The effect of the different waves of COVID-19 pandemic on the outcome of diabetic foot ulcers.

AIMS: COVID-19 pandemic has massively impacted human health. We studied the effect of COVID-19 on outcome of Diabetic foot ulcers (DFUs). OBJECTIVES AND METHODS: We recruited 483 people with DFUs from June 2020 to April 2022 (pandemic) together with a matched group of 226 people with DFU from March 2019 to March 2020 (pre-pandemic). Primary endpoint was outcome of ulcers-healed or amputation (major/minor). It was sub-analysed into 3 waves of COVID-19. Secondary endpoint was healing of individual types of DFUs. Basic anthropometric data included site and type of ulcer (ischemic or neuropathic), duration, presence or absence of infection and Wagner's grading of DFUs was collected for all patients. Diagnosis of peripheral neuropathy was done by monofilament testing and peripheral arterial disease by handheld Doppler and ankle brachial index (ABI). Standardized treatment protocol was provided. All patients were monitored for 6 months. RESULTS: In the pandemic group 323 (66.9%) patients in whom ulcers healed, 70 (14.5%) underwent minor amputation, 11 (2.2%) major amputation, 29 (6%) were lost to follow up, 22 (4.6%) were not healed. Rate of healing of DFU was higher (66.9% vs 53.5%) and rate of amputation was lower (16.7% vs 23.4%) in the pandemic group than in the pre-pandemic group (P = 0.001 and 0.037 respectively). Rate of healing in first, second and third wave was 65.4%, 75.2%, 58.3% respectively (P = 0.001). Neuropathic ulcers though less prevalent (49.8% vs 57.8%) in the first two waves than in the third wave, healing was better (79.3% vs 75.6%) in the first two waves than in the third wave (P = 0.085 and 0.488 respectively). Similarly, amputation rates in ischemic and neuro-ischemic ulcers were greater in the third wave than first two waves (46.7% vs 15.7%, P = 0.049). CONCLUSION: During the COVID-19 pandemic, healing of neuropathic ulcers was better, especially in the first and second waves and travel restriction may have accounted for this. However, worsening of ischemic and neuro-ischemic ulcers was observed with more amputation in these two groups. Conversely, in the third wave withdrawal of lockdown led to worsening of DFUs resulting in less healing and more amputation.

Tumor microenvironment-induced tumor cell plasticity: relationship with hypoxic stress and impact on tumor resistance.

The role of tumor interaction with stromal components during carcinogenesis is crucial for the design of efficient cancer treatment approaches. It is widely admitted that tumor hypoxic stress is associated with tumor aggressiveness and thus impacts susceptibility and resistance to different types of treatments. Notable biological processes that hypoxia functions in include its regulation of tumor heterogeneity and plasticity. While hypoxia has been reported as a major player in tumor survival and dissemination regulation, the significance of hypoxia inducible factors in cancer stem cell development remains poorly understood. Several reports indicate that the emergence of cancer stem cells in addition to their phenotype and function within a hypoxic tumor microenvironment impacts cancer progression. In this respect, evidence showed that cancer stem cells are key elements of intratumoral heterogeneity and more importantly are responsible for tumor relapse and escape to treatments. This paper briefly reviews our current knowledge of the interaction between tumor hypoxic stress and its role in stemness acquisition and maintenance. Our review extensively covers the influence of hypoxia on the formation and maintenance of cancer stem cells and discusses the potential of targeting hypoxia-induced alterations in the expression and function of the so far known stem cell markers in cancer therapy approaches. We believe that a better and integrated understanding of the effect of hypoxia on stemness during carcinogenesis might lead to new strategies for exploiting hypoxia-associated pathways and their targeting in the clinical setting in order to overcome resistance mechanisms. More importantly, at the present time, efforts are oriented towards the design of innovative therapeutical approaches that specifically target cancer stem cells.

The collective impact of childhood abuse, psychache, and interpersonal needs on suicidal ideation among individuals with bipolar disorder: A discriminant analysis.

