Diabetes Technology in People with Type 2 Diabetes: Novel Indications.

PURPOSE OF REVIEW: Diabetes technology has been continuously evolving. Current versions of continuous glucose monitors (CGM) use minimally invasive designs, monitor glucose values with high accuracy, and can be used to guide insulin dosing. Extensive evidence supports the use of diabetes technology for monitoring and insulin administration in people with type 1 diabetes. However, there is emerging evidence for people with type 2 diabetes. In this review, we present the different technological devices used to monitor glucose and deliver insulin and the evidence supporting their use in people with type 2 diabetes. RECENT FINDINGS: The use of CGMs in people with type 2 diabetes treated with insulin or non-insulin therapies has been associated with improvements in glycemic control and time spent in hypoglycemia. Smart insulin pens and smart connected devices are options to track compliance and guide insulin delivery in people who do not require insulin pump therapy. Mechanical patch pumps can be used to reduce the burden of multiple daily insulin injections. Automated insulin delivery algorithms improve glycemic control without an increase in hypoglycemia. The use of technology in the management of type 2 diabetes generates glycemic data previously inaccessible, reduces barriers for insulin initiation, improves glycemic control, tracks adherence to therapy, and improves user satisfaction.

A study on the morbid histopathological changes in COVID-19 patients with or without comorbidities using minimally invasive tissue sampling.

COVID-19 causes morbid pathological changes in different organs including lungs, kidneys, liver, and so on, especially in those who succumb. Though clinical outcomes in those with comorbidities are known to be different from those without-not much is known about the differences at the histopathological level. To compare the morbid histopathological changes in COVID-19 patients between those who were immunocompromised (Gr 1), had a malignancy (Gr 2), or had cardiometabolic conditions (hypertension, diabetes, or coronary artery disease) (Gr 3), postmortem tissue sampling (minimally invasive tissue sampling [MITS]) was done from the lungs, kidney, heart, and liver using a biopsy gun within 2 hours of death. Routine (hematoxylin and eosin) and special staining (acid fast bacilli, silver methanamine, periodic acid schiff) was done besides immunohistochemistry. A total of 100 patients underwent MITS and data of 92 patients were included (immunocompromised: 27, malignancy: 18, cardiometabolic conditions: 71). In lung histopathology, capillary congestion was more in those with malignancy, while others like diffuse alveolar damage, microthrombi, pneumocyte hyperplasia, and so on, were equally distributed. In liver histopathology, architectural distortion was significantly different in immunocompromised; while steatosis, portal inflammation, Kupffer cell hypertrophy, and confluent necrosis were equally distributed. There was a trend towards higher acute tubular injury in those with cardiometabolic conditions as compared to the other groups. No significant histopathological difference in the heart was discerned. Certain histopathological features were markedly different in different groups (Gr 1, 2, and 3) of COVID-19 patients with fatal outcomes.

Lopinavir-Ritonavir in SARS-CoV-2 Infection and Drug-Drug Interactions with Cardioactive Medications.

Lopinavir-ritonavir combination is being used for the treatment of SARS-CoV-2 infection. A low dose of ritonavir is added to other protease inhibitors to take advantage of potent inhibition of cytochrome (CYP) P450 3A4, thereby significantly increasing the plasma concentration of coadministered lopinavir. Ritonavir also inhibits CYP2D6 and induces CYP2B6, CYP2C19, CYP2C9, and CYP1A2. This potent, time-dependent interference of major hepatic drug-metabolizing enzymes by ritonavir leads to several clinically important drug-drug interactions. A number of patients presenting with acute coronary syndrome and acute heart failure may have SARS-CoV-2 infection simultaneously. Lopinavir-ritonavir is added to their prescription of multiple cardiac medications leading to potential drug-drug interactions. Many cardiology, pulmonology, and intensivist physicians have never been exposed to clinical scenarios requiring co-prescription of cardiac and antiviral therapies. Therefore, it is essential to enumerate these drug-drug interactions, to avoid any serious drug toxicity, to consider alternate and safer drugs, and to ensure better patient care.

