Incidence and Patterns of Drug Resistance in Patients with Spinal Tuberculosis: a Prospective, Single-Center Study from a Tuberculosis-Endemic Country.

Background: There is paucity of data on incidence and pattern of drug resistance in spinal TB. This prospective observational study was conducted to document the incidence and drug-resistance pattern among primary and presumptive resistant cases. Methods: 59 consecutive cases diagnosed clinico-radiologically (imaging) were grouped into Group A (n = 51, primary cases) and Group B (n = 8, presumptive resistant cases) based on pre-defined criteria (INDEX-TB guidelines). Tissue samples obtained percutaneously (37.29%, 22/59) and on surgery (62.71%, 37/59) were subjected to genotypic DST (CBNAAT, LPA) and phenotypic DST (BACTEC MGIT 960 culture and sensitivity using fixed critical concentration of drugs). Results: Etiological diagnosis was ascertained in all. 13/51 (25.49%) in Group A, while 3/8 (37.5%) in Group B and 16/59 (27.12%) overall demonstrated drug resistance. 12/16 (75%) had no prior history of ATT intake. 4 demonstrated INH (Isoniazid) mono-resistance. 12 polydrug resistance demonstrated: 5MDR, 3pre-XDR, while RIF + FQ (fluoroquinolones), FQ + Lz (linezolid), only SLID (second-line injectable drugs), and only FQ resistance observed in 1 case each. Isolated RIF (Rifampicin) resistance and XDR pattern were not observed. Overall frequency of RIF resistance was 16.4% (9/55) and INH was 25% (12/48) with low-(n-2) and high-level INH resistance (n-10). Among second-line drugs, FQ resistance was more than SLID resistance and within FQ, levofloxacin resistance was more frequent than moxifloxacin. MGIT demonstrated positive growth in 16/59 samples, out of which 1 sample was positive for nontuberculous mycobacteria (M. chelonae) but on genotypic testing demonstrated MTB resistant to RIF and FQ. Conclusion: This is the first report on incidence and drug-resistant pattern in culture-positive/negative cases. High (25.49%) primary drug resistance is worrisome. This being the first study in  spinal TB cases which document prevalent drug-resistant pattern as evaluated for consecutive culture-positive/negative cases. The tissue obtained must be submitted for AFB culture and molecular tests to ascertain drug resistance in culture-positive/negative cases. However, in the presence of insufficient tissue sample histology and CBNAAT can ascertain etiological diagnosis in 100% cases. INH resistance is more than RIF with isolated RIF resistance unreported.

Hepatocellular Carcinoma-Southeast Asia Updates.

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the leading cancers worldwide. Classically, HCC develops in genetically susceptible individuals who are exposed to risk factors, especially in the presence of liver cirrhosis. Significant temporal and geographic variations exist for HCC and its etiologies. Over time, the burden of HCC has shifted from the low-moderate to the high sociodemographic index regions, reflecting the transition from viral to nonviral causes. Geographically, the hepatitis viruses predominate as the causes of HCC in Asia and Africa. Although there are genetic conditions that confer increased risk for HCC, these diagnoses are rarely recognized outside North America and Europe. In this review, we evaluate the epidemiologic trends and risk factors of HCC and discuss the prevention with surveillance and short management.

Drug Resistance in Osteoarticular Tuberculosis: A Study From an Endemic Zone.

