Primary Hepatic Melanoma: A Diagnostic Surprise.

Melanoma is a relatively rare malignancy with a highly aggressive biological behavior. Metastases to other sites, like lymph nodes and liver are common, but primary hepatic melanoma is a rarity with poor survival ranging from months to few years. Diagnosis of primary hepatic melanoma via clinical features and imaging technology is difficult because of its ambiguous features. Here, we present a 26-year-old North Indian woman admitted in the department of gastrointestinal surgery at our tertiary care hospital with the complaint of pain in the abdomen for a month associated with the loss of appetite and subsequent weight loss. The liver function tests were within normal limits and viral markers were negative. The triple-phase computed tomography scan of abdomen showed significant hepatomegaly and two well-defined lesions in both lobes of the liver. Histopathological evaluation was performed on the core liver biopsies submitted from the liver lesions. A malignant tumor with abundant black intracytoplasmic pigment was identified. Immunohistochemistry proved the tumor to be melanoma. The detailed clinical history, laboratory, and radiological investigations were acquired and analyzed to rule out a metastatic lesion of the same. A final diagnosis of primary hepatic melanoma was thus rendered. Primary hepatic melanoma is extremely uncommon and has been rarely reported. Preoperative diagnosis is challenging due to low index of suspicion and nonspecific clinical features. In this case report, we discuss the clinicopathological features of primary hepatic melanoma and review the literature so as to increase the awareness and improve our understanding of the disease.

Regulated regeneration of adipose tissue in lipodystrophic Agpat2-null mice partially ameliorates hepatic steatosis.

Both humans and mice with congenital generalized lipodystrophy due to AGPAT2 deficiency develop diabetes mellitus, insulin resistance, and hepatic steatosis, which have been attributed to the near total loss of adipose tissue (AT). Here, we show that regulated AT regeneration in doxycycline (dox)-fed Tg-AT-hAGPAT2;mAgpat2-/- mice partially ameliorates hepatic steatosis at 12 weeks of age and causes reduced expression of genes involved in hepatic de novo lipogenesis despite partial (∼30-50%) AT regeneration compared to that in wild-type mice. Compared to chow-fed Tg-AT-hAGPAT2;mAgpat2-/- mice, those fed dox diet had markedly reduced serum insulin levels, suggesting an improvement in insulin resistance. Interestingly, the fasting plasma glucose levels in dox-fed Tg-AT-hAGPAT2;mAgpat2-/- mice were no different than those in chow-fed wild-type mice. Indirect calorimetry revealed normalization in the energy balance of dox-fed Tg-AT-hAGPAT2;mAgpat2-/- mice compared to that in chow-fed mice. This study's findings suggest that partial AT regeneration in lipodystrophic mice can ameliorate metabolic derangements.

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.

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.

Adipose-specific overexpression of human AGPAT2 in mice causes increased adiposity and mild hepatic dysfunction.

AGPAT2, a critical enzyme involved in the biosynthesis of phospholipids and triacylglycerol (TAG), is highly expressed in adipose tissue (AT). Whether overexpression of AGPAT2 in AT will result in increased TAG synthesis (obesity) and its metabolic complications remains unknown. We overexpressed human AGPAT2 specifically in AT using the adiponectin promoter and report increased mass of subcutaneous, gonadal, and brown AT in wild-type mice. Unexpectedly, overexpression of hAGPAT2 did not change the pattern of phospholipid or TAG concentration of the AT depots. Although there is an increase in liver weight, plasma aspartate aminotransferase, and plasma insulin at various time points of the study, it did not result in significant liver dysfunction. Despite increased adiposity in the Tg-AT-hAGPAT2;mAgpat2+/+ mice, there was no significant increase in TAG concentration of AT. Therefore, this study suggests a role of AGPAT2 in the generation of AT, but not for adipocyte TAG synthesis.

Early-onset diabetes mellitus as a presenting feature of Werner's syndrome in an Indian family.

