Nevin Manimala

Cardiol Young. 2021 May 10:1-5. doi: 10.1017/S1047951121001773. Online ahead of print.

ABSTRACT

BACKGROUND: Platelet indices are used to evaluate platelet activation and function which change in inflammatory diseases. We hypothesise that platelet indices such as plateletcrit, mean platelet volume, and platelet distribution width may be more useful as prognostic indicators for myopericarditis in children.

METHODS: A total of 60 children were included in this study. Group 1 consists of children with myopericarditis, Group 2 is those with respiratory infections, and Group 3 consists of control group children of similar age and gender with the patient groups. Complete blood count parameters, C-reactive protein, and troponin values of the whole study group were recorded. Myopericarditis was diagnosed based on acute chest pain, dyspnea, palpitations, heart failure signs, arrhythmia symptoms and ST/T wave change, low voltage, supraventricular tachycardia/ventricular tachycardia on ECG, or elevated troponin T/troponin I levels or functional abnormalities on echocardiography. A comparison of the platelet indices made during diagnosis and 2 weeks after treatment was done for the myopericarditis patients.

RESULTS: There was no statistically significant difference in platelet indicies values. However, the increase in platelets and plateletcrit values after the treatment of myopericarditis was statistically significant. This study pointed out that there was a negative correlation between platelet-plateletcrit values and the troponin I-C-reactive protein.

CONCLUSION: We found that platelet count and plateletcrit values increased after treatment. This is important as it is the first study in children to investigate the possible role of platelet indications for myopericarditis in children.

PMID:33966672 | DOI:10.1017/S1047951121001773

Int J Clin Pract. 2021 May 9:e14339. doi: 10.1111/ijcp.14339. Online ahead of print.

ABSTRACT

PURPOSE: We designed a multicenter, retrospective study to investigate the current trends in initial management of reflux with respect to European Association of Urology (EAU) Guidelines in Urology clinics of our country.

MATERIALS AND METHODS: The study group consisted of 1988 renal units (RU) of 1345 patients treated surgically due to vesicoureteral reflux (VUR) (between years 2003-2017 in 9 different institutions. Patients were divided into 2 groups according to time of initial treatment and also grouped according to risk factors by “EAU guidelines on VUR”.

RESULTS: In this series, 1426 RUs were treated initially conservatively and 562 RUs were initially treated with surgery. In initially surgically treated group, success rates of surgery decreased significantly in low and moderate risk groups after 2013 (p=0.046, p=0.0001, respectively), while success rates were not significantly different in high risk group (p=0.46). While 26.6% of patients in low risk group were initially surgically treated before 2013, this rate has increased to 34.6% after 2013, but the difference was not statistically significant (p=0.096). However, performing surgery as the initial treatment approach increased significantly in both moderate and high risk groups (p=0.000 and p=0.0001, respectively) after 2013. Overall success rates of endoscopic treatments and ureteroneocystostomy (UNC) operations were 65% and 92.9% before 2013, 60% and 78.5% after 2013, respectively. Thus, the overall success rate for surgery was 72.6%. There was significant difference between success rates of UNC operations before and after 2013(p=0.000), while the difference was not significant in the injection group (p=0.076).

CONCLUSION: Current trends in management of reflux in our country do not yet follow the EAU guidelines on VUR in low and moderate risk groups despite these reliable and accepted guidelines were expected to influence our daily approach.

PMID:33966353 | DOI:10.1111/ijcp.14339

Eur J Haematol. 2021 May 9. doi: 10.1111/ejh.13650. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to determine risk factors for development of acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM).

METHODS: We identified all patients diagnosed with MM in Sweden from January 1^st , 1958 to December 31^st , 2011. A total of 26,627 patients were diagnosed with MM with during the study period. Of these, 124 patients (0.5%) developed subsequent AML/MDS. For each patient with MM and a subsequent AML/MDS diagnosis, we randomly selected a matched (age, sex, and date of MM diagnosis) MM patient without a subsequent second malignancy diagnosis.