Cilnidipine loaded poly (ε-caprolactone) nanoparticles for enhanced oral delivery: optimization using DoE, physical characterization, pharmacokinetic, and pharmacodynamic evaluation.

Cilnidipine (CND), an anti-hypertensive drug, possesses low oral bioavailability due to its poor aqueous solubility, low dissolution rate, and high gut wall metabolism. In the present study, an attempt has been made to prepare CND loaded polycaprolactone based nanoparticles (CND-PCL-NPs) by nanoprecipitation method applying the concepts of Design of Experiments. Critical factors affecting particle size and loading efficiency (LE%) were assessed by a hybrid design approach, comprising of Mini Run Resolution IV design followed by Box-Behnken design. Particle size, PDI, zeta potential and LE% of optimized formulations of CND-PCL-NPs were 220.3 ± 2.6 nm, 0.25 ± 0.1, -19.5 ± 0.9 mV, and 46.4 ± 1.8%, respectively. No significant changes were observed in the physical stability of nanoparticles when stored at 25 °C/60% RH over a period of 3 months. Oral pharmacokinetic studies revealed that Fabs of CND-PCL-NPs (0.55) were significantly higher than the CND suspension (0.26). Pharmacodynamic studies have revealed that the mean percent reduction in systolic blood pressure (% ΔSBP) was significantly higher in the case of CND-PCL-NPs (42%) as compared to CND suspension (24%). Optimized CND-PCL-NPs offer great potential in providing higher and sustained antihypertensive effect compared to conventional formulations of CND.

Endocrine changes in SARS-CoV-2 patients and lessons from SARS-CoV.

Coronavirus infection outbreaks have occurred frequently in the last two decades and have led to significant mortality. Despite the focus on reducing mortality by preventing the spread of the virus, patients have died due to several other complications of the illness. The understanding of pathological mechanisms and their implications is continuously evolving. A number of symptoms occur in these patients due to the involvement of various endocrine glands. These clinical presentations went largely unnoticed during the first outbreak of severe acute respiratory syndrome (SARS) in 2002-2003. A few of these derangements continued during the convalescence phase and sometimes occurred after recovery. Similar pathological and biochemical changes are being reported with the novel coronavirus disease outbreak in 2020. In this review, we focus on these endocrine changes that have been reported in both SARS coronavirus and SARS coronavirus-2. As we battle the pandemic, it becomes imperative to address these underlying endocrine disturbances that are contributing towards or predicting mortality of these patients.

Efficiency of Mobile Video Sharing Application (WhatsApp®) in Live Field Image Transmission for Telepathology.

Telepathology is in its nascent stages in India. Video calling applications in mobile phones can be efficiently used to transmit static and live field microscopic images hastening low cost telepathology. To evaluate the efficiency of WhatsApp® Video Calling for dynamic microscopy in distant diagnosis. Thirty haematoxylin and eosin stained slides of common pathologies were retrieved from the archives of Department of Oral Pathology and Microbiology, coded with relevant history and given to three untrained investigators. The investigators then connected a mobile phone with VOIP facility to a microscope using a custom adaptor. Dynamic fields were transferred to three independent pathologists via WhatsApp® video call. The pathologists attempted to diagnose the lesion based on the live field video over their display screen (phone). Audio quality was found to be better than that of video. In 70% of the cases, pathologists could render a diagnosis (13% gave a confirmed diagnosis, 57.7% gave a probable diagnosis). The average time taken for connecting the adaptor, connecting the call to the pathologist and then receiving the diagnosis was 9:30 min. In addition, proper history taking and staining of the tissue slides were critical to arrive at the diagnosis. WhatsApp® free VOIP facility helped untrained investigators to send the live-field pathologic fields to a specialist rendering histopathological diagnosis. The factors affecting the diagnosis included network stability, clarity of images transmitted, staining quality and contrast of nuclear details of the stain. The history, clinico-pathologic correlation, transmission of static images, training of the person transmitting the images plays a vital role in rendering accurate diagnosis. Telepathology over WhatsApp® video calling could be used as an efficient screening tool to identify suspicious lesions and follow-up critical cases.

