Immunophenotypic Profile and Measurable Residual Disease Monitoring in Multiple Myeloma: A Prospective Study From a Tertiary Care Centre in Southern India.

BACKGROUND: Multiple myeloma (MM) immunophenotyping (IPT) and measurable residual disease (MRD) monitoring by flow cytometry is a surrogate for progression-free survival and overall survival in clinical trials. However, plasma cell enumeration is challenging owing to morphological discrepancies and plasma cell (PC) loss during the sample processing. METHODS: In (n=87) newly diagnosed MM patients, we evaluated the immunophenotype of PCs at baseline, and for a subset of 35 patients MRD at post-induction was quantified and analyzed for association with outcomes and survival. The software Statistical Package for Social Sciences (SPSS), version 16.0 (SPSS Inc., Chicago, IL, USA) was used for all the statistical analysis. RESULTS: Immunophenotyping showed strong positive expression of CD56 (83%), CD200 (94%), CD38 (92%), and CD117 (91%) and negative/weak expression of CD19 (83%), CD45 (89%), CD27 (74%), and CD81 (90%) respectively. Negative/weak expression of CD19 was significantly associated with age ≥56 years (p<0.048), with lower albumin (<3.4g/dL, p<0.001). Strong positive CD56 expression was significantly associated with the presence of M-protein (p<0.03). Strong positive CD117 expression was significantly associated with lower albumin (p<0.02). Strong positive CD200 expression was significantly associated with a good response (p<0.02). The median (IQR) value of bone marrow (BM)-MRD% was 0.005 (0.002-0.034). We found that there was no significant difference in the correlation, association, and survival outcomes with MRD%. CONCLUSION: This study sheds light on the utility of IPT as an invaluable diagnostic tool in disease management. The findings of this study could be important when it comes to modifying the criteria for high-risk diseases and implementing a risk-adapted first therapy in clinical practice.

Prevalence of Selected Cardiovascular Risk Factors and Their Associated Factors among People Living with HIV/AIDS in India.

Background: Low- and middle-income countries face the dual problem of infectious and non-infectious diseases. Persons living with HIV/AIDS (PLHIV) are also at risk of cardiovascular diseases. Hence, we did this study to determine the prevalence of cardiovascular risk factors (CVRF) among PLHIV and to find the factors associated with it. Methods: We carried out a cross-sectional analytical study among all adults aged ≥18 years registered at a facility-integrated anti-retroviral therapy center in Puducherry, India, from September 2016 to February 2018. After obtaining informed consent, we interviewed the participants to assess physical activity, alcohol, and tobacco use. We measured weight, height, abdominal circumference, and blood pressure, with biochemical investigations such as blood glucose and lipid profile. Results: Of the total 316 adults PLHIV studied, the most common cardiovascular risk factor found was dyslipidemia (82.7%), followed by inadequate physical activity (74.4%). Other behavioral risk factors studied, such as current tobacco use and current alcohol use, showed a prevalence of 12.8% and 5.4%, respectively, among male participants. The prevalence of hypertension among adult PLHIV studied was 15.8%, and diabetes was 12.3%. In the multivariate analysis, diabetes, and hypertension were significantly associated with age and literacy. Obesity was found to be associated with diabetes and abdominal obesity with dyslipidemia. Conclusion: Dyslipidemia was the most common cardiovascular risk factor, followed by inadequate physical inactivity among PLHIV. Regular screening with blood glucose, blood pressure, and lipid profile, and timely cross-referrals can help in the early detection of CVRF among PLHIV and hence improve their quality of life through appropriate treatment.

Impact of Genetic Polymorphisms in NF-ĸB2 and TRAF3 Genes on Response to Bortezomib-Based Therapy in Multiple Myeloma Patients.

