Our Experience with Sinonasal Glomangiopericytoma in North India: A Case Series.

Glomangiopericytoma (GPC) is a rare benign sinonasal tumor originating from Zimmerman's Pericytes surrounding capillaries and accounting for less than 0.05% of all sinonasal tumors. Glomangiopericytoma has low malignant potential (5-10%) and is mostly diagnosed in the 6th or 7th decade of age with slight female preponderance. We presented here a case series of 5 patients with sinonasal GPC. This research was conducted at a tertiary healthcare centre in North India. In our case series, all the patients were evaluated and underwent endoscopic surgical resection. All patients underwent digital subtraction angiography (DSA) and preoperative embolization. The coblation technique used for haemostasis proved very effective and time-saving. All patients exhibited cytoplasmic SMA positivity (a marker of GPC) and CD34 negativity, while one patient exhibited a high Ki-67 index (> 10%), which is a predictor of aggressive tumor behavior. None of the patients showed any recurrence in follow-up. We recommend performing complete endoscopic surgical excision to prevent recurrence. The use of DSA, preoperative embolization, and intraoperative use of the coblation technique provides a cleaner surgical field and reduced operating time.

A Rare Case of Retropharyngeal Abscess in a 3 Month Old Male Infant: Case Report and Review of Literature.

Retropharyngeal abscess (RPA) is a rare, potentially fatal condition found more frequently in young children usually who were having a history of Upper respiratory infection. RPA is an acute suppurative infection of the retropharyngeal space. In view of scarce literature availability and atypical presentation in infants, it poses a definitive diagnostic dilemma to the clinicians. Here, we are reporting a three-month-old male infant presented with feeding difficulty, obstructive sleep apnea and intermittent inspiratory stridor. Child was managed in a pediatric ICU with a multidisciplinary approach which involved pediatrician, otorhinolaryngologist pediatric anesthesiologist, microbiologist, and radiologist. With the recent advances, early radio imaging have a vital role in diagnosing the condition and also helps in planning of surgery. Prompt diagnosis and surgical management with appropriate antimicrobial therapy for this condition is imperative to prevent complications such as airway obstruction and mediastinitis. Timely surgical intervention, preferably intraoral transpharyngeal approach, to drain the abscess is recommended.

Gestational Mild COVID-19 Infection Associated Neonatal Hearing Loss: A Case-Control Study from North India.

COVID-19 infection during pregnancy is potentially dangerous to neonatal hearing, as it is the period of organogenesis, and associated hyperthermia may cause vascular damage, disruption of cell migration, and death of the dividing neuroblasts. To investigate the possible association between neonatal hearing loss and gestational mild COVID-19 infection. A prospective case-control study was conducted at a tertiary healthcare centre in North India from March 2020 to Oct 2022. Cases included the neonates born to COVID-19-positive mothers were subjected to hearing screening at 1, 3 and 6 months using otoacoustic emission (OAE) and automated auditory brainstem response (AABR). Similar protocol was applied to controls, i.e., neonates borne to mothers with no gestational history of COVID infection. Results were analyzed statistically. Our study reported that the statistical difference between groups A (n = 942) and B (n = 942) for gestational COVID-19 infection and neonatal hearing loss was insignificant at 1 month (p-value 0.272 for OAE and p-value 0.634 for AABR) and also insignificant at 3 and 6 months (p-value 0.679 for AABR, for both). The association between gestational mild COVID-19 infection during gestation and neonatal hearing loss is statistically insignificant at initial screening as well as sequential screenings.

Endoscopy Assisted Removal of Post Traumatic Impacted Foreign Body in the Nose Extending into Opposite Parapharyngeal Space.

The head and neck region is a complex anatomical area with vulnerable nervous and vascular structures, auditory and visual organs and upper aero-digestive tract. Penetrating foreign bodies of head and neck region are not uncommon and pertain mostly to wood, metal and glass (Levine et al. in Am J Emerg Med 26:918-922, 2008). This case report describes an airborne high velocity foreign body blown off from a lawn mower penetrating the left side of the face, penetrating deep into nasopharynx and opposite parapharyngeal space through paranasal sinuses. A multidisciplinary team managed this case successfully, avoiding injuries to adjacent vital skull base structures.

Of Eagle's Syndrome and Finding Some Clarity on Its Management.

