment was documented clinically and photographically. Development of any side effect was also noted. RESULTS: Excellent response to captopril was noticed in nine patients over 16-18 months. Four patients showed good response. Oral propranolol had to be administered alternatively in one patient showing fair response during the initial 4 months but no response afterward and in four patients showing no response at all. One patient developed an allergic reaction to propranolol and was started oral corticosteroid. These five patients had near complete resolution of lesion for the next 8-10 months. CONCLUSIONS: ACE inhibitors might have a role, though slow, in the involution of IHs. Therefore, these may have the potential to emerge as an alternative treatment for IH in future after confirmation with randomized studies with propranolol.

Supernumerary Kidney Associated With Horseshoe Malformation and Ureteric Stricture With Hydroureteronephrosis - A Rare Case.

Supernumerary kidney is an accessory kidney with its own vasculature, collecting-system and encapsulated parenchyma with about 100 cases reported in the literature. However, there is no report of supernumerary kidney associated with horseshoe malformation with ureteric stricture. We report a rare case of 20 months old female admitted with left-sided abdomen lump and mild abdominal pain. During surgery, supernumerary kidney with horseshoe component with grossly-dilated left-sided pelvicalyceal system and proximal 1-cm of left-ureter, distal to which whole of left-ureter was noncanalized, was seen. Right-ureter was normal. Distal dilated part of left-ureter was anastomosed to bladder-dome after excision of strictured segment of left-ureter with placement of nephrostomy.

Neo-adjuvant chemotherapy followed by either continuous hyper-fractionated accelerated radiation therapy week-end less or conventional chemo-radiotherapy in locally advanced NSCLC-A randomised prospective single institute study.

CONTEXT: Better locoregional control and increased overall survival by continuous hyper fractionated accelerated radiotherapy have been shown in unresectable nonsmall cell lung carcinoma (NSCLC). Dose escalation and neoadjuvant chemotherapy (NACT) along with continuous hyperfractionated accelerated radiotherapy week end-less (CHARTWEL) were also tried for improved survival. In this present study, we compared the results of NACT followed by CHARTWEL against NACT followed by conventional concurrent chemo-radiation therapy. AIMS: The aim of this study is to compare the locoregional control and toxicities in NSCLC Stage IIIA and B in both arms. SETTINGS AND DESIGN: Randomized, prospective single-institutional study with a study population comprising all locally advanced unresectable NSCLC patients enrolled in 2014 at our institute. SUBJECTS AND METHODS: All enrolled patients were randomized into two arms-CHARTWEL and concomitant chemo-radiotherapy (CCRT), after three weeks of the fourth cycle of NACT. In CHARTWEL arm 30 patients received two-dimensional radiotherapy (RT) 58.5 Gy/39 fr/2.5 weeks while in CCRT arm 30 received 66 Gy/33 fr/6.5 weeks. Disease response was evaluated at 6 months and toxicity assessment during and after treatment completion. Data were analyzed using tools such as percentage, mean, Chi-square test and P value. Chi-square and P value was calculated by statistical online software (http://quantpsy.org). RESULTS: 28% of patients in study arm and 20% in control arm had complete response at 6 months after RT. Locoregional disease control was observed in 44% in study arm and 32% in control arm of patients. There was no statistical difference in grades of toxicities or overall survival (OS)/disease-free survival except persistent esophagitis Grade III seen in two patients of study arm. CONCLUSIONS: Study suggests that CHARTWEL in combination with NACT is an effective strategy to treat patients with locally advanced lung cancer with the advantage of a smaller dose and shorter duration. Although large multivariate studies still needed.

Low-cost oral metronomic chemotherapy versus intravenous cisplatin in patients with recurrent, metastatic, inoperable head and neck carcinoma: an open-label, parallel-group, non-inferiority, randomised, phase 3 trial.

