Histological risk score and its role in predicting recurrence in early-stage oral squamous cell carcinomas

Context: Oral squamous cell carcinoma (OSCC) comprises more than 90% of oral cancers and is the most common carcinoma affecting the oral cavity. Early stage T1/T2 OSCC have a heterogeneous prognosis and a significant number of patients develop loco regional recurrence (LRR) and have reduced disease free survival (DFS) with increased disease related mortality. Aims and Objectives: To assess the impact of the three parameters used in Brandwein-Gensler risk model along with lympho-vascular invasion (LVI), depth of invasion (DOI) and lymph node metastases in predicting LRR in early stage OSCC. Materials and Methods: This was a retrospective study on early stage T1/2 OSCC patients over a period of 2 years who received treatment by surgical resection and had follow-up data. LRR was assessed based on recurrence of OSCC at the initial site or in regional lymph nodes. Results: Out of 1135 OSCC cases during our study period a total of 207 cases befitted our inclusion criteria. Recurrence was noted in 113 (54.6%) cases. Univariate analysis identified LVI (P < 0.00001), DOI (P < 0.00001), nodal involvement (P < 0.00001), worst pattern of invasion (WPOI) (P < 0.00001), lymphocytic host response (LHR) (P = 0.004), perineural invasion (PNI) (P = 0.012) as strong statistically significant risk factors for LRR. Conclusion: Adequate assessment of simple parameters on routine H and E by incorporating Brandwein-Gensler histological risk scoring model at the initial presentation can help prognosticate and predict LRR and select patients for post-surgical adjuvant therapy.

Geriatric intertrochanteric fractures – A challenge to manage

Background: Intertrochanteric fractures are among the frequently seen fractures in the elderly population. Treating these fractures is very challenging considering the fact that the quality of bone is poor and highly osteoporotic. The high failure rates with dynamic hip screw (DHS) especially in unstable fractures lead to the development of intramedullary devices such as proximal femoral nail (PFN) which has got multiple advantages over DHS. Materials and Methods: This prospective study included 30 patients above the age group of 60 years with unstable intertrochanteric fractures conducted in a tertiary institute between February 2021 and June 2022. Results were analyzed clinically and radiologically using the Modified Harris hip score. Results: Patients’ age group was 61–85 years with a mean age of 69 years, comprising 63% female and 37% male. The average Harris hip score was 83.76 at 24 weeks’ follow-up with 33.33% excellent, 56.66% good, 3.33% fair, and 6.67% poor. Postoperative complications included revision surgery in two patients, superficial infection in one patient, Z effect in one patient, peri-implant fracture in one patient. Conclusion: Treatment with PFN for unstable intertrochanteric fracture has the advantages of closed reduction, less tissue damage, early rehabilitation, and return to work. Osteosynthesis with short PFN resulted in good-to-excellent functional and radiological outcomes.

Placement of Oral Formulations of Brivaracetam in Various Patient Profiles: An Indian Perspective

Brivaracetam (BRV), an analog of levetiracetam (LEV), lowers seizure frequency through a unique mechanism. Although BRV is approved for focal epilepsy in patients aged >1 month (by the US Food and Drug Administration) or >16 years (in India), clinical studies have suggested its potential role in other indications such as generalized seizures, secondarily generalized tonic-clonic seizures, and drug-resistant focal epilepsy, and in certain special populations. Here, we discuss the potential role of BRV in different patient populations and present expert opinions for positioning the pre-existing and newly available oral formulations of BRV to aid both clinicians and diverse patient groupswith a simple and easy dosing and titration-based treatment, including safe and effective switching from LEV to BRV.

An Observational Study of Demography, Clinical Characteristics, and Outcomes, of Dismembered Pyeloplasty for the Management of Pelviureteric Junction Obstruction.