BACKGROUND: Diabetes mellitus (DM) in children and adolescents is typically caused by type 1 DM, followed by type 2 DM and maturity-onset diabetes of the young (MODY). We report an unusual Asian Indian family in which three members presented with DM at ages 15, 20, and 30, but not fitting the typical clinical picture of type 1 DM, type 2 DM, or MODY. The primary objective was to elucidate the molecular genetic basis of DM in this family. METHODS: The proband, a 22-year-old man, had short stature, gray hair, osteoporosis, and markedly reduced subcutaneous fat on the body, especially on the extremities along with acanthosis nigricans, and developed myxoid malignant peripheral nerve sheath tumor. Detailed family history revealed multiple loops of consanguinity. The proband underwent whole-genome sequencing, and seven relatives underwent whole-exome sequencing. RESULTS: The proband and three additional family members were found to have the homozygous c.561A>G nucleotide variant of WRN RecQ-like helicase (WRN) gene consistent with the diagnosis of Werner's syndrome. The c.561A>G variant induces a new splicing site on exon 6 resulting in a truncated WRN protein, p.Lys187Trpfs*13. CONCLUSION: Our report brings to attention the onset of DM during childhood or early adulthood in patients with Werner's syndrome who typically develop type 2 DM around the age of 30-40 years. Presence of consanguinity among parents, dysmorphic features, and malignancy should prompt consideration of diagnosis of Werner's syndrome.

A case report of liver infiltration from a large renal cell carcinoma: Diagnostic and management enigma.

INTRODUCTION AND IMPORTANCE: Renal cell carcinoma is the most lethal malignancy of urinary tract. Invasion of right lobe of liver by Renal cell carcinoma is rare and possess a treatment challenge. Simultaneous nephrectomy with right hepatectomy has been proposed as a part of multi-modality treatment approach. But its safety and feasibility is not well established. CASE PRESENTATION: We herein discuss a case of 30-year old female patient who underwent simultaneous nephrectomy with right hepatectomy along with single peritoneal metastasectomy for a huge Renal cell carcinoma of right kidney and infiltrating the right lobe of liver. Intra-operatively a single peritoneal nodule was present which came positive for malignancy on frozen section. Considering young age, good performance status and oligometastatic disease definitive procedure in the form of combined right nephrectomy and right hepatectomy was performed. She was discharged from the hospital on 6th post-operative day with an uneventful post-operative course. CLINICAL DISCUSSION: The patients with locally advanced Renal cell carcinoma with involvement of adjacent organs require en block surgical resection in combination with targeted therapy and immunotherapy. The surgical management of patients with direct liver infiltration requires a right nephrectomy with some form of liver resection based on the extent of liver involvement to achieve a margin negative resection. In our case a plan of formal right hepatectomy was made as the tumor was infiltrating into segment VI, VII, and VIII. CONCLUSION: The combined nephrectomy and right hepatectomy is safe and feasible for this type of huge RCC invading right hepatic lobe.

Effect of Intensive Blood Pressure Control on Kidney Outcomes: Long-Term Electronic Health Record-Based Post-Trial Follow-Up of SPRINT.

BACKGROUND: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values. METHODS: SPRINT data were linked with EHR data from 49 (of 102) study sites. The primary outcome was the total slope of decline in eGFR for the intervention phase and the post-trial slope of decline during the observation phase using trial and outpatient EHR values. Secondary outcomes included a ≥30% decline in eGFR to <60 ml/min per 1.73 m 2 and a ≥50% decline in eGFR or kidney failure among participants with baseline eGFR ≥60 and <60 ml/min per 1.73 m 2 , respectively. RESULTS: EHR creatinine values were available for a median of 8.3 years for 3041 participants. The total slope of decline in eGFR during the intervention phase was -0.67 ml/min per 1.73 m 2 per year (95% confidence interval [CI], -0.79 to -0.56) in the standard treatment group and -0.96 ml/min per 1.73 m 2 per year (95% CI, -1.08 to -0.85) in the intensive treatment group ( P < 0.001). The slopes were not significantly different during the observation phase: -1.02 ml/min per 1.73 m 2 per year (95% CI, -1.24 to -0.81) in the standard group and -0.85 ml/min per 1.73 m 2 per year (95% CI, -1.07 to -0.64) in the intensive group. Among participants without CKD at baseline, intensive treatment was associated with higher risk of a ≥30% decline in eGFR during the intervention (hazard ratio, 3.27; 95% CI, 2.43 to 4.40), but not during the postintervention observation phase. In those with CKD at baseline, intensive treatment was associated with a higher hazard of eGFR decline only during the intervention phase (hazard ratio, 1.95; 95% CI, 1.03 to 3.70). CONCLUSIONS: Intensive BP lowering was associated with a steeper total slope of decline in eGFR and higher risk for kidney events during the intervention phase of the trial, but not during the postintervention observation phase.