BACKGROUND: Regimens for palliation in patients with head and neck cancer recommended by the US National Comprehensive Cancer Network (NCCN) have low applicability (less than 1-3%) in low-income and middle-income countries (LMICs) because of their cost. In a previous phase 2 study, patients with head and neck cancer who received metronomic chemotherapy had better outcomes when compared with those who received intravenous cisplatin, which is commonly used as the standard of care in LMICs. We aimed to do a phase 3 study to substantiate these findings. METHODS: We did an open-label, parallel-group, non-inferiority, randomised, phase 3 trial at the Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India. We enrolled adult patients (aged 18-70 years) who planned to receive palliative systemic treatment for relapsed, recurrent, or newly diagnosed squamous cell carcinoma of the head and neck, and who had an Eastern Cooperative Oncology Group performance status score of 0-1 and measurable disease, as defined by the Response Evaluation Criteria In Solid Tumors. We randomly assigned (1:1) participants to receive either oral metronomic chemotherapy, consisting of 15 mg/m2 methotrexate once per week plus 200 mg celecoxib twice per day until disease progression or until the development of intolerable side-effects, or 75 mg/m2 intravenous cisplatin once every 3 weeks for six cycles. Randomisation was done by use of a computer-generated randomisation sequence, with a block size of four, and patients were stratified by primary tumour site and previous cancer-directed treatment. The primary endpoint was median overall survival. Assuming that 6-month overall survival in the intravenous cisplatin group would be 40%, a non-inferiority margin of 13% was defined. Both intention-to-treat and per-protocol analyses were done. All patients who completed at least one cycle of the assigned treatment were included in the safety analysis. This trial is registered with the Clinical Trials Registry-India, CTRI/2015/11/006388, and is completed. FINDINGS: Between May 16, 2016, and Jan 17, 2020, 422 patients were randomly assigned: 213 to the oral metronomic chemotherapy group and 209 to the intravenous cisplatin group. All 422 patients were included in the intention-to-treat analysis, and 418 patients (211 in the oral metronomic chemotherapy group and 207 in the intravenous cisplatin group) were included in the per-protocol analysis. At a median follow-up of 15·73 months, median overall survival in the intention-to-treat analysis population was 7·5 months (IQR 4·6-12·6) in the oral metronomic chemotherapy group compared with 6·1 months (3·2-9·6) in the intravenous cisplatin group (unadjusted HR for death 0·773 [95% CI 0·615-0·97, p=0·026]). In the per-protocol analysis population, median overall survival was 7·5 months (4·7-12·8) in the oral metronomic chemotherapy group and 6·1 months (3·4-9·6) in the intravenous cisplatin group (unadjusted HR for death 0·775 [95% CI 0·616-0·974, p=0·029]). Grade 3 or higher adverse events were observed in 37 (19%) of 196 patients in the oral metronomic chemotherapy group versus 61 (30%) of 202 patients in the intravenous cisplatin group (p=0·01). INTERPRETATION: Oral metronomic chemotherapy is non-inferior to intravenous cisplatin with respect to overall survival in head and neck cancer in the palliative setting, and is associated with fewer adverse events. It therefore represents a new alternative standard of care if current NCCN-approved options for palliative therapy are not feasible. FUNDING: Tata Memorial Center Research Administration Council. TRANSLATIONS: For the Hindi, Marathi, Gujarati, Kannada, Malayalam, Telugu, Oriya, Bengali, and Punjabi translations of the abstract see Supplementary Materials section.

Study of Thoracoscopic Repair of Diaphragmatic Eventration in Children: A Case Series.

Background: To present a case series of children with eventration of diaphragm who underwent thoracoscopic repair highlighting the technical points and surgical modifications to prevent a recurrence. Settings and Design: This is an observational study of patients with diaphragmatic eventration admitted to a tertiary care institute. The study was designed following CARE guidelines endorsed by EQUATOR Network. Pediatric patients who had undergone thoracoscopic repair between January 2010 and March 2019 were included in the study. Materials and Methods: Age at surgery, gender, weight, site of the lesion, operating time, need for postoperative drain, and complications were assessed. Results: Twenty-six patients had thoracoscopic repair of the eventration of diaphragm. The male-female ratio was 12:1 and mean weight at the time of surgery was 6.3 kg (2.2-22 kg) with most patients having left side congenital diaphragmatic eventration (n = 21) as compared with the right side (n = 5). The average operating time was 66 minutes (37-144 minutes). Conclusions: Diaphragm plication by a thoracoscopic approach is safe and feasible in neonates and pediatric patients.

Availability and Quality of Online Information on Sub-Internships in U.S. Orthopaedic Residency Programs.