BACKGROUND: Suicide is one of the ten leading causes of death in the United States. Childhood abuse, psychache (intense emotional pain), and interpersonal needs are widely known to be associated with suicidal thoughts and behaviors. However, only a limited number of studies investigate whether these variables, when analyzed collectively, are able to distinguish between a group of individuals who report suicidal ideation and those who deny such thoughts. PARTICIPANTS AND SETTING: Data were collected from individuals (N =177) with a diagnosis of bipolar disorder participating in an intensive outpatient program that provides mental health care to indigent, mostly minority patients in Southeast United States. METHODS: The dependent variable was item number 9 on the Beck Depression Inventory that asks about any suicidal thoughts in the past two weeks. We utilized discriminant analysis to test whether childhood abuse, interpersonal needs, and psychache were collectively able to accurately identify group membership of the study participants. RESULTS: The discriminant model included six independent variables: three different types of childhood abuse (emotional, physical, and sexual), interpersonal needs (perceived burdensomeness and thwarted belongingness), and psychache. Results revealed that the model was able to correctly classify group membership in 75% of the individuals in the study. CONCLUSION: In context of bipolar disorder, history of childhood abuse (particularly sexual and emotional abuse), intense psychache, and greater perceived thwarted belongingness and burdensomeness put an individual at a higher risk of suicidal ideation. Gaining insight into the interactions among these variables may lead to formulating early interventions to prevent suicide in patients reporting this constellation of symptoms.

The effect of sulforaphane on perinatal hypoxic-ischemic brain injury in rats.

Perinatal hypoxic-ischemic insult (HII) is one of the main devastating causes of morbidity and mortality in newborns. HII induces brain injury which evolves to neurological sequelae later in life. Hypothermia is the only therapeutic approach available capable of diminishing brain impairment after HII. Finding a novel therapeutic method to reduce the severity of brain injury and its consequences is critical in neonatology. The present paper aimed to evaluate the effect of sulforaphane (SFN) pre-treatment on glucose metabolism, neurodegeneration, and functional outcome at the acute, sub-acute, and sub-chronic time intervals in the experimental model of perinatal hypoxic-ischemic insult in rats. To estimate the effect of SFN on brain glucose uptake we have performed 18F-deoxyglucose (FDG) microCT/PET. The activity of FDG was determined in the hippocampus and sensorimotor cortex. Neurodegeneration was assessed by histological analysis of Nissl-stained brain sections. To investigate functional outcomes a battery of behavioral tests was employed. We have shown that although SFN possesses a protective effect on glucose uptake in the ischemic hippocampus 24 h and 1 week after HII, no effect has been observed in the motor cortex. We have further shown that the ischemic hippocampal formation tends to be thinner in HIE and SFN treatment tends to reverse this pattern. We have observed subtle chronic movement deficit after HII detected by ladder rung walking test with no protective effect of SFN. SFN should be thus considered as a potent neuroprotective drug with the capability to interfere with pathophysiological processes triggered by perinatal hypoxic-ischemic insult.

Effectiveness of two tobacco cessation methods among TB patients.

BACKGROUND: Tobacco and TB are the world´s two greatest public health problems. Exposure to tobacco has been shown to be associated with higher risk of acquiring TB and adverse outcomes such as relapse and TB mortality.OBJECTIVE: To assess and compare self-reported tobacco quit status and biochemically verified cotinine levels among TB patients at different time intervals among two study groups.METHODS: A cluster, randomised controlled trial was conducted on TB patients attending DOTS centres in Delhi, India, who reported using tobacco in any form. Participants were assigned into one of two treatment groups. Centres were randomly assigned to two intervention groups: 1) integrated intervention using behavioural counselling with nicotine replacement therapy (NRT) gum, and 2) intervention using behavioural counselling alone (50 each in intervention and control group). The subjects were followed at Week 1, Month 1, Month 3 and Month 6 for tobacco cessation.RESULTS: At the end of 6 months, patients who received the integrated intervention had significantly higher rate of success in quitting tobacco than those who received the conventional TB treatment alone (78.7% vs. 57.8%; P < 0.03).CONCLUSION: DOTS with tobacco use dependence treatment was successful in our study in helping TB patients to quit tobacco dependence and should therefore be offered to every tobacco user.

Comparison of Mental Health Status of Married and Unmarried Girls of Late Adolescent Age in an Urban Slum of Delhi.

INTRODUCTION: Late adolescence age (16-19 years) is organized around central task of achieving an identity. In India, age at marriage for girls has been legally declared as 18 years, but many girls are married much before this age. Early marriage for girls can have profound psychological and emotional impacts. AIMS AND OBJECTIVES: The aim was to study the impact of marriage on mental health of married girls of late adolescent age and to compare them with unmarried girls of the same age. MATERIALS AND METHODS: A comparison study was conducted among girls of late adolescent age in an urban slum of North East Delhi. Background information was collected through oral questionnaire method. The mental health of the study participants was assessed using validated tool "General Health Questionnaire-12" and "Symptom Checklist-90." RESULTS: Education and economic status of participants and parents were significantly associated with early marriage. Majority of married girls were found to be associated with risk of developing mental health disorders.