Does Acetabulum Remodel Following Varus Derotation Osteotomy for Perthes' Disease?

Objective We investigated the effect of disease stage, patient's age and final contour of femoral head on acetabulum contour following varus derotation osteotomy of proximal femur (VDRO) in unilateral Perthes's disease. Methods The study is a retrospective analysis of case records of 23 children aged ≥6 years with unilateral Perthes' disease who underwent primary VDRO procedure for containment. Acetabular index (AI) and center edge angle (CEA) were calculated bilaterally in preoperative and follow-up radiographs and compared statistically. Results There were 15 boys and 8 girls. Six hips were in Ib, 8 in IIa and 9 in IIb modified Waldenström stage while undergoing VDRO. The mean age at surgical intervention was 8.7 years. The mean follow-up duration was 3.5 years. All femoral heads were healed at final follow-up and the final Stulberg grades were I = 3, II = 8, III = 7, IV = 5. A significant acetabular dysplasia on the affected side was present preoperatively. At follow-up, the patients operated had significantly raised AI and reduced CEA. There was no significant acetabular remodeling of the affected hips at follow-up even in children operated at younger age (< 8 years) or early stages (stage Ib or IIa). The acetabulum remodeling did not correspond to the final Stulberg grade as well. Conclusion Acetabulum was found involved in early stages of Perthes' disease. Varus derotation femoral osteotomy for the diseased hip showed no significant improvement in acetabular dysplasia even when operated in early disease stages or younger age group. Residual acetabular changes were also noted even with favorable Stulberg grades.

Regulated adipose tissue-specific expression of human AGPAT2 in lipodystrophic Agpat2-null mice results in regeneration of adipose tissue.

Genetic loss of Agpat2 in humans and mice results in congenital generalized lipodystrophy with near-total loss of adipose tissue and predisposition to develop insulin resistance, diabetes mellitus, hepatic steatosis, and hypertriglyceridemia. The mechanism by which Agpat2 deficiency results in loss of adipose tissue remains unknown. We studied this by re-expressing human AGPAT2 (hAGPAT2) in Agpat2-null mice, regulated by doxycycline. In both sexes of Agpat2-null mice, adipose-tissue-specific re-expression of hAGPAT2 resulted in partial regeneration of both white and brown adipose tissue (but only 30%-50% compared with wild-type mice), which had molecular signatures of adipocytes, including leptin secretion. Furthermore, the stromal vascular fraction cells of regenerated adipose depots differentiated ex vivo only with doxycycline, suggesting the essential role of Agpat2 in adipocyte differentiation. Turning off expression of hAGPAT2 in vivo resulted in total loss of regenerated adipose tissue, clear evidence that Agpat2 is essential for adipocyte differentiation in vivo.

