Clinical Profile, Treatment and Outcome of Thrombotic Thrombocytopenia Purpura (TTP) in Rituximab Era- an Experience from Tertiary Care Centre from North India.

Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia (MAHA) resulting from severe deficiency of ADAMTS13. TTP is an acute medical emergency which requires early treatment with therapeutic plasma exchange. With the early use of Rituximab along with PLEX, early response is achieved and relapse rate has gone down. There is lack of published data from India regarding treatment and outcome of TTP. We retrospectively analyzed our data of 21 patients of TTP including 4 patients who had TA-TMA. TTP patients were treated with TPE, pulse methylprednisolone and rituximab. After a median follow up of 57.5 months overall survival in TTP patients was 82.3% in our study and one patient relapsed twice but again responded to same treatment. Relapse free survival was 92.8%. The mortality rate in our study in TTP patients was (3/17) 17.6%. The total response rate was 82.3% (14/17). Out of 4 patients of TA-TMA, Only 33.3% patients responded to plasma exchange in TA-TMA while two patients died (2/4) 50%. Immediate TPE and early rituximab are associated with improved survival in TTP patients, however TA-TMA still remains a significant challenge for transplant physicians and more research is needed in guiding the therapy.

Angiolipoleiomyoma of the Uterus with a Dermoid Cyst in the Right Ovary: An Unusual Association.

Angiolipoleiomyoma is a benign mesenchymal mass composed of smooth muscle, mature adipose tissue, and abnormal blood vessels. It is rarely diagnosed in uterine masses and its prevalence among benign uterine lesions is 0.06%. We report the case of a 40-year-old female presenting with a complaint of heavy menstrual bleeding. Computed tomography scan revealed a large uterine mass with the right ovarian cyst. Histopathological examination confirmed the nature of the lesion as a benign angiolipoleiomyoma with a dermoid cyst of the right ovary. This rare association is reported to apprise gynecologists to consider this unusual tumor during the management of uterine masses.

Improved Outcome of Primary Plasma Cell Leukemia in the Current Era with the Use of Novel Agents and Autologous Bone Marrow Transplants-A Single Centre Experience.

Primary Plasma cell leukemia (pPCL) is an aggressive variant of plasma cell dyscrasias. Diagnostic criteria of plasma cell leukemia were recently updated by international myeloma working group to with more than 5% circulating plasma cells or absolute plasma cell count of more than 500/µL. We performed a retrospective analysis of patients diagnosed with pPCL in our department from 2017 to 2022. Clinical characteristics including the symptoms at presentation, organomegaly, bony involvement and extramedullary involvement were collected. Laboratory parameters including the biochemistry serum protein electrophoresis, serum immunofixation, serum free light chain assay, immunoglobulin profile were sent. Treatment and follow up data was collected. Fifteen patients were diagnosed (8 females and 7 males), median age 59 years (34-70). Six were lost to follow up and nine patients who received treatment at our hospital were analyzed for survival outcome. First line treatment was bortezomib- dexamethasone and immunomodulatory drugs (IMiD). Six (66%) achieved partial response or more and 3 had progressive disease. Five of the nine patients (55%) underwent autologous transplantation. Two out of 5 patients (40%) in the transplant group and 3 of the 4 patients (75%) in the non transplant group have died of the progressive disease. Overall survival was 45% at a median follow up of 14 months. Median OS for patients who underwent auto SCT was 16 months (12-22) versus 10 months (8-12) for patients who did not undergo transplant (Student t test; p value 0.018). Three of the patients achieved MRD negativity after transplant and post transplant consolidation therapy. Survival appears to be improved in patients who respond to initial therapy and are able to achieve MRD negativity which should be the goal of treatment in these patients.

Comparative evaluation of self-pressurized Air-Q® and Proseal™ LMA® in patients undergoing elective surgery under general anaesthesia: A randomized clinical trial.

