Role of Inferior Vena Cava Collapsibility Index in the Prediction of Hypotension Associated With Central Neuraxial Block: A Prospective Observational Study.

BACKGROUND: There are only a few studies on perioperative use of inferior vena cava collapsibility index (IVCCI) to predict hypotension after anesthesia. The study aimed to evaluate IVCCI as predictor of hypotension in patients receiving central neuraxial block (CNB) for elective surgery. METHOD: One hundred patients of ASA grade I/II, aged 18-60 years undergoing elective surgery under CNB were enrolled. Ultrasound IVC examination was performed preoperatively and the patients were allocated to Group C (Collapsing group: IVCCI ≥50%) or Group NC (Non-Collapsing group: IVCCI <50%). Thereafter, in the operation theatre, the patient was given CNB and observed for development of hypotension. The hypotension was treated with additional fluid bolus (5 mL kg-1 over 10 minutes) and/or vasopressor (mephentramine 6 mg IV). The primary objective was to compare the incidence of hypotension; the secondary objective was to compare the fluid and vasopressor requirement in the Groups C and NC. RESULT: Six patients were excluded from study due to poor visualization of IVC. The mean IVCCI for Group C (n = 53) was 56.06 ± 4.62% and Group NC (n = 41) was 34.01 ± 8.94%. The incidence of hypotension was 56.60% (20/53) in Group C and 4.87% (2/41) in Group NC (P < .001). The vasopressor and fluid requirement was also statistically significantly higher in Group C compared with Group NC (P < .001). CONCLUSION: Preoperative ultrasound assessment of IVCCI is useful in predicting hypotension after CNB in patients receiving CNB for elective surgery.

Analgesic efficacy of ultrasound-guided transversus abdominis plane block for laparoscopic gynecological surgery: a randomized controlled trial.

BACKGROUND: This study aimed to determine whether ultrasound-guided transversus abdominis plane (TAP) block is more effective in reducing postoperative pain and analgesic consumption than local anesthetic infiltration (LAI) at the port site for elective laparoscopic gynecological surgeries. METHODS: Eighty patients with the American Society of Anesthesiologists status I/II undergoing laparoscopic gynecology surgery were enrolled for this randomized control trial. After general anesthesia was administered, patients in group C received LAI at each port site, and patients in group T received bilateral ultrasound-guided TAP. Postoperative pain was assessed at time intervals of 1/2, 2, 4, 6, 8, and 24 h using the numeric pain scale (NPS). Clinical metrics such as postoperative analgesic diclofenac consumption, need for rescue fentanyl, nausea-vomiting scores, and antiemetic requirements were also recorded. RESULTS: Seventy-four patients were included in the final analysis. Postoperatively, patients in group T had significantly lower NPS than those in group C (P < 0.05). The highest difference in the postoperative NPS was observed at 2 h (median [1Q, 3Q]; group C = 3 [2, 4]; group T = 1 [0, 2]; P < 0.001). A statistically significant difference was observed in the frequency of diclofenac (75 mg intravenous) requirement between the groups (P = 0.010). No significant difference was observed between the groups in need of rescue fentanyl or antiemetic and the nausea-vomiting scores. CONCLUSIONS: In patients undergoing laparoscopic gynecological surgery, ultrasound-guided TAP block provided greater postoperative analgesic benefits in terms of lower NPS and reduced analgesic requirements than port site LAI.

Evaluation of postoperative analgesia of erector spinae plane block in elective laparoscopic cholecystectomy: a randomized controlled trial.