BACKGROUND: Multiple myeloma (MM), being the second most common hematological malignancy, has garnered significant attention. The ubiquitin proteasomal pathway (UPP), crucial for normal cell function, plays a pivotal role in myeloma pathophysiology, especially with the advent of bortezomib (BTZ). Dysregulation of the UPP has implications ranging from developmental abnormalities to cancer. OBJECTIVES: This study aimed to delineate the clinical characteristics of newly diagnosed multiple myeloma patients and investigate the influence of single nucleotide polymorphisms (SNPs) in NF-ĸB2 and TRAF3 genes on the risk and treatment response to bortezomib-based chemotherapy. MATERIALS AND METHODS: Conducted at JIPMER, Pondicherry, this prospective study enrolled 184 participants, comprising cases and controls. DNA extraction from peripheral blood samples was followed by SNP analysis through Real-time Polymerase Chain Reaction. Patients were categorized into Good and Poor responders, and SNP associations with treatment response, response rates, and survival outcomes were assessed using chi-square and Kaplan-Meier analyses. RESULTS: The median age of participants was 55 years, with backache being the most prevalent symptom (66.3%). Hypercalcemia (22%), renal failure (8.7%), and bone fractures (45.7%) were also observed, alongside high prevalence of anemia. Notably, the frequency of the TRAF3 rs12147254 A allele was lower in cases compared to controls (31% vs. 49%, P-value=0.002). Poor responders exhibited higher frequencies of the GA+AA genotypes in TRAF3 rs12147254 (OR-3.882(1.629-9.251), P-value-0.002) and NFKB2 rs1056890 (OR-3.308(1.366-8.012), P-value-0.008) when compared to good responders. The GA+AA genotype in TRAF3 rs11160707 SNP correlated with improved progression-free survival. CONCLUSION: The study findings underscore a significant association between genetic polymorphisms and treatment response outcomes, suggesting their utility in prognostic determinations and clinical outcomes prediction in multiple myeloma patients.

Quantification of circulating clonal plasma cells by multiparametric flow cytometry as a prognostic marker in patients with newly diagnosed multiple myeloma.

BACKGROUND: Studies have shown that the quantification of circulating clonal plasma cells (cCPCs) in peripheral blood using flow cytometry could be used as a prognostic predictor of poor outcome in multiple myeloma (MM). METHODS: In 66 newly diagnosed MM, cCPCs were quantified (cCPC%) and analysed for association with outcome and survival. Single-tube combined surface (CD45/CD19/CD138/CD38/CD56/CD27/CD81 as per availability) and cytoplasmic (kappa/lambda) staining was done using pre-titrated volumes of antibodies. In 26 patients, repeat cCPC% was assessed post-induction therapy. For association studies, treatment response has been taken as good (VGPR and above) and poor (PR and below). All statistical analyses were performed with SPSS software version 16.0. RESULTS: There was no significant association between cCPC% at baseline with staging (p = 0.43), ß2 -microglobulin (p = 0.27) and albumin (p = 0.08). There was a significant difference between the pre-induction and post-induction cCPC% (p = 0.0001). The patients were segregated using a cut-off of ≥0.197 and <0.197 based on the median values of baseline cCPC%. The post-induction outcome was available for 47 patients among whom 33 (70%) had VGPR and above. There was a significant association between higher cCPC% at baseline with poor treatment response (p = 0.008). The median OS in the study patients was 42 (CI 28.14-43.03) months and the median PFS was 39 (CI 28.49-49.04) months. Higher cCPC% showed a lower median PFS (30 vs. 39 months) and OS (35 vs. 41 months) compared to lower cCPC% though it was not statistically significant. CONCLUSION: Flow cytometric baseline cCPC% in newly diagnosed MM was associated with poor treatment response and survival.

Supplementation of Water-Soluble Vitamins Reduces Hyperhomocysteinemia, Insulin Resistance, and High-Sensitivity C-reactive Protein in Prehypertension Subjects.