BACKGROUND: The present study was undertaken to determine the incidence of drug resistance against anti-tubercular drugs among patients from an endemic zone.  Methodology: Forty consecutive clinico-radiologically diagnosed patients of osteoarticular tuberculosis (29: spine, 11: extraspinal) were enrolled. Pus from needle aspiration was taken in 31 cases, tissue following spinal decompression in seven, synovial in one, and sinus edge biopsy in one. The pus/tissue was subjected to acid-fast bacilli (AFB) staining and liquid culture, sensitivity to 13 anti-tubercular drugs (Isoniazid (INH), rifampicin (RIF), kanamycin (KAN), amikacin (AMK,) capreomycin (CAP), ethionamide (ETH), levofloxacin (LEV), moxifloxacin (MOX), linezolid (LNZ), para-amino-salicylic acid (PAS), bedaquiline (BDQ), delamanid (DLM), and clofazimine (CFO)) were checked, and histopathological/cytopathological examination and molecular tests were performed.   Results: The mean age of patients was 29.07(9-65) years; 21 were female and 19 were male. The diagnostic accuracy for tuberculosis was 20% by AFB smear, 65% by liquid culture, 82.5% by histopathology, and 90% by cartridge-based nucleic acid amplification testing (CBNAAT). All culture-positive isolates were identified as Mycobacterium tuberculosis with no non-tubercular Mycobacterium. The drug resistance detected on CBNAAT was 11.1%, line probe assay (LPA) first line was 15.4%, LPA second line was 4%, and liquid drug susceptibility testing (DST) 11.5%. We detected 15.4% INH resistance, 11.1% RIF, 7.6% LEV, 3.8% MOX and PAS. No resistance was detected against second-line injectable drugs (SLID), ETH, LNZ, BDQ, DLM, and CFO.    Conclusions: No single laboratory modality can ascertain the diagnosis in all cases; hence, samples should be sent for all tests in tandem. In the presence of insufficient samples, tissue may be subjected to CBNAAT and histopathology to arrive at tissue diagnosis. In this subset, overall drug resistance incidence was 12.5% (5/40) with one patient each of isolated INH and RIF resistance, one of multidrug-resistance (MDR), and two of pre-extensively drug-resistant (pre-XDR). Primary drug resistance came out to be 11.1% (4/36) with one patient each of isolated INH and RIF resistance, one of MDR, and one Pre-XDR.

Prognostic Value of IMP3 and Its Role as an Epithelial-Mesenchymal Transition Promoter in Breast Carcinoma.

Breast carcinoma is now the most common cancer in the world. In view of its high mortality, there is a need to identify new prognostic biomarkers. Both IMP3 and SLUG have been implicated in cancer metastasis. This was a retrospective study conducted on 60 breast carcinoma cases using tissue microarrays. Demographic and clinicopathological details were recorded. Immunohistochemistry for IMP3 and SLUG was performed and evaluated in terms of percentage-cell-positivity and intensity of staining. A proforma was used to store data and was analyzed using SPSS v20. IMP3 positivity was found in 87% breast carcinoma cases and was significantly associated with tumor size (p = 0.03) and TNM stage (p = 0.024). IMP3 staining intensity showed significant association with histological grade (p = 0.009), TNM stage (p = 0.036), and molecular subtype (p = 0.03). SLUG immunoexpression was seen in 90% breast carcinoma cases and was significantly associated with TNM stage (p = 0.006). SLUG staining intensity was significantly associated with age (p = 0.025) and TNM stage (p = 0.004). IMP3 and SLUG immunopositivity and their staining intensities were significantly associated (p <0.001, p <0.001). IMP3 and SLUG percentage cell positivities were also significantly correlated (p <0.001). IMP3 and SLUG are, thus, poor prognostic markers with a role in tumor invasiveness and aggressiveness via epithelial-mesenchymal transition. Hence, IMP3 and SLUG-based targeted therapies may be useful in the treatment of breast carcinoma.

Clinico-cytomorphological Spectrum of Calcinosis Cutis.

Introduction: The deposition of calcium in the skin is known as calcinosis cutis. It can affect any part of the body and can mimic soft tissue or bony lesions clinically. Aim: To describe the clinical and cytomorphologic features of calcinosis cutis on fine needle aspiration cytology smears. Materials and Methods: A total of 17 cases reported as calcinosis cutis on fine needle aspiration cytology were reviewed for the available clinical and cytological details. Results: The cohort included both adult and pediatric patients. Clinically, the lesions appeared as painless swellings of variable sizes. The common sites affected were the scrotum, iliac region, scalp, pinna, neck, axilla, elbow, arm, thigh, and gluteal region. Aspirate was chalky white, paste-like in all the cases. The cytologic evaluation revealed amorphous crystalline deposits of calcium along with histiocytes, lymphocytes, and multinucleated giant cells. Conclusions: Calcinosis cutis has a wide spectrum of clinical presentations. Fine needle aspiration cytology is a minimally invasive approach for diagnosing calcinosis cutis, thus eliminating the need for more extensive biopsy procedures.

Combination of GM CSF and carbapenem is superior to carbapenem monotherapy in difficult-to-treat spontaneous bacterial peritonitis: A randomized controlled trial.