Background and Aims: Intra-cuff pressure of Air-Q self-pressurized laryngeal airways (Air-Q SP) balances airway pressure and adapts to patient's pharyngeal and periglottic structures, thus improves oropharyngeal leak pressure (OLP).This study was performed to compare efficacy of Air-Q SP with Proseal laryngeal mask airway (PLMA) in patients undergoing elective surgery. Material and Methods: The study design was prospective, randomized and controlled. Ninety patients were randomly assigned to Air-Q SP or PLMA group. All patients were premedicated and shifted to operation theatre. Monitoring was instituted. After securing IV-line, induction with inj. Morphine + Propofol, relaxation with inj. Vecuronium was done. Supraglottic was inserted according to group allocation. Outcome measures were OLP, fibreoptic view of larynx, success rate, device insertion parameters, haemodynamic and respiratory parameters and post-operative laryngopharyngeal complications. Neostigmine + glycopyrrolate were given, device was extubated. Results: All supraglottic airway devices (SADs) were successfully placed in two attempts. The mean initial OLP, OLP at 10 minutes, and device insertion time were significantly lower in Air-Q SP group. Fiber-optic laryngeal view grading was significantly better with Air-Q SP. No significant difference was observed with respect to rate of successful insertion in first attempt, ease of insertion, and manipulations required. The hemodynamic/respiratory parameters and post-operative sore throat in the two both groups were similar. Conclusions: Proseal LMA has a higher OLP than Air-Q SP but average insertion time was better, and fiber-optic grading of laryngeal view was shorter with Air-Q SP. However, Air-Q SP and Proseal LMA were both effective for lung ventilation.

Comparison of the analgesic efficacy of two different fascial blocks in patients undergoing laparoscopic inguinal hernia surgery: A randomized control trial.

Background and Aims: Moderate-to-severe intensity pain is reported on the first day following lower abdominal surgery. No study has compared transversus abdominis plane (TAP) block with retrolaminar block (RLB) in laparoscopic inguinal hernia surgery for postoperative pain relief. Material and Methods: In this prospective, randomized trial, 42 male patients of American Society of Anesthesiologists (ASA) physical status I and II, aged 18-65 years, and having a BMI <40 kg/m2 received TAP or RLB following laparoscopic inguinal hernia surgery. A standard general anesthetic technique was performed. Patients were randomized into two groups: single-shot TAP block (group I) (n = 21) or the RLB (group II) (n = 21) with bilateral 20 ml of 0.375% ropivacaine. Postoperatively, IV paracetamol 1 g was administered as rescue analgesia. Postoperative cumulative Visual Analogue Scale (VAS) score 24 hours after surgery was considered as the primary outcome. Results: Postoperative cumulative VAS score at rest at 24 h, represented as mean ± S.D (95% CI), in the TAP block group was 3.54 ± 3.04 (2.16-4.93) and in the RLB group was 6.09 ± 4.83 (3.89-8.29). P value was 0.112 and VAS on movement was 7.95 ± 3.41 (6.39-9.50 [2.5-15.0]) in TAP block group, whereas P value was 0.110 and VAS on movement was 10.83 ± 5.51 (8.32-13.34) in the RLB group. Conclusion: Similar postoperative cumulative pain score on movement at 24 h was present in patients receiving TAP block or RLB. However, VAS score at rest and on movement was reduced in patients receiving TAP block at 18 and 24 h postoperatively.

Assessment of the phenotypic severity of hemophilia A: using rotational thromboelastometry (ROTEM) and APTT-clot waveform analysis.

BACKGROUND: Hemophilia A (HA) is an X-linked inherited bleeding disorder caused by reduced factor VIII (FVIII) levels. Approximately 10-15% of patients with severe HA (SHA) do not present with the anticipated bleeding pattern. Here, we assessed the phenotypic severity of hemophilia A using rotational thromboelastometry (ROTEM) and activated partial thromboplastin time-clot waveform analysis (APTT-CWA). METHODS: Patients diagnosed with hemophilia A were enrolled. Clinical phenotype assignment was performed according to the published literature, and patients were classified into four phenotypic subgroups. The whole blood sample was first run on ROTEM in INTEM mode using platelet-poor plasma, APTT was run, and the APTT-CWA graph was simultaneously recorded. RESULTS: A total of 66 patients were recruited for this study. Statistically significant differences were observed between the four phenotypically categorized groups using ROTEM and APTT-CWA. On comparing patients with mild/moderate-to-severe phenotypes (Group II) with SHA without inhibitors (Group IV), no significant difference was found for all parameters of ROTEM or APTT-CWA. The MCF, MA30, MAXV, and Alpha angle values using ROTEM were found to be the lowest in patients with SHA with inhibitors, which helped differentiate them from those with SHA without inhibitors. However, these two groups could not be differentiated using the APTT-CWA parameters. CONCLUSION: ROTEM can be used to distinguish patients with SHA with inhibitors from those with SHA without inhibitors using a combination of parameters with high sensitivity and specificity. However, APTT-CWA cannot be used to differentiate these patient groups.

