Peripheral blood quantitation of CD26 positive leukemic stem cells as a predictor of tyrosine kinase inhibitor response in chronic myeloid leukemia.

INTRODUCTION: Leukemic stem cells (LSCs) are the transcriptionally low/silent cells which are resistant to the tyrosine kinase inhibitor. These have been found to play a pivotal role in disease relapse in chronic myeloid leukemia (CML) cases. The present study evaluated the correlation of absolute CML-LSC count in the peripheral blood (PB) at diagnosis and achievement of major molecular response (MMR) at 12 months in patients of CML-CP. METHODS: This was a prospective, observational, non-interventional single center study including newly diagnosed adult (>18 yrs) CML-CP patients. Absolute CD26 + CML-LSC quantification was done by multiparametric flow cytometry. Patients were treated with Imatinib treatment and subsequently monitored at 3-month intervals for BCR::ABL transcript levels. MMR was defined as a BCR::ABL1 transcript level of less than 0.1% on international scale. RESULTS: A total of 89 patients were enrolled in the study out of which 40.5% achieved MMR at 12 months. There was a significant difference in the median absolute CML-LSC count of the patients who achieved MMR at 12 months as compared to those who did not (58.5 vs 368.1 cells/µL; p value <0.001). Using a ROC analysis, a count of <165.69 CML LSC/µL was identified to have a sensitivity of 83.8% and specificity of 72.4%, in predicting the MMR at 12 months. CONCLUSION: Absolute CML-LSC count at diagnosis in the PB predicts the MMR achievement at 12 months. An absolute count of less than 165 cells/µL is highly predictive of achieving MMR at 12 months.

Masked alkynes for synthesis of threaded carbon chains.

Polyynes are chains of sp1 carbon atoms with alternating single and triple bonds. As they become longer, they evolve towards carbyne, the 1D allotrope of carbon, and they become increasingly unstable. It has been anticipated that long polyynes could be stabilized by supramolecular encapsulation, by threading them through macrocycles to form polyrotaxanes-but, until now, polyyne polyrotaxanes with many threaded macrocycles have been synthetically inaccessible. Here we show that masked alkynes, in which the C≡C triple bond is temporarily coordinated to cobalt, can be used to synthesize polyrotaxanes, up to the C68 [5]rotaxane with 34 contiguous triple bonds and four threaded macrocycles. This is the length regime at which the electronic properties of polyynes converge to those of carbyne. Cyclocarbons constitute a related family of molecular carbon allotropes, and cobalt-masked alkynes also provide a route to [3]catenanes and [5]catenanes built around cobalt complexes of cyclo[40]carbon and cyclo[80]carbon, respectively.

What If ? Pandemic policy-decision-support to guide a cost-benefit-optimised, country-specific response.

BACKGROUND: After 18 months of responding to the COVID-19 pandemic, there is still no agreement on the optimal combination of mitigation strategies. The efficacy and collateral damage of pandemic policies are dependent on constantly evolving viral epidemiology as well as the volatile distribution of socioeconomic and cultural factors. This study proposes a data-driven approach to quantify the efficacy of the type, duration, and stringency of COVID-19 mitigation policies in terms of transmission control and economic loss, personalised to individual countries. METHODS: We present What If…?, a deep learning pandemic-policy-decision-support algorithm simulating pandemic scenarios to guide and evaluate policy impact in real time. It leverages a uniquely diverse live global data-stream of socioeconomic, demographic, climatic, and epidemic trends on over a year of data (04/2020-06/2021) from 116 countries. The economic damage of the policies is also evaluated on the 29 higher income countries for which data is available. The efficacy and economic damage estimates are derived from two neural networks that infer respectively the daily R-value (RE) and unemployment rate (UER). Reinforcement learning then pits these models against each other to find the optimal policies minimising both RE and UER. FINDINGS: The models made high accuracy predictions of RE and UER (average mean squared errors of 0.043 [CI95: 0.042-0.044] and 4.473% [CI95: 2.619-6.326] respectively), which allow the computation of country-specific policy efficacy in terms of cost and benefit. In the 29 countries where economic information was available, the reinforcement learning agent suggested a policy mix that is predicted to outperform those implemented in reality by over 10-fold for RE reduction (0.250 versus 0.025) and at 28-fold less cost in terms of UER (1.595% versus 0.057%). CONCLUSION: These results show that deep learning has the potential to guide evidence-based understanding and implementation of public health policies.