Ureteropelvic junction (UPJ) obstruction (UPJO) leads to a functionally significant impairment of urinary transport from the renal pelvis to the ureter. Recently, the increasing use of maternal antenatal ultrasonography (USG) has led to increased diagnosed cases of UPJO. In a setup like ours, where patients are mainly from a lower middle class, minimally invasive techniques are still costly and long-term data for their outcomes are still awaited. The aim of this study is to find the outcome of the gold standard operation, i.e. open pyeloplasty, for the patients of UPJO, with objective criteria of severity, renal function, clinical features, and complications. MethodsThis prospective observational study was done from September 2016 to October 2018 8 after taking ethical clearance from the institutional review board. This study included 25 patients of UPJO who were managed surgically with open dismembered Anderson Hynes pyeloplasty with DJ stenting were followed up for three months. UPJO patients were included in the study who underwent USG and renal scan, pre-operatively and at the follow-up time of 3 months. Categorical variables will be presented in numbers and percentages (%), and continuous variables will be presented as mean ± SD and median. Quantitative variables will be compared using independent t-test / Mann-Whitney Test. Qualitative variables will be correlated using the Chi-Square test. A p-value of < 0.05 will be considered as statistically significant. ResultsThe mean age of the patients in our study was 15.93 ± 15.73 years. Overall, significant improvement in clinical features, grade of hydronephrosis, and renal function, was seen three months after the operation (p<0.05) with minimal complications. ConclusionsWith a success rate of more than 92% as seen in our study, open Anderson Hynes pyeloplasty procedure holds its importance for the treatment of UPJO in the present era of minimally invasive surgery.

Carcinoma vulva patterns of recurrence and treatment outcomes: A single-institution experience

Aim: The aim of this study was to evaluate the patterns of recurrence and outcomes in patients with vulvar cancer treated with surgery, with or without postoperative radiotherapy (RT) or RT alone. Materials and Methods: The hospital records were retrospectively analyzed from February 2007 to May 2016. All patients that had biopsy-proven carcinoma vulva were included for analysis. Surgery was done by simple or radical vulvectomy with or without lymph node dissection. Radical RT dose was 60 Gy (photons alone or with electron boost). Adjuvant RT was administered in case of node positivity or positive margins. Results: A total of 76 patients were diagnosed as squamous cell carcinoma of vulva. The median age was 59 years. About 59 patients were treated by surgery and 17 patients were treated by radical RT. The most common stage was IB. Adjuvant RT was administered in 10 patients. About 13 patients (22%) underwent inguinal lymphadenectomy. At a median follow-up of 35 months, 49 patients (64.4%) were alive, 27 died, and 6 patients were lost to follow-up. Locoregional recurrence rate was 24.5% in radical surgery group, 12% in surgery plus adjuvant RT group, and 47% in radical RT group. Distant metastasis rate was 4%. The progression-free survival at 3 years was 45.3% and 35.5% in the surgery group and radical RT group, respectively. Conclusion: Surgery resulted in favorable local control rates in early-stage carcinoma vulva. Adjuvant RT is indicated in case of nodal positivity or positive margins. Radical RT can be considered as an alternative in patients with comorbidities

Cultural conditions on the production of extracellular enzymes by Trichoderma isolates from tobacco rhizosphere

Abstract Twelve isolates of Trichoderma spp. isolated from tobacco rhizosphere were evaluated for their ability to produce chitinase and β-1,3-glucanase extracellular hydrolytic enzymes. Isolates ThJt1 and TvHt2, out of 12 isolates, produced maximum activities of chitinase and β-1,3-glucanase, respectively. In vitro production of chitinase and β-1,3-glucanase by isolates ThJt1 and TvHt2 was tested under different cultural conditions. The enzyme activities were significantly influenced by acidic pH and the optimum temperature was 30 °C. The chitin and cell walls of Sclerotium rolfsii, as carbon sources, supported the maximum and significantly higher chitinase activity by both isolates. The chitinase activity of isolate ThJt1 was suppressed significantly by fructose (80.28%), followed by glucose (77.42%), whereas the β-1,3-glucanase activity of ThJt1 and both enzymes of isolate TvHt2 were significantly suppressed by fructose, followed by sucrose. Ammonium nitrate as nitrogen source supported the maximum activity of chitinase in both isolates, whereas urea was a poor nitrogen source. Production of both enzymes by the isolates was significantly influenced by the cultural conditions. Thus, the isolates ThJt1 and TvHt2 showed higher levels of chitinase and β-1,3-glucanase activities and were capable of hydrolyzing the mycelium of S. rolfsii infecting tobacco. These organisms can be used therefore for assessment of their synergism in biomass production and biocontrol efficacy and for their field biocontrol ability against S. rolfsii and Pythium aphanidermatum infecting tobacco.