Impact of red blood cell transfusions on intestinal barrier function in preterm infants.

OBJECTIVE: To determine the relationships of red blood cell (RBC) transfusion and enteral feeding to changes in intestinal permeability (IP) measured by the relative intestinal uptake of lactulose (La) and rhamnose (Rh) in preterm infants <33 wk gestation. DESIGN/METHODS: Infants 240-326wk gestation received La/Rh solution enterally on study days 1, 8 and 15.Urinary La/Rh ratio was measured by HPLC. Hematocrit preceding transfusion, total RBC transfusion volume, volume/kg, and feeding status during each study interval (birth-d1; d1-d8, and d8-d15) were determined. RESULTS: Of the seventeen (40.5%) subjects who received≥1 transfusion during the study period, 12 (70.6%) infants were <28 wk gestation and 5 (29.4%) infants were≥28 wk gestation, p < 0.0001. Lower pre-transfusion hematocrit was observed in intervals preceding high IP (La/Rh > 0.05) than in intervals preceding low IP (La/Rh≤0.05) measurements (33 vs 35.8, p = 0.1051). RBC transfusions occurred more frequently in intervals preceding high IP than in intervals preceding low IP (26.8%; vs 8.3%, p = 0.0275) with 5-fold higher total RBC volume and volume/kg in intervals preceding any time point with high IP. RBC transfusion during an interval was associated with a three-fold increased risk of high IP (aOR 2.7; 95% C.I 0.564-12.814; p = 0.2143). Exclusive breast milk exposure and post-menstrual age reduced the risk for high IP following RBC transfusion. CONCLUSIONS: Both RBC transfusion number and volume was associated with subsequent high IP measurements in preterm infants <33 weeks gestation and potentially may contribute to impairment of the preterm intestinal barrier.

An innovative way of managing coeliac artery stenosis during pancreaticoduodenectomy.

Coeliac artery stenosis (CAS) is rarely of consequence owing to rich collateral supply from the superior mesenteric artery via the pancreatic head. Pancreaticoduodenectomy (PD) in CAS disrupts these collaterals, and places the liver, stomach and spleen at risk of ischaemia. A 56-year-old man presented with a 3-week history of obstructive jaundice. Computed tomography revealed an operable periampullary tumour with CAS due to compression by the median arcuate ligament with multiple collaterals in the pancreatic head and a prominent gastroduodenal artery (GDA). Following unsuccessful coeliac axis endovascular stenting, a PD was performed. Intraoperative median arcuate ligament release failed to restore good flow in the common hepatic artery (CHA) and splenic artery (SpA) A decision was made to use the left gastric artery (LGA) for arterial reconstruction, disconnect it from the stomach with its origin intact and anastomose it to the supracoeliac aorta. Doppler ultrasonography with a GDA clamp confirmed good filling of the CHA and SpA via the LGA. The GDA was ligated and the PD completed. The patient had an uneventful recovery except for a biochemical pancreatic leak and was discharged on day 10. CAS during PD (confirmed by a decrease in CHA flow with a GDA clamp) requires an additional procedure to restore blood flow to the liver, stomach and spleen. Anastomosing the LGA to the supracoeliac aorta is a simple reconstruction technique for achieving this.

Indian childhood cirrhosis - down but not out: Report of a rare case with a practical clinicopathological diagnostic approach.

Indian childhood cirrhosis is an entity believed to be on the verge of extinction. We present the case of a 13-month-old girl presenting acutely with jaundice, fever, and persistently increasing bilirubin. Investigations revealed direct hyperbilirubinemia, elevated transaminases, anemia, a blood with few schistocytes, positive direct coombs test, and deranged prothrombin time. Viral, autoimmune, and metabolic workup was unremarkable. Ultrasonography showed chronic liver disease, portal hypertension, and ascites. Due to numerous confounding factors and a low index of suspicion, the diagnosis of Indian childhood cirrhosis remained elusive and was clinched only on liver biopsy, albeit more than three weeks later, shortly after which the child expired. The timing and technique of the liver biopsy may have profound impact on the ultimate clinical outcome. Close coordination between the clinical and pathological teams is essential for deciphering acute presentations where the etiology is uncertain. We highlight the clinical considerations, varied morphological pointers, and offer a diagnostic algorithm facilitating the consideration of this disease.

Low prevalence of Pneumocystis pneumonia in hospitalized patients with systemic lupus erythematosus: review of a clinical data warehouse.