Taurolidine/Heparin Lock Solution and Catheter-Related Bloodstream Infection in Hemodialysis: A Randomized, Double-Blind, Active-Control, Phase 3 Study.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) are one of the most prevalent, fatal, and costly complications of hemodialysis with a central venous catheter (CVC). The LOCK IT-100 trial compared the efficacy and safety of a taurolidine/heparin catheter lock solution that combines taurolidine 13.5 mg/ml and heparin (1000 units/ml) versus heparin in preventing CRBSIs in participants receiving hemodialysis via CVC. METHODS: LOCK IT-100 was a randomized, double-blind, active-control, multicenter, phase 3 study that enrolled adults with kidney failure undergoing maintenance hemodialysis via CVC from 70 US sites. Participants were randomized 1:1 to taurolidine/heparin catheter lock solution or heparin control catheter lock solution (1000 units/ml). The primary end point was time to CRBSI as assessed by a blinded Clinical Adjudication Committee. Secondary end points were catheter removal for any reason and loss of catheter patency. On the basis of a prespecified interim analysis, the Data and Safety Monitoring Board recommended terminating the trial early for efficacy with no safety concerns. RESULTS: In the full analysis population ( N =795), nine participants in the taurolidine/heparin arm ( n =397; 2%) and 32 participants in the heparin arm ( n =398; 8%) had a CRBSI. Event rates per 1000 catheter days were 0.13 and 0.46, respectively, with the difference in time to CRBSI being statistically significant, favoring taurolidine/heparin ( P < 0.001). The hazard ratio was 0.29 (95% confidence interval, 0.14 to 0.62), corresponding to a 71% reduction in risk of CRBSIs with taurolidine/heparin versus heparin. There were no significant differences between study arms in time to catheter removal for any reason or loss of catheter patency. The safety of taurolidine/heparin was comparable with that of heparin, and most treatment-emergent adverse events were mild or moderate. CONCLUSIONS: Taurolidine/heparin reduced the risk of developing a CRBSI in study participants receiving hemodialysis via CVC compared with heparin with a comparable safety profile. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Study Assessing Safety & Effectiveness of a Catheter Lock Solution in Dialysis Patients to Prevent Bloodstream Infection, NCT02651428 .

Limb length deceleration or coronal plane deformity correction using tension band plates: does plate configurations determine the intraarticular deformity of proximal tibia?

We studied whether the two-plate tension band configuration is more prone for intraarticular deformations than the single plate application used for coronal plane deformities (CPD). The study was based on radiological chart review (retrospective cross-sectional) of records of children [15 patients (30 plates) with limb length discrepancies (LLD) and 20 patients (36 plates) with CPD]. Interscrew angle, slope angle, and roof angle were compared in the initial postoperative and final radiographs to determine changes of tibial morphology. The mean patient age and follow up for the LLD and CPD groups respectively were 6.5 years, 39.8 months and 8.1 years, 15.5 months respectively. The interscrew angles widened between initial and final radiographs in the CPD group and for both sides in the LLD group. The initial and final slope angles were not significantly different in both LLD and CPD groups. Similar trend was observed for roof angle in either group. In the intergroup comparisons between LLD and CPD group, the slope angle of medial/lateral operated side in LLD group versus that of the operated side in CPD group matched statistically in the final radiographs. Similarly, the final roof angle in LLD and CPD groups was statistically similar. No significant intraarticular morphological change was demonstrated following tension band plating epiphysiodesis of the proximal tibia for our series involving young children. It was observed neither with the two-plate configuration used for limb length decelerations nor with the single plate application for coronal plane corrections.

Does Acetabulum Remodel Following Varus Derotation Osteotomy for Perthes' Disease? / O acetábulo sofre remodelamento após a osteotomia derrotatória varizante em pacientes com doença de Perthes?

Abstract Objective We investigated the effect of disease stage, patient's age and final contour of femoral head on acetabulum contour following varus derotation osteotomy of proximal femur (VDRO) in unilateral Perthes's disease. Methods The study is a retrospective analysis of case records of 23 children aged ≥6 years with unilateral Perthes' disease who underwent primary VDRO procedure for containment. Acetabular index (AI) and center edge angle (CEA) were calculated bilaterally in preoperative and follow-up radiographs and compared statistically. Results There were 15 boys and 8 girls. Six hips were in Ib, 8 in IIa and 9 in IIb modified Waldenström stage while undergoing VDRO. The mean age at surgical intervention was 8.7 years. The mean follow-up duration was 3.5 years. All femoral heads were healed at final follow-up and the final Stulberg grades were I = 3, II = 8, III = 7, IV = 5. A significant acetabular dysplasia on the affected side was present preoperatively. At follow-up, the patients operated had significantly raised AI and reduced CEA. There was no significant acetabular remodeling of the affected hips at follow-up even in children operated at younger age (< 8 years) or early stages (stage Ib or IIa). The acetabulum remodeling did not correspond to the final Stulberg grade as well. Conclusion Acetabulum was found involved in early stages of Perthes' disease. Varus derotation femoral osteotomy for the diseased hip showed no significant improvement in acetabular dysplasia even when operated in early disease stages or younger age group. Residual acetabular changes were also noted even with favorable Stulberg grades.