Genetic association study of P2x7 A1513C (rs 3751143) polymorphism and susceptibility to pulmonary tuberculosis: A meta-analysis based on the findings of 11 case–control studies

Objective To summarize the precise association between pulmonary tuberculosis (PTB) and P2x7 A1513C gene polymorphism. Methods PubMed and Google Scholar web-databases were searched for the studies reporting the association of P2x7 A1513C polymorphism and PTB risk. A meta-analysis was performed for the selected case–control studies and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all the genetic models. Results Eleven studies comprising 2 678 controls and 2 113 PTB cases were included in this meta-analysis. We observed overall no significant risk in all the five genetic models. When stratified population by the ethnicity, Caucasian population failed to show any risk of PTB in all the genetics models. In Asian ethnicity, variant allele (C vs. A: P = 0.001; OR = 1.375, 95% CI = 1.159–1.632) and heterozygous genotype (AC vs. AA: P = 0.001; OR = 1.570, 95% CI = 1.269–1.944) demonstrated significant increased risk of PTB. Likewise, recessive genetic model (CC + AC vs. AA: P = 0.001; OR = 1.540, 95% CI = 1.255–1.890) also demonstrated increased risk of PTB in Asians. Conclusions Our meta-analysis did not suggest the association of P2x7 A1513C polymorphism with PTB risk in overall or separately in Caucasian population. However, it plays a significant risk factor for predisposing PTB in Asians. Future larger sample and expression studies are needed to validate this association.

Genetic association study of P2x7 A1513C (rs 3751143) polymorphism and susceptibility to pulmonary tuberculosis: A meta-analysis based on the findings of 11 case-control studies

OBJECTIVE@#To summarize the precise association between pulmonary tuberculosis (PTB) and P2x7 A1513C gene polymorphism.@*METHODS@#PubMed and Google Scholar web-databases were searched for the studies reporting the association of P2x7 A1513C polymorphism and PTB risk. A meta-analysis was performed for the selected case-control studies and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all the genetic models.@*RESULTS@#Eleven studies comprising 2678 controls and 2113 PTB cases were included in this meta-analysis. We observed overall no significant risk in all the five genetic models. When stratified population by the ethnicity, Caucasian population failed to show any risk of PTB in all the genetics models. In Asian ethnicity, variant allele (C vs. A: P = 0.001; OR = 1.375, 95% CI = 1.159-1.632) and heterozygous genotype (AC vs. AA: P = 0.001; OR = 1.570, 95% CI = 1.269-1.944) demonstrated significant increased risk of PTB. Likewise, recessive genetic model (CC + AC vs. AA: P = 0.001; OR = 1.540, 95% CI = 1.255-1.890) also demonstrated increased risk of PTB in Asians.@*CONCLUSIONS@#Our meta-analysis did not suggest the association of P2x7 A1513C polymorphism with PTB risk in overall or separately in Caucasian population. However, it plays a significant risk factor for predisposing PTB in Asians. Future larger sample and expression studies are needed to validate this association.

Genetic variation in nucleotide excision repair pathway genes influence prostate and bladder cancer susceptibility in North Indian population.