BACKGROUND: Only a few studies have evaluated the analgesic effect of Erector Spinae Plane Block (ESPB) for laparoscopic cholecystectomy surgery. We aimed to evaluate the analgesic effect of ESPB in patients undergoing Laparoscopic Cholecystectomy. METHODS: Seventy-five patients of ASA grade I / II, aged 18-60 years undergoing elective laparoscopic cholecystectomy were enrolled and were randomly assigned to group C or T. Patients in group C were given general anaesthesia alone and patients in group T were given bilateral ultrasound-guided ESPB followed by general anaesthesia. The primary objective was to compare total 24hr postoperative analgesic consumption of tramadol and secondary objective was to indicate the need for rescue analgesia and numeric pain rating scores (NRS) at rest and on movement between the groups. RESULTS: Sixty-six patients were included for final analysis. The total tramadol consumption in 24hr postoperative period for Group T was 105.21 ± 60.18 mg and for group C was 178.12 ± 54.3 mg the difference was statistically highly significant (P = 0.0001). The need for rescue analgesia (fentanyl) was also statistically significantly lower in group T compared to group C (0.91 ± 5.22 mcg vs. 13.64 ± 23.82 mcg, P= 0.002). The postoperative NRS at ½, 2, 4, 6, 8 hr at rest and on movement were statistically lower in group T than group C, although this difference was not of clinical significance. CONCLUSION: In patients undergoing laparoscopic cholecystectomy, bilateral ultrasound-guided ESPB provided effective analgesia as it reduced the total tramadol consumption and the need for rescue analgesia in 24hr postoperative period.

RelB Deficiency in Dendritic Cells Protects from Autoimmune Inflammation Due to Spontaneous Accumulation of Tissue T Regulatory Cells.

Foxp3+ regulatory T cells are well-known immune suppressor cells in various settings. In this study, we provide evidence that knockout of the relB gene in dendritic cells (DCs) of C57BL/6 mice results in a spontaneous and systemic accumulation of Foxp3+ T regulatory T cells (Tregs) partially at the expense of microbiota-reactive Tregs. Deletion of nfkb2 does not fully recapitulate this phenotype, indicating that alternative NF-κB activation via the RelB/p52 complex is not solely responsible for Treg accumulation. Deletion of RelB in DCs further results in an impaired oral tolerance induction and a marked type 2 immune bias among accumulated Foxp3+ Tregs reminiscent of a tissue Treg signature. Tissue Tregs were fully functional, expanded independently of IL-33, and led to an almost complete Treg-dependent protection from experimental autoimmune encephalomyelitis. Thus, we provide clear evidence that RelB-dependent pathways regulate the capacity of DCs to quantitatively and qualitatively impact on Treg biology and constitute an attractive target for treatment of autoimmune diseases but may come at risk for reduced immune tolerance in the intestinal tract.

Blimp1 Prevents Methylation of Foxp3 and Loss of Regulatory T Cell Identity at Sites of Inflammation.

Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. Here, we establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway is dependent on the transcriptional regulator Blimp1, which prevents downregulation of Foxp3 expression and "toxic" gain-of-function of Treg cells in the inflamed CNS. Blimp1 negatively regulates IL-6- and STAT3-dependent Dnmt3a expression and function restraining methylation of Treg cell-specific conserved non-coding sequence 2 (CNS2) in the Foxp3 locus. Consequently, CNS2 is heavily methylated when Blimp1 is ablated, leading to a loss of Foxp3 expression and severe disease. These findings identify a Blimp1-dependent pathway that preserves Treg cell stability in inflamed non-lymphoid tissues.

An Aggressive Large Epithelioid Hemangioendothelioma of the Anterior Mediastinum in a Young Woman.

Hemangioendothelioma is a rare vascular tumor with involvement of the liver, brain, long bones, and lung. Among the 6 histological subtypes, epithelioid hemangioendothelioma (EHE) is the most aggressive. Its occurrence in the mediastinum is quite rare, and very few cases have been documented. The reported cases in the literature have described difficulties in the preoperative diagnosis due to the unusual histological appearance of the tumor. Immunohistochemistry remains the mainstay for a definitive diagnosis. Due to its low incidence, there is no standard treatment for mediastinal EHE, but curative resection is the preferred treatment option where possible, with chemotherapy used as an adjuvant treatment or in cases of widespread inoperable disease. The present case study describes an aggressive EHE occurring in an 18-year-old woman in the anterior mediastinum.