Eagle's Syndrome is a much discussed yet controversial and debatable diagnosis of exclusion which is treated by many specialities with often unsatisfactory results. Due to entrapment/impingement on surrounding neurovascular structures by elongated styloid process patient may present with multitude of symptoms. Treatment is controversial and opinions are divided on choice of conservative and surgical management. Aim was to study outcomes of conservative and surgical modalities of treatment of Eagle's Syndrome and bring some clarity on management, what to offer, to whom and when. This prospective observational descriptive study included 15 patients of Eagle's Syndrome, 7 were treated with conservative method and 8 underwent resection of styloid process with intraoral approach. With objectives in mind to study efficacy of both management modalities, pain visual analogue scale (VAS) scores were recorded pre-intervention, post-intervention and during follow up on 1, 3 and 6 months and compared. Conservative management resulted in up to 70% reduction in pain VAS scores till 3 months of therapy (mean pre-intervention score being 3.71, 3 months-1, 6 months-1.29), while surgical modality resulted in nearly 99% reduction in mean pain VAS scores up to 3 months and even improved after 6 months (mean pre-intervention score being 6.75, 3 months-0.5, 6 months-0.13). With this we can conclude that conservative management provide satisfactory short-term (up to 3 months) results but recurrences are known, while surgical resection of elongated styloid process gives better long-term results (6 months and beyond).

Tracheostomy: Open Surgical or Percutaneous? An Effort to Solve the Continued Dilemma.

Due to lack of globally standardized guidelines and clarity on indications, patient selection, intra-operative preparations, technique, complications, postoperative care and decannulation protocols, percutaneous tracheostomy (PT) has come in vogue as compared to standard open surgical tracheostomy (OST). PercuTwist and guide wire dilatational method (GWDF), techniques of PT, offer lesser operative time and ease of surgery being a bedside procedure. There seems to be paucity of Indian literature on rising trend of increasing indications, post-operative care, management of complications and outcomes of tracheostomy. And thus, there arises a felt need to envisage a study in tertiary care setup targeting these issues and to question the so far unchallenged acceptance of new techniques and technology. Our aim is to study the recent trend of indications, complications, and outcomes of both OST and PT in a cohort of Indian patients who underwent tracheostomy. 80 patients with mean age of 59.0 ± 15 years underwent tracheostomy (OST: 48 (60%), PT: 32 (40%), and among PT, PercuTwist: 16 (50%), GWDF: 16 (50%)) for various indications with objectives to compare operative time, complications and decannulation rates of tracheostomy surgery, within the follow up period of 3 months. Most common indication of elective tracheostomy was prolonged ventilation, and for emergency ones, upper airway obstruction. Mean operative time taken by all the three techniques was comparable, i.e., 16.3 v/s 15 v/s 15.3 min (Open v/s PT GWDF v/s PT PercuTwist). Most common intra-operative complication of OST was haemorrhage (16.3%) and that of PT was false passage (8.8%). Early post-operative complications were haemorrhage (OST: 3.75%, PT: 1.25%) and tube blockage and dislodgement (equal distribution among OST and PT). Late post-operative complications were stomal granulations in PT: 7.5%. Outcomes of tracheostomy were significantly better with OST (36 (45%)) than PT (14 (17.5%)). In PT group, PercuTwist fared better than GWDF in terms of lesser complications (PercuTwist: 10%, GWDF: 18.6%) and better decannulation rates (PercuTwist: 13.6%, GWDF: 3.75%). Most common indication for tracheostomy remains prolonged intubation; complication of OST is intra and early post-operative haemorrhage and that of PT being tube dislodgement and blockage. Outcomes in form of successful decannulation are with OST.

Reply to the Comment on "Melanisation of Aspergillus terreus-Is Butyrolactone I Involved in the Regulation of Both DOPA and DHN Types of Pigments in Submerged Culture? Microorganisms 2017, 5, 22".

n/a.

Melanisation of Aspergillus terreus-Is Butyrolactone I Involved in the Regulation of Both DOPA and DHN Types of Pigments in Submerged Culture?