RESULTS: The cumulative melphalan exposure was significantly higher (OR=2.8, 95% CI 1.7-5.2; p<0.001) among cases (median 988 mg; IQR 644-1,640) compared to controls (median 578 mg; IQR 360-967). Median time to AML/MDS development was 3.8 years (IQR 2.8 – 5.8). Risk of AML/MDS was not statistically altered by M protein isotype, anemia, renal failure, hypercalcemia, lytic bone lesions, or radiation therapy.

CONCLUSION: In this nationwide population-based study, we show that increased cumulative doses of alkylating therapy with melphalan increases the subsequent risk of developing AML/MDS in patients with MM. Given improved survival in MM patients over the last decade future studies will be important to better define long-term risks.

PMID:33966293 | DOI:10.1111/ejh.13650

Mycoses. 2021 May 9. doi: 10.1111/myc.13301. Online ahead of print.

ABSTRACT

BACKGROUND: Recurrent and clinically unresponsive dermatophytosis is being increasingly observed in India. However, there is little information regarding the extent of the problem and the factors responsible for these difficult to treat superficial fungal infections.

AIM: To identify factors contributing to difficult to treat recurrent superficial fungal infections.

MATERIALS AND METHODS: This prospective cross-sectional study enrolled 105 patients of all age groups presenting with either recurrent or long-standing dermatophyte infection attending the out-patient department of Dermatology, Venerology and Leprosy of Bharati Hospital, Pune, India between September 2018 to March 2020. Patients were clinically examined, clinical history was taken, and questions were asked regarding their current complaints and recorded in a proforma. Data were analysed using the SPSS software package.

RESULTS: The males outnumbered females (74.3% vs 25.7 %). A strong association was observed between the presence of past history and duration of disease (p=0.007). The association of use of topical steroids or keratolytic agents with the duration of disease was statistically significant (p=0.022). There was a statistically significant inverse association of duration of disease with dermatologist consultation (p<0.001). The association between consultation with non-dermatologist and the duration of disease was statistically significant (p=0.035).

CONCLUSION: Hyperhidrosis, obesity, positive family history, tight clothing, and chronic diseases may be considered important factors in acquiring dermatophytic infection. However, when it comes to difficult to treat tinea infections, irrational usage of topical steroids, treatment from non-dermatologists, and a past history of tinea appear to be more critical causative factors. Treatment of dermatophytosis by dermatologists/ trained physicians and increasing general awareness of the public regarding the current situation about tinea in the country would help to alleviate the current crisis.

PMID:33966290 | DOI:10.1111/myc.13301

Med Phys. 2021 May 9. doi: 10.1002/mp.14936. Online ahead of print.

ABSTRACT

PURPOSE: Internal dosimetry has become a very important tool to evaluate the risks and benefits of new endoradiotherapeutic agents. Nowadays, some of the most successful targeted radionuclide therapy (TRT) agents are ¹⁷⁷ Lu-DOTA conjugates based on low molecular weight (LMW) Glu-ureido PSMA inhibitors. It has however been demonstrated that the DOTA chelating moiety reduces the internalization of the LMW-PSMA agent and its radiation dose to the tumour. Previously, we reported that ¹⁷⁷ Lu-scFvD2B, an antibody-based construct, demonstrated statistically significant higher cell uptake and internalization in LNCaP prostate cancer (PCa) cells (PSMA-positive) when compared to the LMW-PSMA agents ¹⁷⁷ Lu-PSMA-617 and ¹⁷⁷ Lu-iPSMA, two of the endoradiotherapeutic agents which currently are the most used in PCa therapy. The aim of this study is to estimate the preclinical ¹⁷⁷ Lu-scFvD2B organ and tumor-absorbed doses and to compare the values with those of ¹⁷⁷ Lu-PSMA-617 and ¹⁷⁷ Lu-iPSMA.

METHODS: ¹⁷⁷ Lu-scFvD2B, ¹⁷⁷ Lu-PSMA-617 and ¹⁷⁷ Lu-iPSMA were prepared and their radiochemical purity determined. Biodistribution studies of each radiopharmaceutical were then carried out in healthy mice to define the main source organs (SO) and to calculate the number of disintegrations in each source organs per unit of administered activity (N_SO ). Absorbed dose in the main organs were then calculated for each ¹⁷⁷ Lu-conjugate by means of OLINDA/EXM 2.1.1 software, using the calculated N_SO for both the adult male and the mouse phantoms as program inputs. Images of mice bearing micro-pulmonary tumors injected with ¹⁷⁷ Lu-conjugates were also obtained. Tumor standardized uptake values (SUV) for the different conjugates, obtained from the 3D SPECT image reconstruction of these mice, were used as the number of disintegrations in a tumor site per unit of administered activity (N_T ). The tumor-absorbed dose was calculated using the published electron dose S-values for sphere models with diameters ranging from 10 µm to 10 mm and considering a uniform activity distribution and tumor density equivalent to water density.