BACKGROUND: Prehypertensives are at higher risk of developing cardiovascular diseases. Hyperhomocysteinemia, insulin resistance, and increased high-sensitivity C-reactive protein (hs-CRP) are independent risk factors for the development of cardiovascular complications. In prehypertensives, specific therapeutic approaches can be implemented at the earliest to prevent the onset of overt hypertension. So the present study was performed to study the effect of supplementation of water-soluble vitamins on cardiovascular risk factors like homocysteine, insulin resistance, and C-reactive protein in prehypertensive subjects. METHODS: Sixty prehypertensive subjects were recruited into the study based on inclusion and exclusion criteria and randomized into two groups of 30 each. One group was given a placebo and the other was given water-soluble vitamins for four months. Serum homocysteine, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and hs-CRP were assayed. RESULTS: After four months of treatment with water-soluble vitamins, there was a significant decrease in levels of serum homocysteine, hs-CRP, and HOMA-IR when compared to placebo treatment. After four months of treatment, there was a significant decrease in the levels of hs-CRP, homocysteine, and HOMA-IR in groups treated with water-soluble vitamins compared to the basal levels. CONCLUSION: In subjects with prehypertension, supplementation of water-soluble vitamins decreases the level of homocysteine, insulin resistance, and hs-CRP.

Bacteriuria due to Typhoidal and Nontyphoidal Salmonella: A Report of Three Cases from South India.

Urinary tract infection (UTI) with Salmonella is uncommon, accounting for merely 0.01% to 0.1% of cases of UTIs. It is reported more frequently in the presence of predisposing factors such as structural abnormalities of the urinary tract or weakened immune system. We present a case series of three patients with Salmonella bacteriuria and their susceptibility patterns. All three patients had underlying urologic features such as neurogenic bladder, chronic kidney disease, and urethral stricture, and two presented with urinary tract involvement symptoms.

Assessment of Plasmodium falciparum histidine rich protein 2 and /3 (pfhrp 2&/ pfhrp 3) gene deletion or mutation in Plasmodium falciparum positive blood samples in a tertiary care centre in South India.

Rapid diagnostic card tests (RDTs) enable timely and appropriate diagnosis of malaria especially in remote areas. Plasmodium falciparum histidine rich protein 2 (PFHRP2) is the most targeted antigen for the detection of Plasmodium falciparum infections by rapid diagnostic card test. Genetic mutations and gene deletions are important emerging factors for false-negative RDTs, which may delay the provision of life-saving treatment for the patients. Hence, we would like to evaluate for the existence of pfhrp2/3 gene deleted P. falciparum parasites in our health care setting. This study was conducted for a period of 2 years in a tertiary care centre in South India. Blood samples that are microscopically confirmed as P. falciparum but negative by RDT were assessed for the presence of pfhrp2, pfhrp3, and their flanking genes using conventional PCR. Follow up of the clinical outcomes were also done for these patients. Of the 63 positive samples collected (50 /63) 79.4% were P.vivax and (13/63) 20.6% were P.falciparum by PCR. Among the 13 P. falciparum positive samples, 4 samples (4/13), (95% CI -10.36% to 61.11%) were found to be RDT negative but microscopically positive.Pfhrp2,pfhrp3 and their flanking genes were amplified for these 4 samples. All 4 samples were found to be negative for both pfhrp2-2 & pfhrp2-3 exon regions and also varying patterns of flanking gene deletions were also noted.This study provides molecular evidence for the existence of pfhrp2 & pfhrp3 deleted P. falciparum parasites in a tertiary care centre in South India warranting periodic evaluation of pfhrp2 based RDT use. Only pfhrp2/3 RDT based decision on diagnosis of P.falciparum malaria should always be reconsidered especially in remote areas.

Prevalence of Oral Lesions and Its Associated Risk Factors Among PLHIV Availing Anti-Retroviral Therapy from a Selected Tertiary Care Hospital, Puducherry - A Cross Sectional Analytical Study.

