Azithromycin resistance and its molecular characteristics in Neisseria gonorrhoeae isolates from a tertiary care centre in North India

Treatment guidelines for management of uncomplicated gonorrhoeae have been recently modified owing to alarming upsurge in azithromycin resistance. This study investigated the prevalence and genetic determinants of gonococcal azithromycin resistance in India. Four (5.7%) of 70 gonococcal isolates were resistant to azithromycin. Of 16 isolates investigated for molecular mechanisms of resistance, 13 (81.3%) and 6 (37.5%) isolates exhibited mutations in coding and promoter regions of mtrR gene, respectively. However, ermA, ermB and ermC genes or mutations in rrl gene were absent in all isolates. Azithromycin resistance is low in India posing no immediate threat to use of dual-therapy for syndromic management.     

Metformin therapy in COVID-19: inhibition of NETosis

Journal of Thrombosis and Thrombolysis -     

Deep Brain Stimulation Compared With Contingency Management for the Treatment of Cocaine Use Disorders: A Threshold and Cost-Effectiveness Analysis

ObjectivesCocaine is the second most frequently used illicit drug worldwide (after cannabis), and cocaine use disorder (CUD)-related deaths increased globally by 80% from 1990 to 2013. There is yet to be a regulatory-approved treatment. Emerging preclinical evidence indicates that deep brain stimulation (DBS) of the nucleus accumbens may be a therapeutic option. Prior to expanding the costly investigation of DBS for treatment of CUD, it is important to ensure societal cost-effectiveness.AimsWe conducted a threshold and cost-effectiveness analysis to determine the success rate at which DBS would be equivalent to contingency management (CM), recently identified as the most efficacious therapy for treatments of CUDs.Materials and MethodsQuality of life, efficacy, and safety parameters for CM were obtained from previous literature. Costs were calculated from a societal perspective. Our model predicted the utility benefit based on quality-adjusted life-years (QALYs) and incremental-cost-effectiveness ratio resulting from two treatments on a one-, two-, and five-year timeline.ResultsOn a one-year timeline, DBS would need to impart a success rate (ie, cocaine free) of 70% for it to yield the same utility benefit (0.492 QALYs per year) as CM. At no success rate would DBS be more cost-effective (incremental-cost-effectiveness ratio <$50,000) than CM during the first year. Nevertheless, as DBS costs are front loaded, DBS would need to achieve success rates of 74% and 51% for its cost-effectiveness to exceed that of CM over a two- and five-year period, respectively.ConclusionsWe find DBS would not be cost-effective in the short term (one year) but may be cost-effective in longer timelines. Since DBS holds promise to potentially be a cost-effective treatment for CUDs, future randomized controlled trials should be performed to assess its efficacy.     

Distinguishing between periampullary carcinoids and carcinomas--is this possible preoperatively?

It is difficult to distinguish between carcinoid tumors of the pancreatic head and periampullary region and carcinomas preoperatively. Between 1996 and 2002, 125 consecutive pancreaticoduodenectomies done by us for periampullary tumors (14 carcinoids, 111 carcinomas) were analyzed. Patients with carcinoid tumors had significantly younger mean age (48 vs. 54 years), longer history (32 vs. 8 weeks), lower serum total bilirubin levels (1.4 vs. 6.3 mg/dL) and on CT scan, had larger, well-localized tumors (5 cm vs. 2 cm). Their postoperative course was better with no mortality or major morbidity, whereas after resection for carcinoma 7 (6.3%) patients died and 30 (27%) had major postoperative complications. Thus, a tumor of this region in a young patient with indolent history, low bilirubin level and with CT scan depicting a large expansile lesion suggests a carcinoid. Such tumors may be safely resected with low postoperative morbidity and mortality and good long-term prognosis.     

Increased ratio of saturated to unsaturated C18 fatty acids in colonic adenocarcinoma: Implications for cryotherapy and lipid raft function

Mammalian fatty acid synthase (FASE) overexpression has been shown in a number of human malignancies including colonic adenocarcinoma. Since FASE synthesizes only saturated fatty acids, we hypothesized that cancer cells have a greater proportion of long-chain saturated fatty acids. We studied and found an unequivocal increase in saturated C18 fatty acid (stearic acid) in colonic adenocarcinoma compared to adjacent normal colonic mucosa. The increase is even more striking when measured as a ratio of stearic acid to the unsaturated C18 fatty acids (oleic acid and linoleic acid). This change in fatty acid composition of the cancer cells should significantly alter their physical and biological properties. The increase in relative proportion of saturated fatty acids should make the cancer cells more susceptible to cryodamage and measurement of fatty acid composition of cancer cells may help individualize the temperature for cryotherapy. Also, the lipid alterations may affect the structure and functions of lipid rafts, which may enable the cancer cells to affect signaling mechanisms such as those involved in cell growth and apoptosis. Dietary or therapeutic interventions targeting lipid rafts may thus be an option for cancer treatment.     