Myeloid-derived suppressor cells control B cell accumulation in the central nervous system during autoimmunity.

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) have been characterized in the context of malignancies. Here we show that PMN-MDSCs can restrain B cell accumulation during central nervous system (CNS) autoimmunity. Ly6G+ cells were recruited to the CNS during experimental autoimmune encephalomyelitis (EAE), interacted with B cells that produced the cytokines GM-CSF and interleukin-6 (IL-6), and acquired properties of PMN-MDSCs in the CNS in a manner dependent on the signal transducer STAT3. Depletion of Ly6G+ cells or dysfunction of Ly6G+ cells through conditional ablation of STAT3 led to the selective accumulation of GM-CSF-producing B cells in the CNS compartment, which in turn promoted an activated microglial phenotype and lack of recovery from EAE. The frequency of CD138+ B cells in the cerebrospinal fluid (CSF) of human subjects with multiple sclerosis was negatively correlated with the frequency of PMN-MDSCs in the CSF. Thus PMN-MDSCs might selectively control the accumulation and cytokine secretion of B cells in the inflamed CNS.

Neurofibromatosis and breast cancer: Do we need to revise the mammographic screening schedule in patients of neurofibromatosis?

Neurofibromatosis type 1 (NF-1) is a neurocutaneous syndrome with autosomal dominant mode of inheritance and has a high propensity to develop benign and malignant nervous system tumors. Although uncommon, case reports describing the association of NF-1 and breast cancer are available in the literature. We illustrate one such case of NF-1, with no family history of the disorder and presenting with multifocal invasive carcinoma of the right breast, in an attempt to describe the association between these two entities. We also attempt to extensively review the current literature on the subject. Since patients with NF-1 are at an increased risk of developing breast cancer, we recommend strict adherence to careful clinical breast examination and annual screening mammographic examination starting at 40 years of age in all patients of NF-1.

Unique properties of thymic antigen-presenting cells promote epigenetic imprinting of alloantigen-specific regulatory T cells.

Regulatory T cells (Tregs) are potential immunotherapeutic candidates to induce transplantation tolerance. However, stability of Tregs still remains contentious and may potentially restrict their clinical use. Recent work suggested that epigenetic imprinting of Foxp3 and other Treg-specific signature genes is crucial for stabilization of immunosuppressive properties of Foxp3+ Tregs, and that these events are initiated already during early stages of thymic Treg development. However, the mechanisms governing this process remain largely unknown. Here we demonstrate that thymic antigen-presenting cells (APCs), including thymic dendritic cells (t-DCs) and medullary thymic epithelial cells (mTECs), can induce a more pronounced demethylation of Foxp3 and other Treg-specific epigenetic signature genes in developing Tregs when compared to splenic DCs (sp-DCs). Transcriptomic profiling of APCs revealed differential expression of secreted factors and costimulatory molecules, however neither addition of conditioned media nor interference with costimulatory signals affected Foxp3 induction by thymic APCs in vitro. Importantly, when tested in vivo both mTEC- and t-DC-generated alloantigen-specific Tregs displayed significantly higher efficacy in prolonging skin allograft acceptance when compared to Tregs generated by sp-DCs. Our results draw attention to unique properties of thymic APCs in initiating commitment towards stable and functional Tregs, a finding that could be highly beneficial in clinical immunotherapy.

Uterine angioleiomyoma: A rare variant of uterine leiomyoma--A case report and literature review.

Uterine angioleiomyoma (AL) is an extremely rare variant of leiomyoma and only 15 cases have been reported till date. Herein we present a case of AL of the uterus in a 39-year-old multiparous female with polymenorrhagia and pain abdomen. A pelvic ultrasonogram showed a large heterogeneously hypoechoic intramural nodule in the posterior myometrium. The patient underwent a total abdominal hysterectomy. Histological examination of the nodule revealed a moderately cellular spindle cell tumor composed of interlacing fascicles of spindle to plump cells swirling around the thick walled vessels. No hypercellularity, pleomorphism, mitotic figures, or necrosis was identified. The spindle to plump cells showed strong and diffuse immunoreactivity for smooth muscle actin, desmin and progesterone receptor, focal and weak positivity for CD10 and estrogen receptor and were negative for CD34 and HMB-45. The Ki-67 labeling index was low (1%). A diagnosis of AL was offered. The patient is on follow up for over 10 months and is asymptomatic.