BACKGROUND: Patients with cirrhosis and treatment non-responsive spontaneous bacterial peritonitis (SBP) have high mortality. We aimed to investigate whether GM-CSF can improve SBP response rates. PATIENTS AND METHODS: In this open-label RCT, 131 cirrhosis patients with difficult-to-treat SBP (DTT SBP) were randomized to receive meropenem alone (1 g IV thrice daily for 5 days) (MERO Group, n = 66) or in combination with GM-CSF (1.5 mcg/Kg daily IV till resolution or till 5d) (MEROGM Group, n = 65). The primary end-point was SBP early-response (reduction in absolute neutrophil count (ANC) by >25% after 48 h). Secondary end-points included SBP resolution at day 5. RESULTS: Patients in MEROGM group in comparison to MERO group had higher SBP early-response (60% vs. 31.8%; p = .001) and SBP resolution rates (55.4% vs. 24.2%; p = .0003). Patients in the combination arm also had better resolution of pneumonia {8/17 (47.05%) vs. 2/19 (10.5%), p = .02} and lower incidence of new-onset AKI (15.4% vs. 31.8%, p = .02), HE (18.5% vs. 34.8%, p = .04) and infections (21.5% vs. 37.9%, p = .05). In comparison to MERO group, 7-day survival was higher in MEROGM group (89.2% vs. 78.7%, p = .03), though the 28-day survival was comparable (78.4% vs. 71.2%; p = .66). None of the patients developed treatment-related severe adverse effects requiring discontinuation of therapy. CONCLUSIONS: The addition of GM-CSF to meropenem significantly improves response rates in DTT SBP patients within 48 h. Early use of GMCSF modulates host immune response, and enhances antibiotic response with higher SBP resolution. The use of GMCSF needs to be considered in combating difficult SBP in cirrhosis patients.

Influence of shunt occlusion on liver volume and functions in hyperammonemic cirrhosis patients having large porto-systemic shunts: a randomized control trial.

BACKGROUND AND AIMS: Spontaneous-portosystemic-shunts (SPSS) in cirrhosis deprive the liver of nutrient-rich portal blood and contribute to recurrent hepatic encephalopathy (HE). We evaluated the effects of shunt occlusion and redirecting portal blood to liver on its volume and functions. METHODS: Cirrhosis patients presenting with recurrent HE and having SPSS were randomized to receive standard medical treatment (SMT) or shunt occlusion (SO). The later was performed by plug-assisted or balloon-occluded retrograde transvenous obliteration. The primary endpoint was change in liver volume after a minimum follow-up of 3 months. Secondary objectives included clinical course, liver disease severity indices, arterial ammonia levels and bone density. RESULTS: Of 40 enrolled patients, 4 in SMT and 2 in SO group were lost to follow-up. The SO was complete in 17 and partial in one, achieving non-recurrence of HE in 17 (94.4%). In these patients, the mean liver volume increased (baseline 1040 ± 335 ml to 1132 ± 322 ml, 8.8% increase, p < 0.001) and was observed in 16/18 (88.89%) patients. In the SMT group, the liver volume decreased (baseline 988 ± 270 ml to 904 ± 226 ml, 8.6% reduction, p = 0.009) during the same period. Serum albumin increased in SO group (2.92 ± 0.40 g/dl to 3.30 ± 0.49 g/dl, p = 0.006) but reduced in SMT group (2.89 ± 0.43 g/dl to 2.59 ± 0.65 g/dl, p = 0.047). After SO, the patients showed a reduction in serum-ammonia levels (181.06 ± 86.21 to 107.28 ± 44.53 µ/dl, p = 0.001) and an improvement in MELD-Na and bone density compared to SMT group. There were no major adverse events following shunt occlusion. CONCLUSION: Occlusion of large SPSS results in improving the volume and synthetic functions of the liver by restoring hepato-petal portal flow besides reducing serum-ammonia level and recurrence of HE. CLINICALTRIALS: gov number, NCT03293459.

Dual effects of NV-CoV-2 biomimetic polymer: An antiviral regimen against COVID-19.