Effect of local mupirocin application on exit-site infection and peritonitis in an Indian peritoneal dialysis population.

BACKGROUND: Staphylococcus aureus-associated peritonitis and catheter exit-site infections (ESIs) are important causes of hospitalization and catheter loss in patients undergoing chronic peritoneal dialysis. Intranasal and topical use of mupirocin has been found to be an effective strategy in decreasing S. aureus-related infectious complications in persons who are carriers of S. aureus; however, there is no consensus regarding the prophylactic use of mupirocin irrespective of carrier status. We aimed to determine the potential effectiveness of application of mupirocin cream at the catheter exit site in preventing ESI and peritonitis irrespective of carrier status in a tropical country such as India. METHODS: This prospective historically controlled study was done in a total of 40 patients. From August 2003, all patients, incident and prevalent, were instructed to apply 2% mupirocin cream daily to the exit site instead of the older practice of povidone-iodine and gauze dressing. Patients were not screened to determine whether they were S. aureus carriers. The infection-related data for 1 year, until July 2004, were compared with the historical control, which was infection-related data for the year preceding the year of mupirocin application. RESULTS: Mean age of the study population was 62 years, with 61.8% being male and 64.3% being diabetic. Local application of mupirocin led to a significant reduction in the incidence density per patient-month of both ESI and peritonitis compared to controls (0.15 vs 0.37 and 0.37 vs 0.67, p = 0.01 for both). This amounted to a relative reduction of 60.5% and 55% respectively. ESI and peritonitis due to S. aureus were also significantly lower in the study group compared to controls (incidence density per patient-month 0.05 vs 0.13 and zero vs 0.17 respectively, p < 0.01 for both). There occurred no catheter removal due to infection-related complications during the study period compared to two during the control period. None of the patients reported a mupirocin-related adverse effect. CONCLUSIONS: Daily application of mupirocin at the exit site is a well-tolerated and effective strategy in reducing the incidence of ESI and peritonitis in a tropical country such as India. It can thus significantly reduce morbidity, catheter loss, and transfer to hemodialysis in peritoneal dialysis patients.     

Ehlers-Danlos syndrome – vascular type (ecchymotic variant): cutaneous and dermatopathologic features

Ehlers-Danlos syndrome – vascular type, the only lethal form, is rarely reported in dermatology literature. It is characterized by translucent, atrophic skin, easy bruising, arterial, intestinal and/or uterine fragility manifesting as varicose veins, aneurysms and vascular/visceral/uterine rupture. As its dermatopathologic features are not well elucidated, diagnosis is often made after a catastrophic complication or at autopsy. This 36 year-old non-consanguineous male had brown-black plaques with atrophy and frequent ulceration over legs and dorsal feet and tortuous varicose veins around ankles for the past 15 years. Perivenous skin was translucent and hypopigmented. He had multiple and ecchymotic keloids and small atrophic, pityriasis versicolor-like lesions over trunk. He did not have hypermobile/hyperextensible skin and joints and showed no systemic or investigative abnormality. Histopathologic features of atrophic lesion included blood extravasation in atrophic epidermis/dermis, focal clustering and dilatation of blood vessels, malformed vessel walls, abundant hemosiderin in the dermis and homogenously stained/whorled patterned collagen especially around blood vessels. Pathology of keloidal lesion showed new collagen and vascular fragility. These histopathologic features appear of diagnostic value especially in patients who have compatible clinical findings but cannot afford confirmation by biochemical testing for abnormal synthesis of type III procollagen or identification of mutations in the COL3A1 gene.     

Exacerbation of Partial Seizures and Onset of Nonepileptic Myoclonus with Carbamazepine

A child had two to three generalized tonic-clonic (GTC) seizures per week unresponsive to phenobarbital (PB) and valproate (VPA). Interictal EEG demonstrated left occipital spikes. When carbamazepine (CBZ) therapy was started, he developed very frequent (4-6/day) complex partial seizures (CPS) characterized on ictal EEG by focal right temporal lobe discharges. The seizure exacerbation, which was associated with development of nonepileptic, multifocal myoclonus, resolved 24 h after CBZ was discontinued. The exacerbation occurred with therapeutic CBZ serum levels, but may have been related to the toxic levels of carbamazepine-10, 11-epoxide (CBZE).     

CT appearances of hydatid disease at various locations

Hydatid disease has characteristic imaging features on CT, which allow accurate preoperative diagnosis in most cases. However, when it occurs at unusual locations the diagnosis is often difficult, especially as the imaging appearance varies at different sites. In this article we have presented a pictorial review of the CT features of disease due to Echinococcus granulosus at various sites in the human body.