Acute panmylelosis with myelofibrosis - A rare case report with review of literature.

ABSTRACT: Acute panmyelosis with myelofibrosis (APMF) corresponds to <1% cases of acute myeloid leukemia, which could be an underestimation due to missed diagnosis. Due to its rapidly fatal course, it warrants a timely and correct diagnosis. We present a case of a 44-year male who came with a short history of fever, generalised weakness, revealed pancytopenia with occasional circulating blast in the peripheral blood smear. Bone marrow aspirate was dry tap,biopsy revealed panmyelosis with myelofibrosis with increased (22%) blasts. Flowcytometric immunophenotyping, cytogenetics and molecular tests were undertaken. Together with clinical details, immunophenotypic profile, cytogenetics and molecular studies, the diagnosis of Acute panmyelosis with myelofibrosis was made and managed accordingly. 32 The WHO 2017 describes APMF as an acute panmyeloid proliferation with increased blasts (≥20% in the bone marrow or peripheral blood) and accompanying marrow fibrosis. APMF is rare with poor prognosis thus, must be differentiated especially from Acute megakaryoblastic leukemia to arrive at the correct diagnosis which will help reduce/prevent the early mortality by providing timely chemotherapy followed by upfront hemopoietic stem cell transplantation.

Case of angioimmunoblastic T-cell lymphoma presenting as peripheral and bone marrow plasmacytosis: A diagnostic conundrum.

ABSTRACT: Angioimmunoblastic T-cell lymphoma (AITL), a subtype of peripheral T-cell lymphoma (PTCL), is associated with unique clinical, morphological, and immunohistochemical features. The peripheral circulation might show presence of an occasional reactive plasma cell but significant plasmacytosis masquerading as plasma cell leukemia is rare. We report a case of AITL in a 42-year-old male, who presented with two-month history of generalized lymphadenopathy. On investigations, he had hypergammaglobulinemia and plasmacytosis in the peripheral blood and bone marrow masquerading as plasma cell leukemia. Immunohistochemistry and serum protein electrophoresis revealed polyclonal nature of plasma cells. Diagnosis of AITL was made on cervical lymph node biopsy. This case highlights the diagnostic challenge faced due to heterogeneity in the clinical presentation and pathological findings and to alert the clinician so that timely accurate diagnosis can be made to initiate the treatment.

Pelvic Synovial Sarcoma Clinically Masquerading as an Ovarian Malignancy.

Background: Synovial sarcoma, a malignant mesenchymal tumor, commonly involves the extremities and is rarely found in the pelvis. Cytology with a biphasic pattern can suggest the diagnosis of synovial sarcoma. Case Report: A 32-year-old female presented with complaints of abdominal distension. She was initially evaluated in another hospital where she underwent ultrasound-guided fine needle aspiration cytology (FNAC) of the abdominal mass. The mass was diagnosed as ovarian adenocarcinoma, and the patient underwent 3 cycles of chemotherapy. After 3 months, she was referred to our institute for surgical excision of the mass. Contrast-enhanced computed tomography of the abdomen suggested a well-circumscribed, heterogeneous, solid-cystic mass in the left adnexal region measuring 13.9 × 10 × 9.1 cm and compressing the adjacent structures. No previous radiologic investigations were available. We reviewed the FNAC slide from the outside hospital and made a preliminary diagnosis of biphasic synovial sarcoma. The patient underwent debulking surgery consisting of panhysterectomy with excision of the pelvic mass. Microscopic examination of the pelvic mass showed a biphasic tumor composed of epithelial and mesenchymal components, suggestive of synovial sarcoma. The immunohistochemistry profile supported the morphologic diagnosis. Bilateral ovaries were unremarkable. The patient received 4 cycles of adjuvant chemotherapy and is presently asymptomatic. Conclusion: Although primary pelvic synovial sarcoma is a rare occurrence, this case illustrates that synovial sarcoma can be diagnosed or at least suspected on FNAC. Because of the importance of adjuvant chemotherapy, synovial sarcoma must be high on the list of differential diagnoses of high-grade intra-abdominal masses.