Remdesivir (RDV) is the only antiviral drug approved for COVID-19 therapy by the FDA. Another drug LAGEVRIO™ (molnupiravir) though has not been approved yet by FDA but has been authorized on December 23, 2021, for emergency use to treat adults with mild-to moderate COVID-19 symptoms and for whom alternative COVID-19 treatment options are not clinically appropriate. The fact is that the efficacy of RDV is, however, limited in vivo though it is highly promising in vitro against SARS-CoV-2 virus. In this paper we are focusing on the action mechanism of RDV and how it can be improved in vivo. The stability of RDV alone and on encapsulation with our platform technology based polymer NV-387 (NV-CoV-2), were compared in presence of plasma in vitro and in vivo. Furthermore, a non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV CoV-2 (Polymer encapsulated Remdesivir) in both NL-63 infected and uninfected rats was done. In addition, the antiviral activity of NV-CoV-2 and NV-CoV-2-R was compared with RDV in a cell culture study. The results are (i) NV-CoV-2 polymer encapsulation protects RDV from plasma-mediated catabolism in both in vitro and in vivo, studies; (ii) Body weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2 and NV-CoV-2-R) showed no toxic effects. (iii) Body weight measurements and survival rates of the NL-63 infected rats were similar to the uninfected rats after treatment with NV-CoV-2 and NV-CoV-2-R. Overall, the efficacy as an antiviral regimens were found in this order as below; NV-CoV-2-R > NV-CoV-2 > RDV. Our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect against different variants of the coronaviruses. First, NV-CoV-2 is an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit. All together, NV-CoV-2-R is the safest and efficient regimen against COVID-19.

PAX1 Methylation Status in Cervical Scrapes as Novel Diagnostic Biomarker in CIN 2/3 and Invasive Squamous Cell Carcinoma.

Objectives: DNA methylation of paired box-1 (PAX-1) gene has been shown to be a potential biomarker for the detection of high-grade cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer. The objective of this pilot study was to quantify and compare methylation percentage of PAX1 gene in benign cervical lesion, pre-invasive and invasive cervical cancer. Methods: A total of 200 screen positive women (VIA, VILI and Pap test) underwent colposcopy. Cervical scrapes taken were taken and stored for DNA analysis and PAX 1 methylation status. Women with Swede score of 5 or more (n = 98) were biopsied. Cervical scrapes and biopsy were taken from women with obvious cervical growth (n = 14), without prior colposcopy. Sixty women were recruited to the study and allocated into three groups on the basis of histopathology, i.e., benign cervix (Group 1; n = 20), CIN 2/3 (Group 2; n = 20) and invasive cervical carcinoma (Group; n = 20). PAX 1 methylation percentage was calculated from the DNA extracted from the cervical scrapes of the women recruited. Results: The mean PAX1 methylation percentage in benign lesions, CIN 2/3 and invasive cancer was 9.58% (SD ± 2.37%), 18.21% (SD ± 2.67%) and 24.34% (SD ± 4.09%), respectively, with p-value of < 0.001. Conclusions: PAX 1 gene methylation has a promising role in identifying high-grade lesions and invasive cancer.

Evaluation of hTERT Gene Expression and Chromosome 7 Copy Number Variation in Anal Squamous Intra-Epithelial Lesions: A Pilot Study.

Background: Akin to cervical squamous intra-epithelial neoplasia (CIN), anal squamous intra-epithelial lesion (a-SIL) is attributed to persistent infection with high-risk human papilloma virus infection. Amplification of human telomerase reverse transcriptase (hTERT) gene and aneuploidy are known to correlate with CIN evolution. It is plausible that the underlying genetic events in a-SIL are similar. We conducted this cross-sectional analytical study with the objective of determining expression of hTERT gene expression and chromosome 7, as marker of cell ploidy in a-SIL. Methods: Conventional anal cytology was performed in 86 adult consenting subjects with history of receptive anal intercourse (RAI) and 4 controls without history of RAI. Cases with a-SIL and controls were subjected to fluorescent in-situ hybridization (FISH) to evaluate hTERT gene and chromosome 7 expression, as marker of cell ploidy. Results were expressed as number of abnormal nuclei (≥3 respective signals), maximum degree of amplification, mean signals/nucleus and proportion of cases showing abnormal nuclei. Results: Twenty cases showed a-SIL; with 15 atypical squamous cells of undetermined significance (ASCUS), 3 low grade squamous intra-epithelial lesion (LSIL) and 2 cases of high-risk cytology. Expression of both hTERT gene and chromosome 7 increased from controls to ASCUS to LSIL with concomitant increase in proportion of cases having abnormal hTERT gene and chromosome 7 expression. Conclusions: Positive association of hTERT gene with a-SIL suggests its possible role in evolution of anal squamous abnormalities. Increase in chromosome 7 also correlated positively with a-SIL. These findings corroborate the similarities between squamous carcinogenesis in CIN and a-SIL.