Pigments and melanins of fungal spores have been investigated for decades, revealing important roles in the survival of the fungus in hostile environments. The key genes and the encoded enzymes for pigment and melanin biosynthesis have recently been found in Ascomycota, including Aspergillus spp. In Aspergillus terreus, the pigmentation has remained mysterious with only one class of melanin biogenesis being found. In this study, we examined an intriguing, partially annotated gene cluster of A. terreus strain NIH2624, utilizing previously sequenced transcriptome and improved gene expression data of strain MUCL 38669, under the influence of a suggested quorum sensing inducing metabolite, butyrolactone I. The core polyketide synthase (PKS) gene of the cluster was predicted to be significantly longer on the basis of the obtained transcriptional data, and the surrounding cluster was positively regulated by butyrolactone I at the late growth phase of submerged culture, presumably during sporulation. Phylogenetic analysis of the extended PKS revealed remarkable similarity with a group of known pigments of Fusarium spp., indicating a similar function for this PKS. We present a hypothesis of this PKS cluster to biosynthesise a 1,8-dihydroxynaphthalene (DHN)-type of pigment during sporulation with the influence of butyrolactone I under submerged culture.

Transcriptomic Complexity of Aspergillus terreus Velvet Gene Family under the Influence of Butyrolactone I.

Filamentous fungi of the Ascomycota phylum are known to contain a family of conserved conidiation regulating proteins with distinctive velvet domains. In Aspergilli, this velvet family includes four proteins, VeA, VelB, VelC and VosA, and is involved in conidiation and secondary metabolism along with a global regulator LaeA. In A. terreus, the overexpression of LaeA has been observed to increase the biogenesis of the pharmaceutically-important secondary metabolite, lovastatin, while the role of the velvet family has not been studied. The secondary metabolism and conidiation of A. terreus have also been observed to be increased by butyrolactone I in a quorum-sensing manner. An enlightenment of the interplay of these regulators will give potential advancement to the industrial use of this fungus, as well as in resolving the pathogenic features. In this study, the Aspergillus terreus MUCL 38669 transcriptome was strand-specifically sequenced to enable an in-depth gene expression analysis to further investigate the transcriptional role of butyrolactone I in these processes. The sequenced transcriptome revealed intriguing properties of the velvet family transcripts, including the regulator laeA, and uncovered the velC gene in A. terreus. The reliability refining microarray gene expression analysis disclosed a positive regulatory role for butyrolactone I in laeA expression, as well as an influence on the expression of the canonical conidiation-regulating genes under submerged culture. All of this supports the suggested regulative role of butyrolactone I in A. terreus secondary metabolism, as well as conidiation.

Total laryngectomy: Surgical morbidity and outcomes - A case series.

BACKGROUND: Total laryngectomy (TL) is a well-established procedure for laryngeal and hypopharyngeal cancers. There is an increasing number of TLs done after organ preservation strategies. AIM: The aim of this study was to report 30-day morbidity and survival outcomes in patients undergoing TL at a tertiary referral center. SETTING AND DESIGN: This was a retrospective review of a prospective database of TL patients operated during 2012-2013. MATERIALS AND METHODS: Patient demographics and other data were captured from the database. Surgical complications were graded as per Clavien-Dindo grading system and were also divided into major and minor as per predecided criteria. Recurrence and survival data were computed using Kaplan-Meier survival curves. RESULTS: A total of 169 patients underwent TL during the study period. About 34% of the patients had received prior radiation therapy. Around 18% of the patients had major complications with a pharyngocutaneous fistula rate of 22.4%. Ninety percent of these were managed conservatively. Though used in a small subset, microvascular reconstruction had the least complication rates. The 3-year disease-free survival and overall survival were 66% and 72%, respectively. There was no difference in survival between per primum and salvage surgery cohorts. CONCLUSION: TL is a safe and oncologically sound procedure in patients with laryngeal and hypopharyngeal cancers. A large proportion of patients still undergo TL as a de novo procedure. This denotes that patients still present with locally advanced cancers which are not amenable to organ preservation.

Butyrolactone I Quantification from Lovastatin Producing Aspergillus terreus Using Tandem Mass Spectrometry-Evidence of Signalling Functions.