Incidentally Detected Testicular Metastasis in a Case of Prostatic Adenocarcinoma.

Adenocarcinoma of the prostate is one of the common cancers among elderly men worldwide. However, testicular metastasis detected incidentally after orchiectomy is a rare presentation as most commonly we encounter patients presenting with bone metastasis at the time of primary diagnosis. Here, we describe a recently diagnosed case of prostatic carcinoma that had metastasis in a single testis, incidentally detected in the orchiectomy histopathological specimen, performed for surgical castration and emphasize the importance of routine microscopical examination of the testicular specimens.

Uterine angioleiomyoma: a rare variant of uterine leiomyoma.

Uterine angioleiomyoma is an extremely rare and unique variant of leiomyoma. It usually occurs in middle-aged women, who commonly present with menorrhagia, abdominal pain, or abdominal mass. The lesions are either single or multiple and manifest as submucosal, intramural, or subserosal whorled nodules. Microscopy of the individual nodule shows interlacing fascicles of spindle cells swirling around thick-walled blood vessels. Angioleiomyoma usually lacks mitotic figures, pleomorphism, or necrosis, although cases with marked nuclear atypia and multinucleated giant cells have been reported. The tumor cells are immunoreactive for smooth muscle actin, desmin, h-caldesmon, and progesterone receptor, with a low Ki-67 labeling index. Because these lesions are vascular, they may undergo spontaneous rupture and pose a life-threatening emergency, especially in pregnancy. There are no specific imaging findings; therefore, a preoperative diagnosis is extremely difficult. It is important to recognize this entity and differentiate it from a malignancy, particularly when angioleiomyoma shows significant cytologic atypia or raised cancer antigen 125 levels by thorough sampling. When required, a proper immunohistochemical panel should be used to arrive at a correct diagnosis. In this review, we discuss the current knowledge on uterine angioleiomyoma and its clinical relevance.

Type 1 diabetes-associated IL2RA variation lowers IL-2 signaling and contributes to diminished CD4+CD25+ regulatory T cell function.

Numerous reports have demonstrated that CD4(+)CD25(+) regulatory T cells (Tregs) from individuals with a range of human autoimmune diseases, including type 1 diabetes, are deficient in their ability to control autologous proinflammatory responses when compared with nondiseased, control individuals. Treg dysfunction could be a primary, causal event or may result from perturbations in the immune system during disease development. Polymorphisms in genes associated with Treg function, such as IL2RA, confer a higher risk of autoimmune disease. Although this suggests a primary role for defective Tregs in autoimmunity, a link between IL2RA gene polymorphisms and Treg function has not been examined. We addressed this by examining the impact of an IL2RA haplotype associated with type 1 diabetes on Treg fitness and suppressive function. Studies were conducted using healthy human subjects to avoid any confounding effects of disease. We demonstrated that the presence of an autoimmune disease-associated IL2RA haplotype correlates with diminished IL-2 responsiveness in Ag-experienced CD4(+) T cells, as measured by phosphorylation of STAT5a, and is associated with lower levels of FOXP3 expression by Tregs and a reduction in their ability to suppress proliferation of autologous effector T cells. These data offer a rationale that contributes to the molecular and cellular mechanisms through which polymorphisms in the IL-2RA gene affect immune regulation, and consequently upon susceptibility to autoimmune and inflammatory diseases.

Human regulatory T cells with alloantigen specificity are more potent inhibitors of alloimmune skin graft damage than polyclonal regulatory T cells.