Reversal of Feed Intolerance by Prokinetics Improves Survival in Critically Ill Cirrhosis Patients.

BACKGROUND AND AIMS: Feed intolerance (FI) is common in cirrhosis patients in intensive care units (ICU). Prokinetics are the first line treatment for FI but their efficacy and safety in critically ill patient with cirrhosis is unknown. We evaluated the role of prokinetics in reversal of FI and clinical outcomes. METHODS: Consecutive patients admitted in ICU developing new-onset FI, were randomized to receive either intravenous metoclopramide (Gr.A, n = 28), erythromycin (Gr.B, n = 27) or placebo (Gr.C, n = 28). FI was defined with the presence of 3 of 5 variables- absence of bowel sounds, gastric residual volume ≥ 500 ml, vomiting, diarrhoea and bowel distension. Primary end-point was complete resolution of FI (≥ 3 variables resolved) within 24-h and secondary end-points included resolution within 72-h and survival at 7-days. RESULTS: Of the 1030 ICU patients, 201 (19.5%) developed FI and 83 patients were randomized. Baseline parameters between the groups were comparable. Complete resolution at 24-h was higher in Gr.A (7.14%) and B (22.2%) than C (0%, p = 0.017). Overall, 58 (69.9%) patients achieved resolution within 72 h, more with metoclopramide (n = 24, 85.7%) and erythromycin (n = 25, 92.6%) than with placebo (n = 9, 32.1%, p < 0.001). The 7-day survival was better in patients who achieved resolution within 72-h (65.5 vs. 36%, p = 0.011) than non-responders. High lactate (OR-3.32, CI-1.45-7.70, p = 0.005), shock at baseline (OR-6.34, CI-1.67-24.1, p = 0.007) and resolution of FI within 72 h (OR-0.11, CI, 0.03-0.51, p = 0.04) predicted 7-day mortality. CONCLUSIONS: FI is common in critically-ill cirrhosis patients and non-resolution carries high mortality. Early recognition and treatment with prokinetics is recommended to improve short-term survival.

Gastrointestinal dysmotility is common in cirrhosis and higher incidence in critically ill patients. Promotility drugs are the first line of medication especially in ICU patients. In our study, we found that feed intolerance is present in nearly one in five critically ill cirrhosis and is associated with higher mortality. Patients who achieve resolution had an improved short-term survival. Prokinetic medications are safe in critically ill cirrhosis and help in early resolution of feed intolerance. Feed intolerance in critically ill cirrhosis should be recognized as an organ dysfunction and approaches for prevention and early diagnosis of feed intolerance could help in improving the outcomes in critical illness.

Galectin-3 and CD117 immunocytochemistry in the diagnosis of indeterminate thyroid lesions: A pilot study.

BACKGROUND: Indeterminate thyroid lesions have always been a grey zone in the field of thyroid cytopathology. Immunocytochemistry (ICC) has emerged as a promising tool to correctly classify these indeterminate thyroid lesions into benign and malignant. Hence we planned to assess a panel of immune markers in the diagnosis of indeterminate thyroid lesions consisting of Galectin-3, considered positive for malignancy and CD117 which is positive in benign follicular epithelial cells and negative in malignant lesions. METHODS: All the thyroid aspirates reported as indeterminate lesions over a period of 3 years were evaluated. Galectin-3 and CD117 immunocytochemistry was done in 50 alcohol fixed Pap stained smears of AUS/FLUS, FN/SFN and SM category lesions. The expression of both immune markers was assessed by semi-quantitative method and ICC score was calculated. RESULT: Of 50 indeterminate lesions, 29 were positive for Galectin-3 and 21 were negative. CD117 was positive in 19 cases and rests 31 were negative. With the use of this ICC panel 29/30 indeterminate lesions in which histopathological correlation was available could be recategorized correctly into benign and malignant. The combined sensitivity and specificity of Galectin-3 and CD117 for categorising the indeterminate lesions into malignant category was 100%. CONCLUSION: The combined use of positive and negative immune markers for thyroid malignancy increases the sensitivity and specificity of ICC to categorise the indeterminate thyroid lesions into benign and malignant. In cases with discordant ICC results we propose that inclusion of one additional positive and/or negative marker may resolve the diagnostic dilemma.

Evaluation of frozen section biopsy for fast track diagnosis of endometrial pathology in high-risk women with abnormal uterine bleeding.