Background and Objectives: Oral lesions are among the earliest and most important indicators of infection with human immunodeficiency virus (HIV). The presence of oral lesions has a significant impact on the physical and mental health of the PLHIV. Hence, a novel attempt is made to assess the prevalence of various types of oral lesions among the adult people living with human immunodeficiency virus (PLHIV) undergoing antiretroviral therapy. Methodology: In this facility-based cross-sectional study, a total of 239 out of 300 eligible PLHIV were assessed between September and October 2018. All consecutive eligible patients encountered during the data collection period were included. Oral examination was carried out using disposable mouth mirrors, sterile piece of cotton, and bright illuminated torch. Results: The prevalence of oral mucosal abnormalities was found to be 25% (95% confidence interval: 20.03-30.97). The most prevalent oral lesions were acute necrotizing ulcerative gingivitis, acute necrotizing ulcerative periodontitis, and candidiasis. CD4 count <200 cells/mm3, current tobacco use, and alcohol usage were significantly associated with the prevalence of oral lesions. Conclusion and Recommendations: The study revealed that one-fourth of the study participants had oral lesions. Strategies for early detection and prompt treatment of oral lesions need to be planned and incorporated in the program to reduce the morbidity due to oral lesions.

A Common Neurological Presentation With an Unusual Etiology: Dense Hemiplegia Due to Pneumococcal Meningitis.

Acute hemiplegia is a common neurological presentation that usually occurs due to a cerebrovascular accident. A similar presentation may also be seen in several other conditions such as postictal (Todd's) paralysis, hemiplegic migraine, brain abscess, and extradural or subdural hemorrhage. We present the case of a 32-year-old South Indian female who was brought to the emergency department with acute hemiplegia and decreased responsiveness for one day. She was provisionally diagnosed with an ischemic stroke at presentation; however, contrast-enhanced computed tomography (CECT) of the brain with CT angiography and venography revealed no focal lesions or filling defects. CSF examination showed gram-positive cocci in pairs, concerning brain abscess. Magnetic resonance imaging (MRI) of the brain was suggestive of multiple evolving abscesses in the right frontal and parietal lobes. Her hemiplegia was attributed to the abscess, and she was given six weeks of intravenous (IV) antibiotics, after which she recovered completely. Maintaining a high index of clinical suspicion enabled the correct diagnosis in a patient who did not have any typical features of acute meningitis.

Hypervirulent Klebsiella pneumoniae infection presenting as endocarditis and liver abscess.

Hypervirulent Klebsiella pneumoniae infection, reported commonly from South-east Asia, is predominantly community-acquired and affects young healthy adults. Although abscesses of liver, brain and muscles, endophthalmitis or osteomyelitis have been reported, Infective endocarditis is a rare manifestation. This report illustrates a patient with uncontrolled diabetes mellitus who presented with clinical features of liver abscess with an incidental finding of infective endocarditis. Hypervirulent K. pneumoniae, which was isolated from blood culture of the patient carried the plasmid borne key virulence markers-rmpA and rmpA2 with enterobactin (entB), type 3 fimbriae (mrkD) and was of K1 type and ST3321, an uncommon clone of Hypervirulent K. pneumoniae. Transthoracic Echocardiography showed multiple mobile vegetations attached to mitral valve and posterior wall of left ventricle. With appropriate antibiotics blood cultures turned sterile, liver abscess and cardiac vegetations reduced in size. Mitral Valve replacement surgery was proposed. He declined treatment and succumbed to the infection subsequently.

Effectiveness of low-volume split-dose versus same-day morning polyethylene glycol regimen for adequacy of bowel preparation in patients undergoing colonoscopy: A single-blinded randomized controlled trial.