Resumo Objetivo Investigamos o efeito do estágio da doença, idade do paciente e contorno final da cabeça femoral no contorno do acetábulo após a osteotomia derrotatória varizante (VDRO) do fêmur proximal na doença de Perthes unilateral. Métodos O estudo é uma análise retrospectiva de prontuários de 23 crianças com idade ≥ 6 anos com doença de Perthes unilateral que foram submetidas ao procedimento primário de VDRO para contenção. O índice acetabular (AI) e o ângulo da borda central (CEA) foram calculados bilateralmente em radiografias pré-operatórias e de acompanhamento e submetidos à comparação estatística. Resultados Os pacientes eram 15 meninos e oito meninas. À VDRO, seis quadris estavam no estágio de Waldenström modificado Ib, oito no estágio IIa e nove no estágio IIb. A média de idade à intervenção cirúrgica foi de 8,7 anos. A duração média do acompanhamento foi de 3,5 anos. Todas as cabeças femorais estavam consolidadas no último acompanhamento e os graus finais de Stulberg foram I = 3, II = 8, III = 7 e IV = 5. Havia displasia acetabular significativa do lado acometido no período pré-operatório. No acompanhamento, os pacientes operados apresentaram elevação significativa de AI e redução de CEA. Não houve remodelamento acetabular significativo nos quadris acometidos durante o acompanhamento, mesmo em crianças operadas em idade menor (< 8 anos) ou estágios iniciais (estágio Ib ou IIa). O remodelamento do acetábulo também não correspondeu ao grau final de Stulberg. Conclusão A VDRO do fêmur do quadril acometido não levou à melhora significativa da displasia acetabular, mesmo quando a cirurgia foi realizada nos estágios iniciais da doença ou em pacientes mais jovens. Alterações acetabulares residuais também foram observadas mesmo com graus de Stulberg favoráveis.

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.

Post infective physeal bar sequelae around knee: Natural history and coronal plane deformities.

Background: and methodology: The presented retrospective study is a report of 17 children (18 limbs) with post infective physeal bars around the knee. Minimum 2 years follow up post sepsis follow up was available. Observations: The mean follow up post infection was 6.9 years. The bar formation manifested mean 22.6 months post sepsis. The angular deformity progressed at the mean monthly rate of 0.84, 0.1, 0.26° for peripheral, central and extensive bars respectively. Peripheral bars underwent early intervention. Balancing of physeal growth using contralateral '8' plate was useful for partial bars. For extensive bars and older patients, complete epiphyseodesis and limb length equalization was used. Articular abnormalities (cupping, flattening, small epiphysis) were associated in 80% bars. Neonatal infections were often multifocal and had articular abnormalities. Conclusions: The 3 bar types presented with different characteristics. Peripheral bars produced most angular deformities and required early intervention. Articular abnormalities were associated with physeal bars in large number of patients especially those with neonatal infections. Overall unhealthy physis beside bar, delayed manifestations, and limb length discrepancy should be accounted for while planning treatment.

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.

LTSI Consensus Guidelines: Preoperative Pulmonary Evaluation in Adult Liver Transplant Recipients.

The relationship between chronic liver disease and respiratory symptoms and hypoxia is well recognized. Over the last century, three pulmonary complications specific to chronic liver disease (CLD) have been characterized: hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. Apart from that coexisting pulmonary disease like chronic obstructive lung disease and interstitial lung disease also complicate the outcomes after liver transplantation (LT). Assessment for evaluation of underlying pulmonary disorders is essential to improve outcomes in patients with CLD, posted for LT. This consensus guideline of the Liver Transplant Society of India (LTSI) provides a comprehensive review of pulmonary issues in CLD, related and unrelated to underlying liver disease and gives recommendations for pulmonary screening in specific clinical scenarios in adults with chronic liver disease planned for LT. This document also aims to standardize the strategies for preoperative evaluation of these pulmonary issues in this subset of patients. Proposed recommendations were based on selected single case reports, small series, registries, databases, and expert opinion. The paucity of randomized, controlled trials in either of these disorders was noted. Additionally, this review will highlight the lacunae in our current evaluation strategy, challenges faced, and will provide direction to potentially useful futuristic preoperative evaluation strategies.

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.