OBJECTIVE: To study the accuracy of frozen section biopsy for endometrial pathology in high-risk women with abnormal uterine bleeding (AUB). STUDY DESIGN: A case-control study was conducted between November 2017 to April 2019, a total of 150 women with postmenopausal bleeding, perimenopausal AUB, and high-risk women of age < 40 years with AUB were recruited. All women underwent transvaginal sonography and Doppler, based on age-appropriate endometrial thickness cut-offs 80 women then underwent hysteroscopy. Based on hysteroscopy, women suspicious of malignancy were taken as cases (n = 40) and those with benign findings as controls (n = 40). All cases and controls underwent dilatation and curettage (D & C) with frozen section (FS) and routine histopathology. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR), negative LR, and overall test accuracy of FS were 90.9%, 93.19%, 83.33%, 96.19%, 13.8, 0.1 and 86.25% respectively for diagnosing endometrial hyperplasia and cancer taking histopathology as the gold standard. Correlation between frozen section biopsy and histopathology was highly significant (p < 0.001) on D & C specimens and the level of agreement was good (K = 0.778). CONCLUSION: In women suspicious of malignancy on hysteroscopy, frozen section has high accuracy on D&C specimen and can be used to diagnose endometrial hyperplasia and cancer in an effort to fast-track investigations and work-up for definitive treatment while awaiting final histopathology.

Alcohol associated liver cirrhotics have higher mortality after index hospitalization: Long-term data of 5,138 patients.

BACKGROUND/AIMS: Liver cirrhosis is an important cause of morbidity and mortality globally. Every episode of decompensation and hospitalization reduces survival. We studied the clinical profile and long-term outcomes comparing alcohol-related cirrhosis (ALC) and non-ALC. METHODS: Cirrhosis patients at index hospitalisation (from January 2010 to June 2017), with ≥1 year follow-up were included. RESULTS: Five thousand and one hundred thirty-eight cirrhosis patients (age, 49.8±14.6 years; male, 79.5%; alcohol, 39.5%; Child-A:B:C, 11.7%:41.6%:46.8%) from their index hospitalization were analysed. The median time from diagnosis of cirrhosis to index hospitalization was 2 years (0.2-10). One thousand and seven hundred seven patients (33.2%) died within a year; 1,248 (24.3%) during index hospitalization. 59.5% (2,316/3,890) of the survivors, required at least one readmission, with additional mortality of 19.8% (459/2,316). ALC compared to non-ALC were more often (P<0.001) male (97.7% vs. 67.7%), younger (40-50 group, 36.2% vs. 20.2%; P<0.001) with higher liver related complications at baseline, (P<0.001 for each), sepsis: 20.3% vs. 14.9%; ascites: 82.2% vs. 65.9%; spontaneous bacterial peritonitis: 21.8% vs. 15.7%; hepatic encephalopathy: 41.0% vs. 25.0%; acute variceal bleeding: 32.0% vs. 23.7%; and acute kidney injury 30.5% vs. 19.6%. ALC patients had higher Child-Pugh (10.6±2.0 vs. 9.0±2.3), model for end-stage liver-disease scores (21.49±8.47 vs. 16.85±7.79), and higher mortality (42.3% vs. 27.3%, P<0.001) compared to non-ALC. CONCLUSION: One-third of cirrhosis patients die in index hospitalization. 60% of the survivors require at least one rehospitalization within a year. ALC patients present with higher morbidity and mortality and at a younger age.

Are Histomorphological Features Predictive of p16 Immunopositivity Different for Oral and Oropharyngeal Squamous Cell Carcinoma?

Evidence from current studies show that squamous cell carcinomas at oral and oropharyngeal sites are distinct and unique, with their own separate etiopathogenesis, treatment, and prognosis. The aim of this work is to correlate p16 immunohistochemical expression with histomorphological features suggestive of HPV infection in oral and oropharyngeal squamous cell carcinoma. A total of 50 consecutive biopsy cases of oral squamous cell carcinoma (OSCC) and 50 consecutive biopsy cases of oropharyngeal squamous cell carcinoma (OPSCC) were evaluated for features suggestive of HPV infection like focal basaloid appearance, nests, and lobules of tumor cells with pushing borders, absence of stromal reaction, central necrosis, focal lymphoepithelial morphology, presence of koilocytes, and non-keratinizing or hybrid morphology. Immunostaining was performed using p16 monoclonal antibody (clone mouse 16P04). Only cases showing a moderate (2+) to high intensity (3+) staining in more than 75% cells were taken as p16 immunopositive. The histological features were correlated with p16 immunopositivity. A total of 18/50 (36%) cases of oral squamous cell carcinoma and 27/50 (54%) cases of oropharyngeal squamous cell carcinoma were p16 immunopositive. On statistical analysis, only nests/lobules with pushing borders were found to have a significant correlation with p16 immunopositivity (P value = 0.0012) for OSCC cases. For OPSCC cases, four histological features namely nests and lobules with pushing borders (P value = 0.0001), focal basaloid appearance (P value = 0.0041), lymphoepithelial morphology (P value = 0.0029), and non-keratinizing/hybrid morphology (P value = 0.0141) had a significant correlation with p16 immunopositivity. Histomorphological features are more helpful in predicting p16 immunopositivity in OPSCC than OSCC.