A novel association of efavirenz induced severe cutaneous adverse reactions with HLA- DRB1*03:01: A case-control study from North-East India.

HIV-infected patients have a higher risk of developing cutaneous reactions to drugs than the general population. Severe cutaneous adverse reactions (SCARs) are not uncommon in patients taking antiretroviral therapy (HAART]. To evaluate HLA class I and II allele frequencies in HIV patients on HAART who develop SCARs due to nevirapine (NVP] or efavirenz (EFZ] containing regime and compare this genotype composition with HAART tolerant patients and healthy organ donors. A case-control study for 4 years was conducted with four subsets of patients hailing from north-east India:Cohort 1- HIV seropositive patients who developed SCARs due to EFZ (n = 8];Cohort 2 - HIV seropositive patients who developed SCARs due to NVP (n = 15]; Cohort 3 -HIV seropositive NVP/EFZ-tolerant patients (n = 18]; Cohort 4 - Healthy HIV seronegative organ donors (n = 169].Cohort 3 & 4 acted as control-group. These patients were genotyped for the HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1 by a sequence-based HLA typing method. HLA-DRB1*03:01 allele revealed a significant association with EFZ regimen-induced SCARs in 62.5% patients compared with only 5.56% observed in HAART-tolerant patients and 4.14% in healthy organ. HLA-B*3505was found to be significantly associated with NVP induced SCARs. We found significant novel association of HLA-DRB1*03:01 with EFZ induced SCARs in North-East Indian HIV patients. Thus, HLA-DRB*03:01 may be useful as a genetic marker to avoid EFZ induced serious cutaneous rashes. The molecular HLA characterization of these alleles may provide a novel insight into the immunological basis of the antiretroviral drug reactions.

Relevance of Posterior Gastric Vessel in Bariatric Surgery.

Posterior gastric vessel is commonly encountered (4-99%) during surgery of the stomach, spleen, and pancreas. Due to high variations in its origin, and course, it has not been unanimously described in literature. Its significance in bariatric surgery is largely neglected. We reviewed videos of 100 bariatric surgery cases done in our institute. This vessel was noted in 88 cases. We could identify the vessel in 54/63 LSG cases and all cases required division to free the fundus. It was identified in 34/37 RYGB cases. Thirty-one cases required lateralization while 3 cases required division due to more medial origin of the vessel. Its division or lateralization facilitates adequate mobilization of fundus to achieve the ideal configuration of sleeve in LSG and pouch in LRYGB.

o-Hydroxycinnamate for sequential photouncaging of two different functional groups and its application in releasing cosmeceuticals.

We demonstrated a new approach for the sequential photouncaging of two different functional groups from o-hydroxycinnamate. The second caged molecule initially remains in the locked state and is released only after attaining its unlocked state upon in situ generation of the second phototrigger, i.e., coumarin, thereby leading to the sequential release of alcohol and carboxylic acid. We have utilised the above strategy for the controlled release of cosmeceutical agents.

Laparoscopic management of epidermoid cyst in an unusual location.

The pararectal space or presacral space is a potential site for various cysts and tumours because it consists of many types of embryonic tissues. Although epidermoid cyst is a well-known entity, encountering a pararectal epidermoid cyst is relatively rare. The incidence of cystic tumours in the pararectal space has been reported to be 1 in 40 000 to 63 000 patients. Most of the tumours are asymptomatic and are incidentally discovered during routine imaging studies. Herein, we report a case of pararectal epidermoid cyst in a 51-year-old woman which was managed laparoscopically in a gastroenterology institute in South India.

Laparoscopic management of an unusual case of small bowel obstruction: appendiculoileal knotting.

Appendicitis presenting at small bowel obstruction due to the formation of encircling loop around a bowel segment is a rare occurrence. We report such case managed with the laparoscopic approach. A 45-year-old woman presented to emergency services with severe pain in abdomen and bilious vomiting in the past 2 days, having a history of abdominal hysterectomy 10 years ago. The abdominal examination was suggestive of bowel obstruction. A CT showed dilated bowel loops with complete cut-off at the level of the terminal ileum. The patient was taken for diagnostic laparoscopy. The inspection of the small bowel revealed an appendicular looping around the small bowel lumen. After separating, the appendix obstruction was relieved. Then, the tip of the appendix was dissected free from the parietal wall along with approximately 5 mL purulent fluid. Appendectomy was completed and based looped doubly using catgut endoloop. The patient had an uneventful recovery and was discharged on the second postoperative day.