BACKGROUND: Inherited polymorphisms of XPD and XPC genes may contribute to subtle variations in NER DNA repair capacity and genetic susceptibility to development of urological cancer such as prostate and bladder cancer. MATERIALS AND METHODS: We genotyped four Single Nucleotide Polymorphs (SNPs) of the DNA repair gene XPD and XPC in 195 prostate cancer (PCa) and 212 bladder cancer (BC) patients and 250 healthy controls from the same area. XPD Exon 10 (G>A) by amplification refractory mutation system and Exon 23 (A>C), XPC Intron 9 (Ins/Del) and Exon 15 (A>C) were genotyped by PCR-RFLP. RESULTS: Variant genotype of XPC demonstrated association with PCa as well as in BC (P, 0.013; P, 0.003). Combined genotype (GA+AA) revealed association with PCa and in BC (P, 0.012, P, 0.002). Variant allele also demonstrated risk in both the cancer. Diplotype of XPD and XPC was associated with a significant increase in PCa and BC risk. Variant (+/+) genotype of XPC intron 9 shown increased risk with PCa and in BC (P, 0.012; P, 0.032). CC genotype of XPC exon 15 revealed increase risk (P, 0.047) with PCa not in BC. In clinopathological grade variant allele of XPC intron 9 and 15 demonstrated risk with high grade of tumor and bone metastasis of PCa. In BC variant allele of XPD exon 10 and 15 also shown association with tumor grade. XPC intron 9 influences the risk of BC in former tobacco users in BC. CONCLUSIONS: Our result support that SNPs in XPD and XPC gene may reduce NER repair capacity and play a major role for PCa and BC in North India.

Polymorphisms in base-excision & nucleotide-excision repair genes & prostate cancer risk in north Indian population.

Background & objectives: Genetic variation in the DNA repair genes might be associated with altered DNA repair capacities (DRC). Reduced DRC due to inherited polymorphisms may increase the susceptibility to cancers. Base excision and nucleotide excision are the two major repair pathways. We investigated the association between two base excision repair (BER) genes (APE1 exon 5, OGG1 exon 7) and two nucleotide excision repair (NER) genes (XPC PAT, XPC exon 15) with risk of prostate cancer (PCa). Methods: The study was designed with 192 histopathologically confirmed PCa patients and 224 age matched healthy controls of similar ethnicity. Genotypes were determined by amplification refractory mutation specific (ARMS) and PCR-restriction fragment length polymorphism (RFLP) methods. Results: Overall, a significant association in NER gene, XPC PAT Ins/Ins (I/I) genotype with PCa risk was observed (Adjusted OR- 2.55, 95%CI-1.22-5.33, P=0.012). XPC exon 15 variant CC genotypes presented statistically significant risk of PCa (Adjusted OR- 2.15, 95% CI-1.09-4.23, P=0.026). However, no association was observed for polymorphism with BER genes. Diplotype analysis of XPC PAT and exon 15 revealed that the frequency of the D-C and I-A diplotype was statistically significant in PCa. The variant genotypes of NER genes were also associated with high Gleason grade. Interpretation & conclusions: The results indicated that there was a significant modifying effect on the association between genotype XPC PAT and exon 15 polymorphism and PCa risk which was further confirmed by diplotype analysis of XPC PAT and exon 15 in north Indian population.

Management of Raised Intracranial Pressure.

Appropriate management of raised intracranial pressure begins with stabilization of the patient and simultaneous assessment of the level of sensorium and the cause of raised intracranial pressure. Stabilization is initiated with securing the airway, ventilation and circulatory function. The identification of surgically remediable conditions is a priority. Emergent use of external ventricular drain or ventriculo-peritoneal shunt may be lifesaving in selected patients. In children with severe coma, signs of herniation or acutely elevated intracranial pressure, treatment should be started prior to imaging or invasive monitoring. Emergent use of hyperventilation and mannitol are life saving in such situations. Medical management involves careful use of head elevation, osmotic agents, and avoiding hypotonic fluids. Appropriate care also includes avoidance of aggravating factors. For refractory intracranial hypertension, barbiturate coma, hypothermia, or decompressive craniectomy should be considered.