Graft rejection by the immune system is a major cause of transplant failure. Lifelong immunosuppression decreases the incidence of graft rejection; however, nonspecific immunosuppression results in increased susceptibly to infection and cancer. Regulatory T cells (T(regs)), which suppress the activation of the immune system and induce tolerance, are currently under evaluation for use in clinical transplantation. Ex vivo expanded polyclonal T(regs) that are introduced into transplant recipients alter the balance of T effector cells to T(regs); however, experimental data suggest that alloantigen-specific T(regs) would be more effective at preventing graft rejection. We have developed a method to enrich alloantigen-specific human T(regs) based on the coexpression of activation markers, CD69 and CD71. These T(regs) could be readily expanded in vitro and demonstrated potent antigen-specific suppression. In a humanized mouse model of alloimmune-mediated injury of human skin grafts, alloantigen-specific T(regs) resulted in a significant reduction in clinically relevant indicators of dermal tissue injury when compared with polyclonal T(regs), restoring a histology comparable to healthy skin. This method of human allospecific T(reg) selection should be scalable to the clinic. The improved in vivo efficacy of alloantigen-specific T(regs) over polyclonal T(regs) shown here suggests that generating "customized" T(regs) with defined anti-donor allospecificities may improve current practice in clinical immunotherapy.

Effect of nonsurgical periodontal therapy on crevicular fluid levels of Cathepsin K in periodontitis.

OBJECTIVES: Cathepsin K (CTSK), predominantly expressed in osteoclasts, is a potent extracellular matrix degrading enzyme that plays a critical role in osteoclast-mediated bone resorption. Its increased gingival crevicular fluid (GCF) levels in periodontal disease have been reported in a previous study. The present study has been carried out to assess the role of CTSK in periodontal disease and to determine the effect of periodontal treatment on CTSK concentration in GCF. DESIGN: 60 subjects were divided into three groups (n=20) based on gingival index (GI), probing pocket depth (PPD) and clinical attachment loss (CAL): healthy (group I), gingivitis (group II) and chronic periodontitis (group III). A fourth group (group IV) consisted of 20 subjects from group III, 6-8 weeks after nonsurgical periodontal therapy (scaling and root planing). GCF samples collected from each patient were quantified for CTSK using ELISA. RESULTS: The mean CTSK concentration in GCF was found to be the highest in group III, i.e. 55.55 pmol/l. The mean CTSK concentration in GCF in group I and group II was 5.95 pmol/l and 6.90 pmol/l respectively. The mean CTSK concentration in GCF in group IV decreased to 11.15 pmol/l, slightly more than that in groups I and II. CONCLUSIONS: GCF CTSK levels increased in periodontitis and correlated negatively with clinical parameters like GI, PPD and CAL. CTSK levels decreased after nonsurgical treatment of periodontitis. Thus, CTSK can be considered as a 'marker of osteoclastic activity' in periodontal disease and also deserves further consideration as a therapeutic target.

Pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis is a rare cause of respiratory distress in neonates. We present a 4 month old infant who presented with progressive respiratory distress since birth and failure to thrive. He was initially treated as a case of diffuse alveolar disease but on open lung biopsy was diagnosed as pulmonary alveolar proteinosis. The child expired at 7 months of age.

A female with hemihypertrophy and chylous ascites - Klippel-Trenaunay syndrome or Proteus syndrome: a diagnostic dilemma.

Asymmetric overgrowth has many differential diagnoses with considerable overlap, posing a diagnostic dilemma. The presence of chylous ascites, though unreported, might be expected as a manifestation of overgrowth syndromes with lymphatic involvement. We present a patient with hemihypertrophy who presented with chylous ascites at birth.

Haemodynamic instability during transhiatal resection of oesophagus results in postoperative metabolic acidosis and hypoxia: is there a need for assisted ventilation?

Oesophagectomy for oesophageal carcinoma is a stressful physical and metabolic challenge for an individual. The metabolic acidosis and hypoxia resulting postoperatively in a 34-year-old male, suffering from oesophageal carcinoma, after transhiatal oesophagectomy was managed without assisted ventilation contrary to the usual teaching. Relevant literature has been reviewed.