BACKGROUND: Successful completion of colonoscopy depends largely on the quality of bowel preparation. Polyethylene glycol (PEG) is a commonly used preparation for colonoscopy. The timing of bowel preparation has evolved from previous day evening to the currently recommended split-dose regimen. It was observed that consumption of entire or a portion of PEG on the previous day can interfere with work and sleep. Hence, we designed this single-blinded randomized controlled trial (RCT) to evaluate the efficacy, tolerability, and acceptability of the same-day PEG as compared with lowvolume split-dose PEG in patients undergoing late morning colonoscopy. METHODS: A total of 384 patients were randomized to same-day (SD group; n = 192) and split-dose (SPL group; n = 192) bowel preparation. The patients in both the groups received bisacodyl 10 mg at bedtime on the day prior to colonoscopy. The patients in the SD group took 2 L of PEG between 5:00 AM and 7:00 AM on the day of colonoscopy. The SPL group took 1 L of PEG between 6:00 PM and 7:00 PM on the preceding day and another liter between 6:00 AM and 7:00 AM on the day of colonoscopy. The adequacy of bowel preparation was assessed using the Boston Bowel Preparation Scale (BBPS). Tolerability was scored by recording symptoms such as nausea, vomiting, bloating, and abdominal pain. Acceptability was based on the overall satisfaction, willingness to repeat the same preparation, and interference with sleep on the preceding night. RESULTS: The median (interquartile range, [IQR]) BBPS in the SD group was 8 (6-9) while that in the SPL group was 6 (5-8) and this difference was statistically significant (p < 0.001). Similarly, a significantly higher proportion of patients in the SD group (86%) achieved adequate bowel preparation (BBPS score ≥ 6) when compared to those in the SPL group (73.4%) (p = 0.002). Tolerability as assessed by nausea, vomiting, bloating, and abdominal pain was similar in both the groups. There was also no significant difference with respect to overall satisfaction of taking bowel preparation (p = 0.33) or willingness to repeat the same regimen (p = 0.37) between the two groups. Patients in the SPL group had more interference with sleep on the preceding night (54% vs. 14.5%, p < 0.001). CONCLUSION: Same-day morning PEG regimen can be considered an effective, well-tolerated, and acceptable bowel preparation for colonoscopy.

De Novo Crohn's Disease Triggered After COVID-19: Is COVID-19 More Than an Infectious Disease?

Coronavirus disease 2019 (COVID-19)-associated immune dysregulation is believed to trigger the onset of various autoimmune diseases. These occur either during active COVID-19 or soon after recovery. We report ileocolonic Crohn's disease in a 35-year-old woman after her recovery from a milder form of COVID-19. She achieved remission of her symptoms with oral corticosteroids and sulfasalazine.

Guillain-Barré Syndrome Following Chickenpox With Multiple Cranial Nerve Palsies and Cerebrospinal Fluid Pleocytosis.

Guillain-Barré syndrome (GBS) is a rare complication of chickenpox. All cases of post-varicella GBS published in the literature have been associated with the classical albuminocytological dissociation. We report the case of a 48-year-old male with flaccid areflexic quadriparesis and bilateral seventh, ninth, tenth, and twelfth cranial nerve palsies 10 days after chickenpox. Cerebrospinal fluid (CSF) analysis done in the second week showed marked lymphocytic pleocytosis. Electroneurographic studies were suggestive of acute inflammatory demyelinating polyradiculopathy. He had near-total neurological recovery with intravenous immunoglobulin. Our case demonstrates that GBS can occur after primary varicella infection, and marked CSF pleocytosis can be an additional feature.

Neurological recovery with serological response in a rabies survivor on long-term follow-up.

An 18-year-old girl presented with headache, vomiting, dysarthria, diplopia and ataxia following a stray dog bite 20 days prior to presentation. The dog was killed by her neighbours. She received three doses of anti-rabies vaccine and one dose of rabies immunoglobulin (RVIG) before presentation. Diagnosis of rabies was confirmed based on four-fold rise in serum and CSF rabies virus neutralizing antibodies (RVNA) by rapid fluorescent focus inhibition test (RFFIT) titres coupled with history of dog-bite and a normal MRI. With supportive care and empirical administration of IVIG her condition improved over months and at her final visit to hospital at five years, she was physically independent with mild persistent dysarthria. Ours is one of the longest followed cases of rabies survivor in whom we had used IVIG empirically and could demonstrate the decline in the RVNA level in CSF and verify the steady neurological recovery over five years.