Bioactive actinomycetes from Krishna River sediments of Andhra Pradesh.

Sediment samples from Krishna River at Nagayalanka of Andhra Pradesh, India were investigated as a source of actinomycetes to screen for the production of novel bioactive compounds. During our investigation on fresh water actinomycetes from 5 different river sediment samples, a total of 80 actinomycetes were isolated. Out of these 80 isolates, 30 isolates which showed distinct macromorphological characteristics were selected. The antimicrobial and enzymatic activities were studied for all the 30 isolates. The preliminary study for antimicrobial activity by cross streak method indicated that 16 isolates (53.3%) have excellent antagonistic properties. All these 16 isolates were subjected to detailed submerged fermentation studies. It was observed that 12 isolates (40.0%) exhibited antibacterial activity, 9 isolates (30.0%) showed antifungal activity while 5 isolates (16.6%) showed both antibacterial and antifungal activities. All the 30 isolates were also subjected for the determination of enzymatic activities 25 isolates (83.3%) exhibited amylolytic activity while 27 isolates (90.0%) showed proteolytic activity. Among these isolates, six promising isolates were selected for detailed morphological, cultural, physiological and biochemical studies. It was established that these isolates belong to the Streptomyces genus by virtue of their cell wall composition pattern and were identified as strains of different Streptomyces species like S. rochei, S. alanosinicus, S. erumpens, S. griseoplanus, S. gancidicus and S. nigrogriseolus.

Bioactive rare actinomycetes from indigenous natural substrates of Andhra Pradesh.

This investigation reports the occurrence of bioactive rare actinomycetes from different indigenous natural substrates of Andhra Pradesh. During the course of our investigation on 20 terrestrial soil samples, 5 marine samples and 3 fresh water samples, a total of 92 rare actinomycetes belonging to Micromonospora, Nocardia, Actinomadura and Thermoactinomyces genera were isolated. The antimicrobial and enzymatic activities were studied for all the isolates. The antibacterial and antifungal activities were studied preliminarily by cross-streak method followed by submerged fermentation studies employing standard cup-plate method for the assay. It was found that 34 isolates (36.95%) showed excellent antibacterial activity and 29 isolates (31.52%) showed good antifungal activity. Proteolytic and amylolytic activities were also studied. It was observed that 79 isolates (85.86%) showed proteolytic activity and 75 isolates (81.52%) showed amylolytic activity.

Use of complement receptor 1 (CD35) assay in the diagnosis and prognosis of immune complex mediated glomerulopathies.

Complement Receptor 1 (CR1) is a polymorphic glycoprotein expressed on erythrocytes, leukocytes and glomerular podocytes and has a major role in immune complex processing. In addition, it regulates the complement cascade activation by preventing formation of classical and alternative pathway convertases and by acting as a cofactor for Factor I mediated cleavage of C3. In this study, we have examined the expression of erythrocyte CR1 (E-CR1) and glomerular CR1 (G-CR1) in different kinds of nephropathies using ELISA and immunofluorescence microscopy to understand their role in immune complex (IC) mediated renal diseases. E-CR1 was significantly reduced in all categories of lupus nephritis in comparison to normal subjects and non-IC renal diseases. However, other IC mediated diseases like IgA nephropathy and membranoproliferative glomerulonephritis had normal E-CR1 levels. G-CR1 showed distinct differences between IC and non-IC mediated diseases. G-CR1 was virtually absent in lupus kidneys. In other IC mediated diseases, there was a correlation of G-CR1 expression to the IC and complement fragment deposition. G-CR1 serves as a useful diagnostic marker for IC mediated diseases while E-CR1 is useful as a prognostic marker to monitor the course of disease after the treatment has initiated.

Sown a seed of Ayurveda in the Nizam dominion.

