Prognostic and predictive significance of nuclear HIF1α expression in locally advanced HNSCC patients treated with chemoradiation with or without nimotuzumab

Background Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients.Methods Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan–Meier method. Hazard ratios were estimated by Cox proportional hazard models.Results Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42–0.93)], LRC [HR (95% CI) = 0.56 (0.37–0.86)] and OS [HR (95% CI) = 0.63 (0.43–0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37–0.82), LRC:HR (95% CI) = 0.55 (0.36–0.85) and OS:HR (95% CI) = 0.54 (0.36–0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008).Conclusions High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT.Clinical trial registration Registered with the Clinical Trial Registry of India (Trial registration identifier—CTRI/2014/09/004980).Subject terms: Tumour biomarkers, Head and neck cancer, Tumour biomarkers, Head and neck cancer, Predictive markers     

A clinical and microbiological study of puerperal sepsis in a tertiary care hospital in India

Objective: This prospective study was carried out to evaluate the clinical profile and bacterial isolates among women with puerperal sepsis in a tertiary hospital in North India.

Materials and methods: Women with puerperal sepsis (n?=?45) admitted from January 2015 to April 2016 were followed prospectively. Cultures were obtained from cervix, blood, urine, and pyoperitoneum. Initial antibiotics were cefotaxime or piperacillin with tazobactam plus amikacin plus clindamycin or metronidazole and were changed according to sensitivity.

Results: Out of 7887 deliveries during this period, 45 (0.2%) women had puerperal sepsis. 16 (35.5%) delivered in the present hospital, 25 (55.5%) at another health care facility, and 4 (8.9%) at home. Delivery was by cesarean section (CS) in 24/45 (53.3%) and vaginal in 21/45 (46.6%). Grade 1 sepsis occurred in 21, grade 2 in two, and grade 3 in 22 women. Majority (29/45 or 64.5%) had no risk factor for puerperal sepsis. There were two (4.4%) deaths and 13/45 (28.8%) had near-miss morbidity. Pathogenic bacteria were isolated in 33/45 (73.3%) in cervical swab (69%), blood, urine, or pus culture with no significant difference in the bacterial yield or species isolated between cotton or polyester swabs (p?>?.05). Escherichia coli were the commonest isolate and was sensitive to amikacin in all. Five had stillbirths and 4/40 neonates developed sepsis but recovered.

Conclusions: Escherichia coli was the commonest pathogen and was uniformly sensitive to amikacin, which may be included among the initial antibiotics to treat puerperal sepsis in India.     

Measuring Adherence by Visual Inspection of Returned Empty Gel Applicators in the CAPRISA 004 Microbicide Trial

In the CAPRISA 004 trial, adherence was estimated as the proportion of reported sex acts covered by two gel doses, which was assessed by counting returned empty gel applicators. The returned empty applicators were inspected visually in a standardized manner for residue on the outside of the applicator, as an indicator of vaginal insertion. Over 15 months, spanning 11,839 study visits by 838 women, a total of 59,800 returned empty applicators were inspected. By visual assessment, 77.5 % of these applicators appeared to have been inserted. To test the accuracy of the assessment we fitted a Cox model and found that the risk for HIV infection was doubled when less than half of the returned empty applicators had been assessed as not inserted in the vagina. Visual inspection enhanced both the accuracy of the adherence measurement and aided identification of mechanical problems with applicator use experienced by women in the trial.     

Saliva: a powerful diagnostic tool for minimal intervention dentistry

Saliva plays a vital role in oral health as patients strive to maintain a healthy dentition throughout their lives. It is natures primary defense mechanism for the oral environment, and is particularly important for protecting exposed tooth surfaces. While internal protection for dentin comes from odontoblasts and the dental pulp, the body's external protection for enamel comes from saliva. The noninvasive nature of salivary testing has made it an effective alternative to blood and urine testing and home testing kits have made it possible for people to monitor their own health using this diagnostic medium. This paper presents what saliva can reveal about general and oral health as well as highlights the current use and potential clinical and research applications, of diagnostics based on oral fluids. CLINICAL SIGNIFICANCE: Early detection always minimizes the need for more invasive treatment. It prevents oral health disease at an early stage and provides a good oral health in rejuvenated state. If you stick and follow regular professional care, prevention maintenance appointments, prevention counseling, good home care and oral hygiene, diet habits you will be free from oral health illness and you can experience the harmonious and rejuvenated state of good oral health.     

Glutathionyl hemoglobin is elevated in iron deficiency anemia

There are few good biomarkers of iron deficiency anemia (IDA). Since IDA patients have evidence for increased oxidative stress, we used mass spectrometry (MS) [i.e. matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization] to identify novel biomarkers. Using MALDI-MS, the following oxidative modifications of hemoglobin with the following mass-to-charge ratios were identified: 1,087.5 (α32-40), 1,545.7 (α17-31), 1,290.0 (β31-40) and 2,076.1 (β41-59). On electrospray ionization MS, the IDA patients had significantly elevated glutathionyl hemoglobin (GSHb) compared with the controls (16.9 ± 9.6 vs. 7.7 ± 3.7%; p = 0.002). GSHb levels correlated inversely with serum ferritin (Spearman rho -0.485; p = 0.003) and positively with serum transferrin receptor (0.460; p = 0.002). GSHb also demonstrated inverse correlations with hemoglobin (-0.512; p = 0.001), mean cell volume (-0.419; p = 0.026), serum iron (-0.446; p = 0.008) and transferrin saturation (-0.460; p = 0.008). For the first time, we show that GSHb is elevated in patients with IDA and has potential as a biomarker of this form of anemia.     