Trigeminal hypoplasia due to vertebrobasilar dolichoectasia: A new entity.

The term "vertebrobasilar dolichoectasia" refers to anomalous dilatation of the intracranial arteries associated with elongation or tortuosity of the affected vessels. The etiology of the disease is unknown and is usually detected incidentally. The predominant clinical manifestations arise due to the mass effect of the dilated vessels and may include cranial nerve compression, extrinsic aqueductal compression, motor and sensory disturbances. Trigeminal hypoplasia is a very uncommon condition, usually described in association with Goldenhar-Gorlin syndrome and has not yet been attributed to vertebrobasilar dolichoectasia. The current case report highlights this rare association of trigeminal nerve hypoplasia and vertebrobasilar dolichoectasia, leading to hemifacial and corneal anesthesia.

Isolated crural hematoma mimicking retroperitoneal lymphadenopathy, a unique sign of traumatic diaphragmatic rupture: a case report.

Diaphragmatic injury following blunt thoracoabdominal trauma is rare and is usually associated with key radiological features like dependent viscera sign, collar sign, diaphragmatic thickening and defects. It may also be associated with secondary signs like intrathoracic herniation of abdominal viscera. Diaphragmatic crura, which are attached to the upper lumbar vertebra represent prominently thickened folds along the posterior diaphragm, are usually inconspicuous on routine Computed Tomography (CT) scans. We present a case of a young patient who sustained a motor vehicle accident and developed difficulty in breathing. CT scan of the patient revealed bilateral crural hematomas, with splenic and renal lacerations and no other sign of diaphragmatic injury. The patient was operated and blunt diaphragmatic rupture was confirmed at surgery.

Sonographic diagnosis of primary hydatid disease in the breast: the scroll sign.

Primary hydatid disease of breast is a rare entity and is caused by the larval stage of Echinococcus granulosus. The disease is more commonly seen in sheep-rearing populations and imaging plays a pivotal role in its diagnosis. Several imaging signs have been described in relation to hydatid cysts. However, the "scroll sign," due to the infolding of the endocyst, has rarely been encountered, with only one similar case in literature, in which the imaging findings were inconclusive. We present a case of primary hydatid disease of breast in a young Asian woman, with the sonographic scroll sign.

Sarcomatous transformation of osteochondroma of the coronoid process forming pseudoarthrosis with zygomatic arch mistaken for Jacob disease.

Osteochondromas are the most common benign osseous neoplasms, with a propensity to involve long bones. The involvement of the coronoid process is extremely rare, and osteochondromas of the coronoid process may form pseudoarticulations with the zygomatic arch when large, an entity that is extremely rare and termed as Jacob disease. Sarcomatous degeneration of osteochondroma of the coronoid process is an extremely rare entity and has not been described to date. Only 1 case of primary mesenchymal chondrosarcoma has been described. We present a case of a 24-year-old man with a chondrosarcoma of the coronoid process, who was wrongly diagnosed with Jacob disease on the basis of radiologic findings.

Role of ultrasonography in detection of renal artery pseudoaneurysm caused by retroperitoneal malignant peripheral nerve sheath tumor in a patient with neurofibromatosis type 1.

Malignant peripheral nerve sheath tumors (MPNSTs) are extremely uncommon neoplasms, predominantly seen within the deep soft tissues of the extremities, in close proximity to the nerve trunks. Retroperitoneal MPNSTs are exceedingly rare, usually seen in association with neurofibromatosis type 1 (NF-1), and often result from malignant degeneration of a plexiform neurofibroma. These tumors are highly malignant and the prognosis is worsened if they occur in association with NF-1. Metastasis is not uncommon, but local invasion by these tumors is rarely reported. Renal artery pseudoaneurysms are mostly iatrogenic and rarely result from invasion by retroperitoneal neoplasms. Ultrasonography is a valuable tool in early diagnosis of these neoplasms and vascular complications, particularly in emergency cases requiring immediate operative intervention. To the best of our knowledge, no case of renal artery pseudoaneurysm caused by retroperitoneal MPNST has been reported to date. We present a case of a middle-aged female with Von Recklinghausen disease, complaining of sudden onset of severe abdominal pain, where ultrasound accurately diagnosed renal artery pseudoaneurysm caused by a large retroperitoneal MPNST, and who was later treated by radical excision of the tumor and nephrectomy.