Stimuli-Responsive Self-Assembly Disassembly in Peptide Amphiphiles to Endow Block-co-Fibers and Tunable Piezoelectric Response.

Supramolecular assemblies with well-defined structural attenuation toward varied functional implications are an emerging area in mimicking natural biomaterials. In that regard, the redox stimuli-responsive ferrocene moiety can reversibly change between a nonpolar ferrocenyl and polar ferrocenium cation that endows interesting modular features to the building blocks with respect to self-assembly/disassembly. We design a series of ferrocene anchored peptide fragment NVFFAKKC using hydrophobic alkyl spacers of different chain lengths. Increasing the spacer length between the redox-responsive and self-assembling motifs increases the propensity to form robust nanofibers, which can be physically cross-linked to form hydrogels. The controlled redox response of the ferrocene moiety tandem with pH control provides access to structural control over the peptide nanostructures and tunable mechanical strengths. Further, such redox-sequestered dormant states hinder the spontaneous nucleation process that we exploit toward seeded supramolecular polymerization to form block cofibers composed of redox-responsive periphery and nonresponsive cores. Finally, such redox sequestration of peptide self-assembly renders an on-off piezoelectric response for potential utilization in peptide bioelectronics.

The efficacy of ultrasound-guided triple nerve block (ilioinguinal, iliohypogastric, and genitofemoral) versus unilateral subarachnoid block for inguinal hernia surgery in adults: a randomized controlled trial.

INTRODUCTION: The present study was carried out to evaluate the efficacy of ultrasound-guided triple nerve block (ilioinguinal, iliohypogastric, and genitofemoral) versus unilateral subarachnoid block for adult male patients undergoing unilateral inguinal hernia surgery. MATERIAL AND METHODS: Sixty ASA I-III adult male patients > 18 years old, scheduled for unilateral inguinal hernia surgery were randomly allocated into 2 groups of 30 patients each. In Group A ( n = 30) the patients received ultrasound-guided nerve block (ilioinguinal, iliohypogastric, and genitofemoral), and in Group B ( n = 30) the patients received unilateral subarachnoid block. The primary outcome was to assess postoperative analgesic efficacy (visual analogue scale [VAS] scores at rest and during coughing/ambulation). The secondary outcomes were time to first rescue analgesia with morphine, the total dose of morphine used as rescue analgesia, urinary retention, time to first micturition, time to first unassisted walking, and time to discharge from the surgical recovery room. RESULTS: The mean pain scores at 1, 2, 4, and 6 hours during rest and during coughing/ambulation were significantly lower in Group A when compared to patients in Group B ( P < 0.001). There was no requirement for rescue analgesic opioids in Group A ( P < 0.001). Mean time to first micturition and mobilization occurred earlier in Group A, leading to early discharge from the recovery room ( P < 0.001). No major side effects were observed in any of the study groups. CONCLUSIONS: Ultrasound-guided triple nerve block technique can be used as a sole anaesthetic technique for inguinal hernia surgery because it not only provides optimal anaesthesia intra-operatively but also has a favourable analgesic and opioid-sparing efficacy in the early postoperative period with minimal adverse effects.

Transcriptomic Profiling Unravels Novel Deregulated Gene Signatures Associated with Acute Myocardial Infarction: A Bioinformatics Approach.