Soft tissue reactions following cochlear implantation.

INTRODUCTION: Cochlear implantation is a boon to children with hearing loss. Rarely, it can be associated with complications. Soft tissue reaction can be a particularly distressing complication. MATERIALS AND METHODS: The study was conducted on all patients presenting with soft tissue reaction post-cochlear implant in a tertiary care referral institute from March 2011 to June 2018. We graded the severity of soft tissue reaction as per the severity and then managed these patients accordingly. RESULTS: Thirty-five patients were included in this study. Grade 1 had 12 patients, grade 2 had 9, grade 3 had 4 and grade 4 had 9 patients. Grade 1, 2 and 3 reactions were managed conservatively, while grade 4 required surgery. The incidence of explantations increased with the grade severity. CONCLUSION: Soft tissue reaction post-cochlear implant is a rare, but distressing complication. Grading and analyzing them can help us manage them in a better way.

Profile of patients referred for lung transplant and their transplant-free survival.

INTRODUCTION: Lung transplant (LTx) is a potential treatment option for all patients with chronic, end-stage respiratory disease, who are refractory to optimal medical therapy or where no medical therapy exists. In India, LTx is still in its evolving stages and published literature is sparse. The current study was carried out to study the selection criteria for lung transplant and to evaluate the clinical and socio-economic profile of patients referred for the same at a tertiary health care facility. METHODS: The study was a descriptive, prospective, observational study. All adults referred for lung transplant were evaluated for clinical and laboratory profiles. All enrolled patients were assessed for presence of referral criteria, listing criteria, contraindications, and willingness for lung transplant. These patients were followed up for 2 years for transplant-free survival, and the Cox proportional hazards model was used to determine independent predictors of all-cause mortality. RESULTS: A total of 103 were included in study. The most common diagnosis was interstitial lung disease (57.2%), followed by bronchiectasis (17.5%) and COPD (13.6%). Most patients were referred for LTx at an advanced stage as 90% met listing criteria. Fifty-four (52.4%) patients had an absolute or relative contraindication to transplant; however, the majority of those contraindications were modifiable. Patients with a lower socio-economic status were less likely to be willing for LTx. The median survival was 757 days. A 6-minute walk distance (6MWD) lesser than 250 m was found to be an independent predictor of mortality. CONCLUSION: Making patients aware about lung transplant early in their treatment may give them sufficient time to come to terms with their disease and understand the risk and benefits associated. Efforts should be focused on screening and early treatment of reversible contraindications for the eligible patients. Patients with 6MWD < 250 m are at increased risk of mortality.

Conversion of phenols into selenophenols: seleno Newman-Kwart rearrangement.

A 'Se'lling point: The first thermally induced OAr →SeAr migration reaction is reported, and it can be used to prepare aryl selenols in three steps from the corresponding phenols. O-aryl selenocarbamates rearrange to Se-aryl carbamates via a four-membered transition state. The aryl selenols (isolated as the diselenides) can be prepared by hydrolysis of the Se-aryl selenocarbamates.

Serial Estimation of Serum Calcium and Ionic Calcium Level for Early Detection of Hypocalcemia After Total/Completion Thyroidectomy.