BACKGROUND: The purpose of the present study was to assess the availability and quality of online information regarding sub-internships in orthopaedics among U.S. orthopaedic residency programs. METHODS: Each U.S. orthopaedic surgery residency program web site was assessed for the following 4 criteria: any mention of a sub-internship offered by that program, contact information regarding the sub-internship, a list of learning objectives to be met by the rotating student during the sub-internship, and presence of a web page dedicated solely to the orthopaedic sub-internship. Each web site was given a sub-internship score (SI score) from 0 to 4 based on how many of the above criteria were met. RESULTS: From the 151 analyzed U.S. orthopaedic surgery residency program web sites, 69 (46%) did not have any mention of a sub-internship and thus received a score of 0, 4 (3%) received a score of 1, 18 (12%) received a score of 2, 20 (13%) received a score of 3, and 40 (26%) received a score of 4. The average SI score was 1.05 for the community-based orthopaedic residency programs, compared with 1.98 for the university-based orthopaedic programs (p = 0.003). Subgroup analysis based on SI scores (0 vs. 1 to 4) revealed that the higher-score group (1 to 4) had a higher percentage of university-based programs than the lower-score (0) group (80% vs. 62%; p = 0.003) and was associated with a greater number of residents per program than the lower-score group (mean, 26.4 vs. 21.0; p = 0.04). There was a weak association between the SI score and the number of residents in a given program (R2 = 0.074, p = 0.0004). CONCLUSIONS: The availability and quality of online information regarding sub-internships offered at orthopaedic residency programs in the U.S. are variable. Nearly half of the programs did not have any available online information on their web sites regarding orthopaedic surgery sub-internships. Larger and university-based orthopaedic programs have more robust information regarding sub-internships than smaller and community-based programs. CLINICAL RELEVANCE: There needs to be greater awareness and more uniformly accessible online information regarding orthopaedic surgery sub-internships for senior medical students seeking elective orthopaedic rotations prior to applying for residency training.

Yield of endoscopic ultrasound-guided fine needle aspiration for subcentimetric lymph nodes: A comparison to larger nodes.

BACKGROUND AND OBJECTIVES: Subcentimetric (defined as <1 cm at short axis) lymph nodes are considered benign and there is limited literature on the results of fine needle aspiration (FNA) of these nodes. METHODS: Endoscopic ultrasound (EUS) guided FNA was done on 189 lymph nodes in 166 patients with pyrexia of unknown origin (n = 113) or malignancy (n = 53). Subcentimetric lymph nodes (Group A) were compared to nodes with short axis diameter ≥1 cm (Group B). Data are shown as number, percentage, and median (25-75 interquartile range). RESULTS: There was no significant difference between Group A and Group B regarding site of lymph nodes (mediastinal in 73.6 and 72.5%, abdominal in 26.3 vs. 27.4%), number of slides (median 14 vs. 15), needle passes (median 2), and needle used (22 G needle in 85.5% vs. 69.9%). Group A had significantly lesser long axis diameter (1.5 [1.2-2] vs. 2.1 [1.6-2.9] cm) and short axis diameter (0.7 [0.6-0.8) vs. 1.4 [1.1-1.6] cm). A diagnosis (pathologic or reactive) could not be made in 2 (2.6%) and 11 (9.7%) lymph nodes in Group A and Group B, respectively (P = 0.078), due to inadequate material. Respective diagnoses in Group A and Group B were reactive lymphadenopathy (51.3% vs. 18.5%, P = 0.000), granulomatous lymphadenopathy (34.2% vs. 53%, P = 0.011), and malignancy (11.8% vs. 18.5%, P = 0.231). The lymph nodes with granulomatous and malignant change were significantly larger and had higher chances of having sharply demarcated borders as compared to reactive nodes. CONCLUSION: EUS-guided FNA of subcentimetric lymph nodes have comparable results to larger nodes. Almost half of the subcentimetric lymph nodes are pathologic.

Retracted Publications in Orthopaedics: Prevalence, Characteristics, and Trends.

BACKGROUND: Retracted publications are a crucial, yet overlooked, issue in the scientific community. The purpose of our study was to assess the prevalence, characteristics, and trends of retracted publications in the field of orthopaedics. METHODS: Five databases were utilized to identify retracted publications in orthopaedics. The cited articles were assessed for various characteristics, including reason for retraction, based on the Committee on Publication Ethics (COPE) guidelines and trends over time. RESULTS: From 1984 to June 4, 2016, 59 of 229,502 orthopaedic publications were retracted (3 per 10,000 articles). There was a spike in the prevalence (22 of 59) of retracted articles in 2015. When compared with the total number of retracted publications identified through PubMed, the field of orthopaedics represented 1.4% of all retracted publications. The original version of 47 of these 59 retracted publications was still available on the respective journal's web site; 14 (30%) of these were not noted as having been retracted. The mean time from electronic publication to retraction was 19.4 ± 23.3 months. The mean number of citations of a retracted publication after the date of retraction was 9.3 ± 19.3. Reasons for retraction included plagiarism (32%), misconduct (27%), redundant publication (22%), miscalculation or experimental error (8%), and unethical research (0%); the reason for retraction was not stated for 10% of the publications. There was no correlation between a journal's impact factor and the mean number of months to retraction (p = 0.564). CONCLUSIONS: While uncommon, the retraction of publications within the field of orthopaedics may be increasing. The most often cited reasons for retraction were plagiarism, misconduct, and redundant publication. Retracted articles continue to be cited in the literature after retraction. CLINICAL RELEVANCE: Greater awareness of the COPE guidelines within the orthopaedic community and more efficient means to prevent the citation of retracted articles are needed.