In the name of Trillinga Ayurveda Vidya Peetham a seed for Ayurveda with a school & free Ayurveda dispensary along with a Sanskrit school was sowed at Warangal by some eminent devoted private practitioners of Ayurveda and Philanthropists. The city of Warangal is a historical place and once a capital of Kakatiya Kingdom, though it was part and parcel of Nizam dominion. In fact such steps taken by Private Organisations for establishment of Ayurvedic system of Medicine in Hyderabad and in Andhra region at Bejwada is appreciable.

Dawn of Ayurveda during the reign of Nizam VII of Hyderabad.

Mir Osman Ali Khan Bahadur, the Nizam VII ruled the Hyderabad State for about 38 years. In those days Ayurveda was flourishing in the state due to efforts of many Ayurvedic physicians, scholastic teachers, distinguished patrons and well-wishes who worked together with devotional spirit to make Ayurveda available to the people of the state to provide care for the diseases. Nizam Ayurveda Vaidya Sangh started Nizam Ayurvedic college and Nizam Ayurvedic Sadar Dawakhana in Hyderabad city under their management in the year 1934 as a private institution, which was inaugurated in the same year by Azam Jah Bahadur, the Prince of Berar. Consequent upon the inauguration, the Nizam Government accorded sanction of an amount of Rs. 200/- per month for Ayurveda. Thus the seed of Ayurveda was sown during the reign of Nizam VII in the Hyderabad state.

Effect of nitrate on nitrogen fixation and nitrate assimilation in Azorhizobium-Sesbania rostrata symbiotic system.

Root nodule formation was inhibited by 30% and 50% respectively at low concentration of 1 mM and 2 mM nitrate, while stem nodule formation was enhanced by 50% only at 1 mM nitrate. The nodule specific nitrogenase activity decreased with the increasing concentration of nitrate. At 1 mM nitrate nitrogenase activity per plant stem nodule was not affected, but it was less than 50% in the root nodules as compared to control. Increasing concentration of nitrate increased in vivo activity of nitrate reductase (NR) significantly in stem, root nodules and leaves. Nodule cytosolic NR utilized both NADH and succinate as electron donor, but not reduced MV. However bacteroidal NR utilised reduced MV as reductant more efficiently than succinate.

Effect of combined nitrogen on the expression of nitrate reductase and nitrite reductase in Azorhizobium caulinodans.

In aerobically grown Azorhizobium caulinodans strain IRBG 46, in vivo expression of nitrate reductase (NR) and nitrite reductase (NiR) requires the presence of either nitrate or nitrite. On the contrary mere microaerobic conditions are sufficient for the expression of NR and NiR, however, addition of nitrate to the growth medium enhanced the activities of the enzymes. Optimum concentration of nitrate for maximum expression of NR and NiR activities was different in aerobic and microaerobic conditions. Nitrite was released into the medium both in aerobic and microaerobic conditions beyond a particular concentration of nitrate in the medium. Dissimilatory nitrate reduction was affected to a lesser extent by ammonium compared to assimilatory nitrate reduction.

Arsenic: the forgotten poison?

Chronic arsenic poisoning is an uncommon cause of peripheral neuropathy in Jamaica. A patient with this disorder is described. The insidious nature of chronic arsenic poisoning, with its disabling complications, is emphasised.

Endoscopic sclerotherapy of bleeding oesophageal varices in Jamaica

The results of oesophageal sclerotherapy (OS) in 18 patients with recurrent bleeding varices are compared with 15 patients treated medically. The total transfusion requirement pre sclerotherapy was 112 units of blood (mean 6/patient) which decreased to 46 units ( mean 2.5) after sclerotherapy treatment was started (p=0.005). In the medically treated group, total transfusion was 74 units (mean 5 units/patient). One hundred and forty-three infection sclerotherapy session were given, and all but one patient had significant reduction or eradication of varices. Three patients died of recurrent bleeding (17%) and one other required surgery. In the medically treated group, 3 patients died of bleeding (20%). Complications of sclerotherapy included mild bleeding (39%), chest pain (28%) and oesophageal ulcer (5.5%). OS reduces transfusion requirements in patients with recurrent variceal bleeding