Hypocalcemia is an important and common complication following thyroid surgery. The development of postoperative hypocalcemia is likely to be multifactorial in nature. Patients with acute hypocalcemia may present with numbness of the distal extremities, circumoral paresthesia, and/or carpopedal spasm, laryngospasm, seizure and arrhythmias. In most cases, post-thyroidectomy hypocalcemia is temporary, but small percentage (0-12%) are permanent. The present study was a 1-year prospective interventional study conducted at tertiary care center, Jaipur, India. Total 42 patients who underwent thyroidectomy were included in study. Evaluation of Serum and Ionic Calcium Level done Preoperatively and Postoperative at 6, 12, 24 and 48 h and patients who develops hypocalcemia symptoms were recorded and data were analyzed. In our study hypocalcemia was seen in 13 (31%) out of 42 subjects. Ionic calcium in 'All patients' gradually decreased from pre operative 1.28 ± 0.04 mmol/l to 1.14 ± 0.08 mmol/l by 24 h. Highest incidence of hypocalcemia was seen in patients who had Total thyroidectomy + neck dissection (83.3%) compared to other type of thyroid surgery. we concluded that post thyroidectomy transient hypocalcemia is a frequent complication. Serial monitoring of calcium levels preoperatively and postoperatively combined with careful monitoring of signs and symptoms of hypocalcemia is an efficient and cost-effective tool to detect early post thyroidectomy hypocalcemia.

Chronic Pancreatitis Associated With a Variant of CFTR Gene Treated With Total Pancreatectomy and Autologous Islet Cell Transplantation.

Background/Objective: Total pancreatectomy is performed for pain relief in chronic pancreatitis. Concomitant autologous islet cell transplantation can be performed to improve glycemic control. We report the case of a patient with chronic pancreatitis who underwent a total pancreatectomy with autologous islet cell transplantation with increasing insulin requirements and its association with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder. Case Report: A 40-year-old woman presented with abdominal pain and had elevated levels of serum lipase. She was treated for acute pancreatitis. In the subsequent 2 years, she had 4 additional episodes of pancreatitis and eventually developed chronic abdominal pain. She underwent total pancreatectomy for pain relief with autologous intrahepatic islet cell transplantation. She experienced repeated episodes of pneumonia and underwent screening for cystic fibrosis, which showed a 7T/7T polymorphic variant at CFTR intron 8. The follow-up at 8 years after procedure showed increasing hemoglobin A1c levels despite increasing insulin use with multiple hospitalizations for hyperglycemia. The patient was transitioned to continuous subcutaneous insulin infusion with improvement in hemoglobin A1c levels. Discussion: Chronic pancreatitis can be a manifestation of an undiagnosed CFTR-related disorder, which in this case was followed by total pancreatectomy. Autologous islet cell transplantation was performed with declining postprocedural glycemic control. Interval failure of the transplanted islets is present in up to two thirds of the patients but is not affected by the presence of cystic fibrosis. Conclusion: A gradual decline in glycemic control may be expected in patients with autologous islet cell transplantation and can be improved with the use of continuous subcutaneous insulin infusion.

Effect of Rhinoplasty on Various Angles of Nose on Ideal Position and Alignment in Indian Population.

Study of anthropometric measurements of the nose makes possible a qualitative and quantitative analysis of surgical results. Analysis of pre- and post-operative changes in nasal tip projection, rotation and nasofrontal angle may also emphasize the fact of over correction or under correction of deformed nose to surgeon. Aim of our study to compare preoperative and postoperative nasal tip projection, rotation and nasofrontal angle after rhinoplasty. The present study was a 1.5 years prospective interventional study conducted at SMS Medical College, Jaipur, India from January 2021 to July 2022. Total 51 patients with external nasal deformity were included in our study. Pre-operative, immediate post-operative and 6 months follow-up nasofrontal, projection and nasolabial angle were recorded, compared and analyzed objectively. In our study significant improvements were observed in the nasolabial angle from 92.9 ± 16.4 to 101.6 ± 10.4 and 110.3 ± 9.8 and nasal tip projection from 0.74 ± 0.17 to 0.58 ± 0.11 and 0.52 ± 0.09 immediate post-op and at 6-months follow up respectively. Mean Nasofrontal angle at pre-op, intra-op and post-op 6 months was 132.5 ± 11.9, 135.4 ± 9.6 and 134.8 ± 9.4 and this difference was not found to be statistically significant. We would like to conclude that Indian noses which are predominantly small and shorter, our surgical procedure aimed at making them more prominent aesthetically on the face, so in the present study results were satisfactory in term of anthropometric parameter.