Objective In the era of powerful immunosuppression, opportunistic infections are an increasing concern in systemic lupus erythematosus. One of the best-studied opportunistic infections is Pneumocystis pneumonia; however, the prevalence of Pneumocystis pneumonia in systemic lupus erythematosus is not clearly defined. This study evaluates the prevalence of Pneumocystis pneumonia in hospitalized systemic lupus erythematosus patients, with a focus on validating the Pneumocystis pneumonia and systemic lupus erythematosus diagnoses with clinical information. Methods This retrospective cohort study evaluates the prevalence of Pneumocystis pneumonia in all systemic lupus erythematosus patients treated at Columbia University Medical Center-New York Presbyterian Hospital between January 2000 and September 2014, using electronic medical record data. Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and patients with renal transplants (including both early and late post-transplant patients) represented immunocompromised control groups. Patients with systemic lupus erythematosus, Pneumocystis pneumonia, HIV/AIDS, or renal transplant were identified using diagnostic codes from the International Classification of Diseases, Ninth Revision (ICD-9). Results Out of 2013 hospitalized systemic lupus erythematosus patients, nine had presumed Pneumocystis pneumonia, yielding a low prevalence of Pneumocystis pneumonia in systemic lupus erythematosus of 0.45%. Three of the nine Pneumocystis pneumonia cases were patients with concomitant systemic lupus erythematosus and HIV/AIDS. Only one of these nine cases was histologically confirmed as Pneumocystis pneumonia, in a patient with concomitant systemic lupus erythematosus and HIV/AIDS and a CD4 count of 13 cells/mm3. The prevalence of Pneumocystis pneumonia in renal transplant patients and HIV/AIDS patients was 0.61% and 5.98%, respectively. Conclusion Given the reported high rate of adverse effects to trimethoprim-sulfamethoxazole in systemic lupus erythematosus and the low prevalence of Pneumocystis pneumonia in hospitalized systemic lupus erythematosus patients, our data do not substantiate the need for Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus patients, except in those with concurrent HIV/AIDS.

Effect of bone bank processing on bone mineral density, histomorphometry & biomechanical strength of retrieved femoral head.

BACKGROUND & OBJECTIVES: Standard processing of the bone grafts involves deep-freezing and sterilization with gamma irradiation which may alter mechanical properties of the bone graft. This study was aimed at measuring the effect of bone bank processing on the mechanical properties of bone allograft and its correlation with bone mineral density [BMD, dual-energy X-ray absorptiometry (DEXA Scan)] and histomorphometric indices. METHODS: Femoral heads retrieved from patients undergoing hip replacement surgeries were used as the material. Twenty femoral heads were under taken in the study. Each femoral head was cut into two equal cubes. One cube was subjected to BMD measurement using DEXA Scan followed by unilateral compression test. Histomorphometric indices such as trabecular number (Tb. N.), trabecular separation (Tb. S.), trabecular thickness (Tb. T.) and bone volume (B.V.) were calculated on the same specimen by a computer software. The other cube was kept in deep freezer (-76°C) for a minimum of three weeks, followed by gamma irradiation and subjected to similar tests. RESULTS: Results were compared in pre- and post-processed bone specimens. A significant loss of biomechanical strength (P<0.001) with mean a loss of 18.90 per cent was found in post-processed samples in uniaxial compression tests. Similarly, BMD (mean decrease by 13.8%, P<0.01) and histomorphometric indices such as Tb. T. (mean decrease by 12.37%, P<0.01), Tb. S. (mean increase by 12.60%, P<0.001) and B.V. (mean decrease by 20.84%, P<0.01) were found. However, Tb. N. was not significantly affected. INTERPRETATION & CONCLUSIONS: The current method of processing of bone allografts i.e. deep-freezing and gamma irradiation appeared to cause a significant reduction in the biomechanical strength of allogenic bone which was more suitable to be use in the morselized form. Appropriate consideration for decreased strength needs to be given when using allogenic bone graft as a structural graft.

Early Recognition of Fibrodysplasia Ossificans Progressiva-Important For the Clinician.

Fibrodysplasia ossificans progressiva is a rare disorder of heterotopic ossification. Procedures like biopsy and surgery are known to be aggravating factors in promoting heterotopic ossification Clues to clinical diagnosis may therefore be a great advantage to treating orthopedician. Valgus deformity of great toe is an important diagnostic clue for treating physicians and thus aids in preventing the clinicians from subjecting the patients to unnecessary invasive and traumatic procedures. Hence clinical clues to early diagnosis are important in establishing the correct diagnosis and directing future management.

Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II.

Mucopolysaccharidoses (MPS), a subgroup of lysosomal storage disorders, are caused due to deficiency of specific lysosomal enzyme involved in catabolism of glycosaminoglycans. To date more than 200 pathogenic variants in the alpha-l-iduronidase (IDUA) for MPS I and ∼500 pathogenic variants in the iduronate-2-sulphatase (IDS) for MPS II have been reported worldwide. The mutation spectrum of MPS type I and MPS type II disorders in Indian population is not characterized yet. In this study, we carried out clinical, biochemical, molecular and in silico analyses to establish the mutation spectrum of MPS I and MPS II in the Indian population. We conducted molecular analysis for 60 MPS-affected patients [MPS I (n = 30) (Hurler syndrome = 17, Hurler-Scheie syndrome = 13), and MPS II (n = 30) (severe = 18, attenuated = 12)] and identified a total of 44 [MPS I (n = 22) and MPS II (n = 22)] different pathogenic variants comprising missense, nonsense, frameshift, gross deletions and splice site variants. A total of 20 [MPS I (n = 14), and MPS II (n = 6)] novel pathogenic sequence variants were identified in our patient cohort. We found that 32% of pathogenic variants detected in IDUA were recurrent and 25% in MPS II. This is the first study revealing the mutation spectrum of MPS I and MPS II patients in the Indian population.

Optimised isolation of polysaccharides from Lentinula edodes strain NCBI JX915793 using response surface methodology and their antibacterial activities.

Mycelial growth in a defined medium by submerged fermentation is a rapid and alternative method for obtaining fungal biomass of consistent quality. Biomass, exopolysaccharides (EPS) and intracellular polysaccharides (IPS) production were optimised by response surface methodology in Lentinula edodes strain LeS (NCBI JX915793). The optimised conditions were pH 5.0, temperature 26°C, incubation period of 25 days and agitation rate of 52 r/min for L. edodes strain LeS. Under the calculated optimal culture conditions, biomass production (5.88 mg mL(-1)), EPS production (0.40 mg mL(-1)) and IPS production (12.45 mg g(-1)) were in agreement with the predicted values for biomass (5.93 mg mL(-1)), EPS (0.55 mg mL(-1)) and IPS production (12.64 mg g(-1)). Crude lentinan exhibited highest antibacterial effects followed by alcoholic, crude and aqueous extracts. The results obtained may be useful for highly effective yield of biomass and bioactive metabolites.

Cost-effectiveness of isoniazid preventive therapy for HIV-infected pregnant women in India.

BACKGROUND: India has a high burden of active tuberculosis (TB) and human immunodeficiency virus (HIV) infection. Pregnancy increases the risks of developing TB in HIV-infected women. Isoniazid preventive therapy (IPT) reduces progression to TB, but may increase costs and hepatotoxicity. The cost-effectiveness of IPT for HIV-infected pregnant women in India is unknown. DESIGN: We evaluated the cost-effectiveness of antepartum IPT among HIV-infected women in India using a decision-analytic model. We compared current practice (no IPT) with: Intervention 1 (IPT regardless of CD4 count) and Intervention 2 (IPT for those with CD4 count â©¿ 200 cells/µl). We modeled IPT irrespective of tuberculin skin test (TST) status and TST-driven strategies. Primary outcomes were anticipated costs, disability-adjusted life-years (DALYs) and TB cases. RESULTS: Both IPT interventions are highly cost-effective compared to no IPT at current willingness-to-pay thresholds (respectively US$178.00 and US$201.00 per DALY averted for Interventions 1 and 2). However, providing IPT irrespective of CD4 count results in the greatest health benefits (21 TB cases averted/1000 patients) compared to current practice. IPT irrespective of TST status was also highly cost-effective compared to TST-driven IPT (respectively US$1027.00 and US$1154.00/DALY averted for Interventions 1 and 2). CONCLUSION: Antepartum IPT for HIV-infected women is highly cost-effective for TB prevention compared to current practices in India.

Pyoderma gangrenosum in a renal transplant recipient: A case report and review of literature.

Pyoderma gangrenosum (PG) is a rare disorder of unknown etiology characterized by multiple cutaneous ulcers with mucopurulent or hemorrhagic exudate. This sterile neutrophilic dermatosis is known to occur in association with malignancy, infection, autoimmune disorders and drugs. Occurrence of PG in a renal transplant recipient, who is already on immunosuppressants, is rare. We hereby report a renal transplant recipient who developed PG 1-month after transplant and responded well to treatment with escalated dose of oral steroid.