Epigenetics in Reactive and Reparative Cardiac Fibrogenesis: The Promise of Epigenetic Therapy.

Epigenetic changes play a pivotal role in the development of a wide spectrum of human diseases including cardiovascular diseases, cancer, diabetes, and intellectual disabilities. Cardiac fibrogenesis is a common pathophysiological process seen during chronic and stress-induced accelerated cardiac aging. While adequate production of extracellular matrix (ECM) proteins is necessary for post-injury wound healing, excessive synthesis and accumulation of extracellular matrix protein in the stressed or injured hearts causes decreased or loss of lusitropy that leads to cardiac failure. This self-perpetuating deposition of collagen and other matrix proteins eventually alter cellular homeostasis; impair tissue elasticity and leads to multi-organ failure, as seen during pathogenesis of cardiovascular diseases, chronic kidney diseases, cirrhosis, idiopathic pulmonary fibrosis, and scleroderma. In the last 25 years, multiple studies have investigated the molecular basis of organ fibrosis and highlighted its multi-factorial genetic, epigenetic, and environmental regulation. In this minireview, we focus on five major epigenetic regulators and discuss their central role in cardiac fibrogenesis. Additionally, we compare and contrast the epigenetic regulation of hypertension-induced reactive fibrogenesis and myocardial infarction-induced reparative or replacement cardiac fibrogenesis. As microRNAs-one of the major epigenetic regulators-circulate in plasma, we also advocate their potential diagnostic role in cardiac fibrosis. Lastly, we discuss the evolution of novel epigenetic-regulating drugs and predict their clinical role in the suppression of pathological cardiac remodeling, cardiac aging, and heart failure. J. Cell. Physiol. 232: 1941-1956, 2017. © 2016 Wiley Periodicals, Inc.

A small molecule inhibitor of PAI-1 protects against doxorubicin-induced cellular senescence.

Doxorubicin, an anthracycline antibiotic, is a commonly used anticancer drug. In spite of its widespread usage, its therapeutic effect is limited by its cardiotoxicity. On the cellular level, Doxorubicin-induced cardiotoxicity manifests as stress induced premature senescence. Previously, we demonstrated that plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of serine proteases, is an important biomarker and regulator of cellular senescence and aging. Here, we tested the hypothesis that pharmacological inhibition of cellular PAI-1 protects against stress- and aging-induced cellular senescence and delineated the molecular basis of protective action of PAI-1 inhibition. Results show that TM5441, a potent small molecule inhibitor of PAI-1, effectively prevents Doxorubicin-induced senescence in cardiomyocytes, fibroblasts and endothelial cells. TM5441 exerts its inhibitory effect on Doxorubicin-induced cellular senescence by decreasing reactive oxygen species generation, induction of antioxidants like catalase and suppression of stress-induced senescence cadre p53, p21, p16, PAI-1 and IGFBP3. Importantly, TM5441 also reduces replicative senescence of fibroblasts. Together these results for the first time demonstrate the efficacy of PAI-1 inhibitor in prevention of Doxorubicin-induced and replicative senescence in normal cells. Thus PAI-1 inhibitor may form an important adjuvant component of chemotherapy regimens, limiting not only Doxorubicin-induced cardiac senescence but also ameliorating the prothrombotic profile.

Liver Transplantation for Alcohol-Related Liver Disease.

Alcoholic liver disease (ALD) is a common indication for liver transplantation. It is a much debated indication for deceased donor liver transplantation due to organ shortage and potential of alcohol relapse after liver transplantation. A six-month abstinence before liver transplantation is required at most centers to decrease chances of alcohol relapse after liver transplantation. However, this rule is not relevant for patients with severe alcoholic hepatitis or severely decompensated patients who are unlikely to survive till 6 months. Long-term care of these patients after liver transplantation includes assessment of relapse, smoking, and surveillance of de novo malignancies. Current review discusses role of abstinence, factors affecting alcohol relapse, liver transplantation for alcoholic hepatitis, role of living donor liver transplantation, and long-term care of ALD patients who undergo liver transplantation.