Acute myocardial infarction (AMI) is a severe disease with elevated morbidity and mortality rate worldwide. This is attributed to great losses of cardiomyocytes, which can trigger the alteration of gene expression patterns. Although several attempts have been made to assess the AMI biomarkers, to date their role in rescuing myocardial injury remains unclear. Therefore, the current study investigated three independent microarray-based gene expression datasets from AMI patients (n = 85) and their age-sex-matched healthy controls (n = 70), to identify novel gene signatures that might be involved in cardioprotection. The differentially expressed genes (DEGs) were analyzed using 'GEO2R', and weighted gene correlation network analysis (WGCNA) was performed to identify biomarkers/modules. We found 91 DEGs, of which the number of upregulated and downregulated genes were 22 and 5, respectively. Specifically, we found that the deregulated genes such as ADOR-A3, BMP6, VPS8, and GPx3, may be associated with AMI. WGCNA revealed four highly preserved modules among all datasets. The 'Enrichr' unveiled the presence of miR-660 and STAT1, which is known to affect AMI severity. Conclusively, these genes and miRNA might play a crucial role the rescue of cardiomyocytes from severe damage, which could be helpful in developing appropriate therapeutic strategies for the management of AMI.

Anion-responsive self-assembled hydrogels of a phenylalanine-TREN conjugate allow sequential release of propranolol and doxorubicin.

Stimuli-responsive self-assembled and supramolecular hydrogels derived from peptide amphiphiles have opened exciting new avenues in biomedicine and drug delivery. Herein, we screened a series of phenylalanine-amphiphiles possessing polyamine and oxyethylene appendages for their self-assembly and anion-responsiveness and found that the tris(aminoethyl)amine (TREN) containing amphiphile NapF-TREN formed injectable hydrogels that could be disrupted upon the addition of stoichiometric amounts of tetrahedral monovalent anions such as H2PO4- and HSO4-, while the addition of other anions such as Cl-, HPO42-, CO32-, HCO3- or SO42- did not affect the gel stability. The anion-gelator interaction was investigated by 1H and 31P NMR spectroscopy as well as by Isothermal Titration Calorimetry (ITC). These studies confirmed a 1 : 1 stoichiometry and revealed negative enthalpy and negative entropy for the binding of H2PO4- with NapF-TREN. Microscopic investigations by TEM, AFM, and SAXS revealed that H2PO4- anions induced a nanofiber-to-nanoglobule morphological change in the aqueous self-assemblies of NapF-TREN. However, upon ageing the samples, slow reformation of the nanofibers was also observed, reflecting the reversibility of the anion-gelator interaction. The anion- and pH-responsive nature of the NapF-TREN hydrogels was exploited to program sequential release of entrapped drugs propranolol and doxorubicin.

Multiple tuberous xanthomas diagnosed on fine-needle aspiration cytology - Report of a rare case.

Xanthomas are papulonodular skin lesions present in lipoprotein metabolism disorders, which result in cholesterol deposits in subcutaneous tissue, tendons, ligaments, periosteum, etc. A 28-year-old male presented with multiple soft-tissue swellings, prominently over joints. Fine-needle aspiration (FNA) from multiple sites had similar appearance with foamy histocytes and giant cells. We describe an unusual case of tendinous and tuberous xanthoma diagnosed by cytology. Acquaintance with FNA cytology findings in xanthomas can help to avoid the need of surgical biopsy, as xanthomas can regress on medical therapy alone.

COVID-19, Mucormycosis and Cancer: The Triple Threat-Hypothesis or Reality?

COVID-19 has been responsible for widespread morbidity and mortality worldwide. Invasive mucormycosis has death rates scaling 80%. India, one of the countries hit worst by the pandemic, is also a hotbed with the highest death rates for mucormycosis. Cancer, a ubiquitously present menace, also contributes to higher case fatality rates. All three entities studied here are individual, massive healthcare threats. The danger of one disease predisposing to the other, the poor performance status of patients with all three diseases, the impact of therapeutics for one disease on the pathology and therapy of the others all warrant physicians having a better understanding of the interplay. This is imperative so as to effectively establish control over the individual patient and population health. It is important to understand the interactions to effectively manage all three entities together to reduce overall morbidity. In this review article, we search for an inter-relationship between the COVID-19 pandemic, emerging mucormycosis, and the global giant, cancer.