A Comparative Study of Surgical Outcomes in Children with Cochlear Implantation Using Posterior Tympanotomy & Modified Veria Technique.

Purpose: To compare the two common approaches of cochlear implantations i.e., mastoidectomy with posterior tympanotomy approach (MPTA) and modified veria technique and to know whether veria technique and its later modifications are as efficacious as the classic approach in terms of duration of procedure, gain in hearing and acquisition and incidence of complications if any. Methods: A prospective comparative study was undertaken at a tertiary care teaching institute. 30 children were selected and randomised into 2 groups who then underwent surgery from the same surgeon after proper evaluation but with 2 different approaches. Their outcomes were then observed and compared in terms of surgical technique and complications and hearing outcomes. Results: 30 children were operated with 15 in each group. In the study, patients under Group A (MPTA) had mean surgical duration of 139.67 ± 16.53 min while Group B (modified Veria) had of 84.67 ± 11.72 min, which was statistically significant (p < 0.05). 1 patient in Group A suffered House Brackman grade 4 facial nerve injury that recovered over 3 months and another had discolouration of the skin flap. No complications were observed in group B. During follow-up CAP and SIR scores were compared and were found to be statistically non-significant between the 2 groups (p value > 0.05), but the paired differences within each group showed statistical significance (P value- <0.001). Conclusion: Veria Technique (and its later modifications) for cochlear implantation is a simple, safe and easy procedure, which is as efficacious as MPTA with added benefits of consuming lesser surgical duration. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03399-1.

Classification of Seizure Termination Patterns using Deep Learning on intracranial EEG.

Seizure termination has received significantly less attention than initiation and propagation and consequently, remains a poorly understood phase of seizure evolution. Yet, its study may have a significant impact on the development of efficient interventional approaches, i.e., it may be critical for the design of treatments that induce or reproduce termination mechanisms that are triggered in self-terminating seizures. In this work, we aim to study temporal and spectral features of intracranial EEG (iEEG) during epileptic seizures to find time-frequency signatures that can predict the termination patterns. We propose a deep learning model for classification of multi channel iEEG epileptic seizure termination pattern into burst suppression and continuous bursting. We decompose the raw time series seizure data into time-frequency maps using Morlet Wavelet Transform. A Convolution Neural Network (CNN) is then trained on cross-patient time-frequency maps to classify the seizure termination patterns. For evaluation of classification performance, we compared the proposed method with k-Nearest Neighbour (k-NN). The CNN is shown to achieve an accuracy of 90 % and precision of 92 % as compared to 70% and 72% accuracy and precision achieved with the k-NN respectively. The proposed model is thus able to capture the temporal and spatial patterns which results in high performance of the classifier. This method of classification can be used to predict how a particular seizure will end and can potentially inform seizure management and treatment. Clinical relevance- This method establishes a model that can be used to classify seizure termination patterns with an accuracy of 90 % which can assist in better treatment of epilepsy patients.

Invasive Fungal Infections in Dengue Recovered Patients: A New Phenomenon in the Covid-19 Era.