RESULTS: All ¹⁷⁷ Lu-labelled agents were obtained in high yield (98%). Dosimetric studies carried out using mouse phantoms demonstrated that organ absorbed doses of ¹⁷⁷ Lu-scFvD2B were from 1.4 to 2.3 times higher than those for ¹⁷⁷ Lu-iPSMA and from 1.5 to 2.6 times higher than those for ¹⁷⁷ Lu-PSMA-617. However, the ¹⁷⁷ Lu-scFvD2B values of tumor-absorbed doses for all investigated tumor sizes were from 2.8 to 3.0 times greater than those calculated for ¹⁷⁷ Lu-iPSMA and ¹⁷⁷ Lu-PSMA-617, respectively. Moreover, ¹⁷⁷ Lu-scFvD2B showed the highest tumor/kidney ratio when compared to those reported for ¹⁷⁷ Lu-albumin conjugates.

CONCLUSIONS: In this preclinical study, we demonstrated the potential of ¹⁷⁷ Lu-scFvD2B as a therapeutic agent for PSMA-expressing tumors, due to its higher tumor-absorbed dose when compared with ¹⁷⁷ Lu-LMW agents.

PMID:33966284 | DOI:10.1002/mp.14936

Adv Respir Med. 2021;89(2):145-157. doi: 10.5603/ARM.a2021.0037.

ABSTRACT

INTRODUCTION: There is increasing scientific interest in the possible association between hypovitaminosis D and the risk of SARS-CoV-2 infection severity and/or mortality.

OBJECTIVE: To conduct a metanalysis of the association between 25-hydroxyvitamin D (25(OH)D) concentration and SARS-CoV-2 infection severity or mortality.

MATERIAL AND METHODS: We searched PubMed, EMBASE, Google scholar and the Cochrane Database of Systematic Reviews for studies published between December 2019 and December 2020. Effect statistics were pooled using random effects models. The quality of included studies was assessed with the Newcastle-Ottawa Scale (NOS). Targeted outcomes: mortality and severity proportions in COVID-19 patients with 25(OH)D deficiency, defined as serum 25(OH)D < 50 nmol/L.

RESULTS: In the 23 studies included (n = 2692), the mean age was 60.8 (SD ± 15.9) years and 53.8% were men. Results suggested that vitamin 25(OH)D deficiency was associated with increased risk of severe SARS-CoV-2 disease (RR 2.00; 95% CI 1.47-2.71, 17 studies) and mortality (RR 2.45; 95% CI 1.24-4.84, 13 studies). Only 7/23 studies reported C-reactive protein values, all of which were > 10 mg/L. Conclusions 25(OH)D deficiency seems associated with increased SARS-CoV-2 infection severity and mortality. However, findings do not imply causality, and randomized controlled trials are required, and new studies should be designed to determine if decreased 25(OH)D is an epiphenomenon or consequence of the inflammatory process associated with severe forms of SARS-CoV-2. Meanwhile, the concentration of 25(OH)D could be considered as a negative acute phase reactant and a poor prognosis in COVID-19 infection.

PMID:33966262 | DOI:10.5603/ARM.a2021.0037

Adv Exp Med Biol. 2021;1269:283-288. doi: 10.1007/978-3-030-48238-1_45.