Growth patterns and anaemia status of HIV‐infected children living in an institutional facility in India

Objective  To understand the health status of HIV orphans in a well‐structured institutional facility in India. Method  Prospective longitudinal analysis of growth and anaemia prevalence among these children, between June 2008 and May 2011. Results  A total of 85 HIV‐infected orphan children residing at Sneha Care Home, Bangalore, for at least 1 year, were included in the analysis. Prevalence of anaemia at entry into the home was 40%, with the cumulative incidence of anaemia during the study period being 85%. At baseline, 79% were underweight and 72% were stunted. All children, irrespective of their antiretroviral therapy (ART) status, showed an improvement in nutritional status over time as demonstrated by a significant increase in weight (median weight‐for‐age Z‐score: ?2.75 to ?1.74, P < 0.001) and height Z‐scores (median height‐for‐age Z‐score: ?2.69 to ?1.63, P < 0.001). Conclusion  These findings suggest that good nutrition even in the absence of ART can bring about improvement in growth. The Sneha Care Home model indicates that the holistic approach used in the Home may have been helpful in combating HIV and poor nutritional status in severely malnourished orphaned children.     

Neuro-ophthalmic presentation of COVID-19 disease: A case report

COVID-19 is a respiratory virus, which has affected various organ systems as well. Here we report a neuro-ophthalmic presentation of pituitary apoplexy under the setting of COVID-19 infection in a middle-aged man who presented to ophthalmic emergency with sudden bilateral loss of vision along with a history of fever past 10 days. There was sluggishly reacting pupils and RT-PCR for COVID was positive. Imaging pointed the diagnosis as pituitary macroadenoma with apopexy. In view of pandemic situation, patient was given symptomatic treatment as per the protocols and stabilized. Vision also showed improvement to some extent and the patient is awaiting neurosurgery     

Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals

Introduction

Human APOBEC3G/F (hA3G/F) restricts retroviral replication through G-to-A hypermutations, which can generate drug-resistant progenies in vitro. The clinical relevance is still inconclusive. To bridge this gap, we aim to study the role of these hypermutations in evolution of drug resistance; we characterised hA3G/F-mediated hypermutations in the RT region of the pol gene of patients with or without antiretroviral therapy (ART).

Methods

In 88 HIV-1-positive individuals, drug resistance genotyping was carried out in plasma virus and provirus by population sequencing. Hypermutations were determined by three different approaches using Hypermut 2.0 software, cluster analysis and APOBEC3G-mediated defectives indices. Clinical and demographic characteristics of these individuals were studied in relation to these hypermutations.

Results

hA3G/F-mediated hypermutated sequences in proviral DNA, but not in plasma virus, were identified in 11.4% (10/88) subjects. Proviral hypermutations were observed more frequently in patients with ART failure than in ART-naïve individuals (p=0.03). In therapy failure patients, proviral hypermutation were associated with greater intra-compartmental genetic diversity (p<0.001). In therapy-naïve individuals, hypermutated proviral DNA with M184I and M230I mutations due to the editing of hA3G, had stop codons in the open reading frames and the same mutations were absent in the plasma virus. Only a limited concordance was found between the drug resistance mutations in plasma RNA and proviral DNA.

Conclusions

hA3G lethal hypermutation was significantly associated with ART failure in Indian HIV-1 subtype C patients. It is unlikely that viral variants, which exhibit hypermutated sequences and M184I and/or M230I, will mature and expand in vivo.     

Tumoral calcinosis in postmenopausal women in urban India: an etiopathologic evaluation of 64 cases

Tumoral calcinosis (TC) is a distinct pathologic entity of obscure etiology, characterized by soft tissue calcium deposition. We analyzed 64 cases retrieved from surgical records over the last 15 years, to assess the disease pattern and recognize the various stages of the evolution of this lesion. In our study, most patients were women (53/64 cases), 47 of whom were postmenopausal, aged 51-70 years, belonging to lower socioeconomic strata, and involved with household chores. The hip was the most frequently affected site. Repeated trauma probably triggered calcium chelation and deposition at this site. Histologically, 10 cases belonged to stage II and 54 cases to stage III. Fully developed lesions showed chips of calcium surrounded by thick fibrosis, mimicking calcified parasite like the Guinea worm. Precursor lesions seen at the periphery of the main lesion suggests a possible etiological role for trauma. Postmenopausal hormonal imbalance, along with poor nutrition and repeated trauma led to TC in our women population. Awareness of its evolution can lead to a better understanding of the disease with possible therapeutic implications.