Invasive fungal rhinosinusitis was seen to rise to epidemic levels after the 2nd wave of ongoing Covid pandemic, especially in tropical countries, maximally in India. A similar trend is being observed for cases who have recently recovered from dengue virus infection. Post dengue invasive fungal infection is a new presentation and any associations between it and Covid pandemic need to be studied in detail to help prepare for any complications. 3 patients presented to the out-patient department of E.N.T at a tertiary level teaching hospital in East India with complains similar to rhinosinusitis. These patients were then evaluated and diagnosed to be infected from Mucormycosis and Aspergillosis fungal sinusitis after which they were managed with surgical debridement and systemic antifungal therapy. All had a recent history of recovery from Dengue virus infection and a possible association could be suspected. 3 patients presented with complains of pain over upper jaw with orbital swelling and loss of vision developing over a period of 24 days. Two of them had ulceration of hard palate. They were then subjected to Contrast MRI along with CT scan of the Paranasal sinuses which depicted pansinus involvement with intracranial extension in two patients. These were then planned for diagnostic nasal endoscopies along with biopsies which turned out to be Invasive fungal sinusitis in the form of Aspergillosis and Mucormycosis. All the 3 patients had recent history of recovery from Dengue virus infection and did not have any other co-morbidities. Covid Associated Mucormycosis (CAM) is a well-known entity now but no reports of Dengue associated Invasive fungal sinusitis are yet reported. Whether this new phenomenon has anything to do with the interactions between dengue virus and coronavirus is not known at present and needs to be studied in detail so appropriate management protocols can be formulated.

Lateral Skull Base Lesions: Our Experience of 15 Years.

To analyse and report various aspects of lateral skull base surgery by describing the incidence and demographic variables, diagnostic and management challenges, surgical choices along with complications and their management and the long term morbidity and survival outcomes in our experience of 15 years. Retrospective review of complete records of all cases operated for lateral skull base tumors at a tertiary care teaching institution in India between timespan of 15 years from 2003 to 2018 was undertaken. 53 cases were selected and analysed. Those having follow up of less than 6 months were excluded. Outcomes were assessed in terms of incidence of types of tumors, benign or malignant, age and sex variation of the patients, staging status at presentation, status of facial and other lower cranial nerves pre-operatively, surgical techniques with complications if any, recurrences and survival. Of 35 benign tumors, tympanojugular paragangliomas were most common. Average age for these was 53 years with 19 females and 14 males. All were non-functional. Tinnitus and hearing loss were most common presentations. Class B2 and C1 tumors were most commonly encountered and the ITF A approach was most commonly used. Hearing loss and Facial palsy were commonest complication post-operatively. There were 2 recurrences. 18 malignancies were observed. Most were stage IV at presentation. Otorrhea and otalgia were most common presenting symptoms followed by hearing loss. 5 year survival was 55%. Successful treatment of lateral skull base lesions requires a multimodality therapy with team approach. Surgical resection is the primary management choice with variable approaches. ICA status related to the tumor is the most important consideration. Malignancies require more aggressive treatment for obtaining clear margins along with pre/post-op chemoradiation. Good results with acceptable complications can be obtained even with advanced tumors.

Risk factors for Coronavirus disease-associated mucormycosis.

BACKGROUND: The epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. We aimed to identify risk factors that may explain the burden of cases and help develop preventive strategies. METHODS: We performed a case-control study comparing cases diagnosed with CAM and taking controls as recovered COVID 19 patients who did not develop mucormycosis. Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Multivariate regression analysis was used to identify independent predictors. RESULTS: A total of 352 patients (152 cases and 200 controls) diagnosed with COVID-19 during April-May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean of 18.9 (SD 9.1) days after onset of COVID-19, and predominantly rhino-sinus and orbital involvement was present. All, but one, CAM cases had conventional risk factors of diabetes and steroid use. On multivariable regression, increased odds of CAM were associated with the presence of diabetes (adjusted OR 3.5, 95% CI 1.1-11), use of systemic steroids (aOR 7.7, 95% CI 2.4-24.7), prolonged use of cloth and surgical masks (vs. no mask, aOR 6.9, 95%CI 1.5-33.1), and repeated nasopharyngeal swab testing during the COVID-19 illness (aOR 1.6, 95% CI 1.2-2.2). Zinc therapy was found to be protective (aOR 0.05, 95%CI 0.01-0.19). Notably, the requirement of oxygen supplementation or hospitalization did not affect the risk of CAM. CONCLUSION: Judicious use of steroids and stringent glycemic control are vital to preventing mucormycosis. Use of clean masks, preference for N95 masks if available, and minimizing swab testing after the diagnosis of COVID-19 may further reduce the incidence of CAM.