Willingness and yield of screening for hepatitis B among outpatients of a tertiary care centre, Puducherry, South India.

India's National Viral Hepatitis Control Programme recommends screening outpatients for hepatitis B at tertiary care centres. We aimed to assess the yield of screening and reasons for refusal for testing. We included adult outpatients at a tertiary care centre, South India during September and October 2019. Participants' willingness to be tested and the reasons for refusal were noted. Fingerstick blood sample was tested for HBsAg using rapid kit. Of a total of 700 participants, 157 (22%, 95% CI: 19.4-25.7%) were unwilling to be tested. Men were more unwilling (26%) compared to women (19%) (aPR 1.90 95% CI: 1.22-2.94; p = 0.004). 'Lack of time' was the most common reason reported for refusal (10%). Of 543 participants tested, 15 (2.8%, 95% CI: 1.6-4.5%) were positive for HBsAg. Similar studies from other regions in India are required for the estimation of yield of opportunistic approach.

Sister Mary Joseph Nodule as an Initial Presentation of Pancreatic Adenocarcinoma.

Sister Mary Joseph (SMJ) nodule is a metastatic umbilical nodule seen in primary tumors of the gastrointestinal or genitourinary tract. The stomach and colon are the common gastrointestinal cancers associated with SMJ nodule. The pancreas is a rare primary site for umbilical metastasis. Moreover, malignant umbilical nodules as the first presentation in pancreatic cancer is rare. Pancreatic adenocarcinoma that metastasizes to umbilicus usually arise from the body or tail of the pancreas. The presence of SMJ nodule usually indicates poor prognosis. Umbilical nodule is a simple physical finding to the presence of an advanced intra-abdominal malignancy. Although rare, pancreatic cancer should be considered as one of the primary sites in such a situation.

Histopathological Profile In Fatal Yellow Phosphorous Poisoning.

Yellow phosphorous (YP) is the toxic form of elemental phosphorous and the chief constituent of firecrackers and rodenticides. In India, the rodenticide paste is frequently used for the suicidal purpose. This study is an autopsy-based observational study which describes the histopathological features of heart, lungs, liver, and kidney of fatal cases of YP poisoning. The most common autopsy features in the viscera were congestion and petechial hemorrhage. The liver histopathology findings were microvesicular steatosis (68%), hepatic necrosis (62%), macrovesicular steatosis (50%), inflammatory cells (46%), sinusoidal congestion (40%), cholestasis (32%), and toxic hepatitis (18%). Hepatic necrosis ranged from being focal to centrizonal in distribution. Congestion was the most common feature observed in the lungs and the kidney. This is the largest autopsy-based study on YP poisoning till date. The histopathological features of liver were consistent with YP poisoning whereas the findings of heart, lungs, and kidney were nonspecific in nature.

Trends in Clinical Characteristics and Short-Term Outcome of HIV-Infected Patients at a Tertiary Care Hospital in South India.

BACKGROUND: Limited information is available on changing trends in HIV positive patients treated with first-line antiretroviral therapy from India. METHODS: The clinical characteristics and short-term outcome were compared between a retrospective group enrolled between January 2006 and March 2007 (06-07 group-100 patients) and a prospective group enrolled between February 2011 and March 2012 (10-12 group-85 patients). RESULTS: Median age was 36 and 38 years in 06-07 and 10-12 groups, respectively. Median baseline CD4 count was 146 cells/mL3 in the 10-12 group, and it was not significantly different from that of 06-07 group. Tuberculosis was diagnosed 3 times more commonly in the 10-12 group. The retention proportion at the end of 10 months was 68% in the 10-12 group when compared to that of 59% in the 06-07 group. CONCLUSION: There was a trend toward improved outcome over the period of time, but the attrition rate remained high.