A new normal with cataract surgery during COVID-19 pandemic.

Cataract is the second leading cause of preventable blindness on the globe. Several programs across the country have been running efficiently to increase the cataract surgical rates and decrease blindness due to cataract. The current COVID-19 pandemic has led to a complete halt of these programs and thus accumulating all the elective cataract procedures. At present with the better understanding of the safety precautions among the health care workers and general population the Government of India (GoI) has given clearance for functioning of eye care facilities. In order to facilitate smooth functioning of every clinic, in this paper, we prepared preferred practice pattern based on consensus discussions between leading ophthalmologists in India including representatives from major governmental and private institutions as well as the All India Ophthalmological Society leadership. These guidelines will be applicable to all practice settings including tertiary institutions, corporate and group practices and individual eye clinics. The guidelines include triage, use of personal protective equipment, precautions to be taken in the OPD and operating room as well for elective cataract screening and surgery. These guidelines have been prepared based on current situation but are expected to evolve over a period of time based on the ongoing pandemic and guidelines from GoI.

Cytological diagnosis of juvenile xanthogranuloma: A rare histiocytic disorder.

Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhan cell histiocytic disorder, which is mostly confined to skin of head and neck. It is a self-limiting benign condition, which does not require surgery. We present a case of 8-month-old girl child with multiple yellowish brown colored papules over scalp, face, and neck. A clinical diagnosis of cutaneous mastocytosis was made. Fine-needle aspiration cytology (FNAC) smears showed foamy macrophages along with mixed inflammatory infiltrate and few touton giant cells. A diagnosis of JXG was rendered which was confirmed on histopathology and immunohistochemistry.Juvenile xanthogranuloma can be diagnosed on FNAC based on its characteristic cytologic features; however, it requires a high index of suspicion by cytopathologist. Cytological diagnosis of JXG can save the patient from unnecessary surgical biopsy or excision.

Implementation of the MILAN system for reporting salivary gland cytopathology: Interobserver concordance and cytohistological correlation of discordant cases.

BACKGROUND: Fine needle aspiration cytology (FNAC) plays a pivotal role in evaluating salivary gland (SG) tumors. Several studies have shown diagnostic utility of MILAN system for reporting salivary gland cytopathology (MSRSGC) by examining risk of malignancy but only an occasional study has focused on interobserver variability. Hence, the present study was undertaken to assess the agreement among cytopathologists with varying experience in SG cytopathology using MSRSGC and to re-evaluate discordant cytohistological diagnoses for possible causes of misinterpretation. METHODS: All SG lesions subjected to FNAC over a period of 3½ years were studied. The cases were critically reviewed by 2 pathologists with variable experience in cytopathology using MSRSGC and concordance level among them was calculated. Cytohistological discordant diagnoses were reclassified and possible causes of misinterpretation during routine reporting were evaluated. RESULTS: Of 150 SG aspirates categorized according to MSRSGC, diagnostic disagreement between 2 pathologists was found in 10. Unweighted Cohen's Kappa score between consultant and resident was 0.812 (high). Among 55 cases with histological correlation, cytohistological discordance was seen in 12. True pitfalls constituted 50% of discordant cases while rest 50% were attributed to practical issues (turnaround time and heavy case load) during routine reporting. CONCLUSION: MSRSGC can be used with good reproducibility between observers with variable cytopathology experience. Heterogeneous nature of SG neoplasm is a known pitfall in FNA diagnosis of SG neoplasms. During routine reporting turnaround time, heavy case load and reporting by cytopathologists with variable experience add on to challenges faced in reporting cytopathology of SG neoplasm.