Aspergillus terreus is an industrially important filamentous fungus producing a wide spectrum of secondary metabolites, including lovastatin and itaconic acid. It also produces butyrolactone I which has shown potential as an antitumour agent. Additionally, butyrolactone I has been implicated to have a regulating role in the secondary metabolism and morphology of A. terreus. In this study, a quantitative time-course liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS-MS) analysis of butyrolactone I is reported for the first time in nine-day long submerged cultures of A. terreus. Butyrolactone I was fragmented in the mass analysis producing a reproducible fragmentation pattern of four main daughter ions (m/z 307, 331, 363 and 393) in all the samples tested. Supplementing the cultures with 100 nM butyrolactone I caused a statistically significant increase (up to two-fold) in its production, regardless of the growth stage but was constitutive when butyrolactone I was added at high cell density during the stationary phase. Furthermore, the extracellular butyrolactone I concentration peaked at 48 h post inoculation, showing a similar profile as has been reported for bacterial quorum sensing molecules. Taken together, the results support the idea of butyrolactone I as a quorum sensing molecule in A. terreus.

Application of fluorescent indicators to analyse intracellular calcium and morphology in filamentous fungi.

A novel staining and quantification method to investigate changes in intracellular calcium levels [Ca(2+)](i) and morphology in filamentous fungus is presented. Using a simple protocol, two fluorescent dyes, Fluo-4-AM and Cell trace calcein red-orange-AM were loaded into the filamentous fungus Penicillium chrysogenum. The present study investigates the applicability of using Ca(2+)-sensitive dye to quantify and image [Ca(2+)](i) in P. chrysogenum cultures chosen for its potential as an experimental system to study Ca(2+) signalling in elicited cultures. The dye loading was optimised and investigated at different pH loading conditions. It was observed that the fluorophore was taken up throughout the hyphae, retaining cell membrane integrity and no dye compartmentalisation within organelles was observed. From the fluorescent plate-reader studies a significant rise (p<0.001) in the relative fluorescence levels corresponding to [Ca(2+)](i) levels in the hyphae was observed when challenged with an elicitor (mannan oligosaccharide, 150mgL(-1)) which was dependent upon extracellular calcium. Concurrently a novel application of dye-loaded hyphae for morphological analysis was also examined using the imaging software Filament Tracer (Bitplane). Essential quantitative mycelial information including the length and diameter of the segments and number of branch points was obtained using this application based on the three-dimensional data.

Quorum sensing as a method for improving sclerotiorin production in Penicillium sclerotiorum.

Quorum sensing has been extensively studied in the bacterial kingdom but little is known about it in filamentous fungi. gamma-Butyrolactones have been established as quorum sensing molecules in Gram-negative bacteria (as acyl-homoserine lactones) and Gram-positive bacteria (as A-factor) and they are present in many filamentous fungi (e.g. as butyrolactone I in Aspergillus terreus). This study investigates possible role of multicolic acid (and related derivates) as quorum sensing molecule(s) in P. sclerotiorum and its effect on the production of secondary metabolite sclerotiorin. Exogenous addition of an ethyl acetate extract of supernatants from P. sclerotiorum IMI 104602 (Strain M) at 48 h of growth resulted in maximum sclerotiorin yield of 8.5 mg g(-1) in Strain M at 168 h post-inoculation, a 1.8-fold increase as compared to the control. Addition of spent medium containing gamma-butyrolactone molecules from this strain to P. sclerotiorum IMI 040574 (Strain S) resulted in 6.4-fold increase in sclerotiorin yield at 168 h post-inoculation without causing a significant change in the biomass production (p>0.05) or carbohydrate consumption rate (p>0.05). The results presented here suggest that multicolic acid (and related derivatives) function as quorum sensing molecules in the filamentous fungus P. sclerotiorum.

Microbial quorum sensing: a tool or a target for antimicrobial therapy?

Inter-cell communication aided by released chemical signals when cell density reaches a critical concentration has been investigated for over 30 years as quorum sensing. Originally discovered in Gram-negative bacteria, quorum-sensing systems have also been studied extensively in Gram-positive bacteria and dimorphic fungi. Microbial communities communicating via quorum sensing employ various chemical signals to supervise their surrounding environment, alter genetic expression and gain advantage over their competitors. These signals vary from acylhomoserine lactones to small modified or unmodified peptides to complex gamma-butyrolactone molecules. The scope of this review is to give an insight into some of the quorum-sensing systems now known and to explore their role in microbial physiology and development of pathogenesis. Particular attention will be dedicated to the signalling molecules involved in quorum-sensing-mediated processes and the potential shown by some of their natural and synthetic analogues in the treatment of infections triggered by quorum sensing.