ABSTRACT

Hemorrhagic shock (HS) is a severe complication of traumatic brain injury (TBI) that doubles mortality due to severely compromised microvascular cerebral blood flow (mvCBF) and oxygen delivery reduction, as a result of hypotension. Volume expansion with resuscitation fluids (RF) for HS does not improve microvascular CBF (mvCBF); moreover, it aggravates brain edema. We showed that the addition of drag-reducing polymers (DRP) to crystalloid RF (lactated Ringer’s) significantly improves mvCBF, oxygen supply, and neuronal survival in rats suffering TBI+HS. Here, we compared the effects of colloid RF (Hetastarch) with DRP (HES-DRP) and without (HES). Fluid percussion TBI (1.5 ATA, 50 ms) was induced in rats and followed by controlled HS to a mean arterial pressure (MAP) of 40 mmHg. HES or HES-DRP was infused to restore MAP to 60 mmHg for 1 h (prehospital period), followed by blood reinfusion to a MAP of 70 mmHg (hospital period). In vivo two-photon microscopy was used to monitor cerebral microvascular blood flow, tissue hypoxia (NADH), and neuronal necrosis (i.v. propidium iodide) for 5 h after TBI+HS, followed by postmortem DiI vascular painting. Temperature, MAP, blood gases, and electrolytes were monitored. Statistical analyses were done using GraphPad Prism by Student’s t-test or Kolmogorov-Smirnov test, where appropriate. TBI+HS compromised mvCBF and tissue oxygen supply due to capillary microthrombosis. HES-DRP improved mvCBF and tissue oxygenation (p < 0.05) better than HES. The number of dead neurons in the HES-DRP was significantly less than in the HES group: 76.1 ± 8.9 vs. 178.5 ± 10.3 per 0.075 mm³ (P < 0.05). Postmortem visualization of painted vessels revealed vast microthrombosis in both hemispheres that were 33 ± 2% less in HES-DRP vs. HES (p < 0.05). Thus, resuscitation after TBI+HS using HES-DRP effectively restores mvCBF and reduces hypoxia, microthrombosis, and neuronal necrosis compared to HES. HES-DRP is more neuroprotective than lactated Ringer’s with DRP and requires an infusion of a smaller volume, which reduces the development of hypervolemia-induced brain edema.

PMID:33966231 | DOI:10.1007/978-3-030-48238-1_45

Adv Exp Med Biol. 2021;1269:235-239. doi: 10.1007/978-3-030-48238-1_37.

ABSTRACT

The aim was to evaluate the changes in brain tissue oxygenation, assessed by near-infrared spectroscopy (NIRS), during transcranial alternating current stimulation (tACS) in patients with mild and moderate traumatic brain injury (TBI). Nineteen patients with diffuse, blunt, non-severe TBI (mean age 32.7 ± 11.4 years; 4 women and 15 men; Glasgow Coma Score before tACS 14.1 ± 0.5) were treated by 10 Hz in-phase tACS applied for 30 minutes to the left and right lateral prefrontal cortex at 21 days after TBI. Regional cerebral tissue oxygen saturation (SctO₂) in the frontal lobes was measured simultaneously by the cerebral oximeter. Significance was preset to P < 0.05. The SctO₂ values before tACS were not different between hemispheres ~65%. After 15 minutes of tACS, a significant (p < 0.05) decrease in regional SctO₂ was observed with the minimum at the eighth minute of 53.4 ± 3.2% and 53.4 ± 3.2% in the left and right hemispheres, respectively. At the end of the stimulation (30 minutes), the hemispheric differences in cerebral oxygen saturation became statistically insignificant again (p > 0.05). Therefore, tACS causes a significant decrease in SctO₂, probably, due to neuronal activation. Our data indicate that tACS may need to be supplemented with oxygen therapy. Further research is required.

PMID:33966223 | DOI:10.1007/978-3-030-48238-1_37

Drug Saf. 2021 May 9. doi: 10.1007/s40264-021-01073-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Knowledge on the safety of medication use during pregnancy is often sparse. Pregnant women are generally excluded from clinical trials, and there is a dependence on post-marketing surveillance to identify teratogenic medications.

AIMS: This study aimed to identify signals of potentially teratogenic medications using EUROmediCAT registry data on medication exposure in pregnancies with a congenital anomaly, and to investigate the use of VigiBase reports of adverse events of medications in the evaluation of these signals.

METHODS: Signals of medication-congenital anomaly associations were identified in EUROmediCAT (21,636 congenital anomaly cases with 32,619 medication exposures), then investigated in a subset of VigiBase (45,749 cases and 165,121 exposures), by reviewing statistical reporting patterns and VigiBase case reports. Evidence from the literature and quantitative and qualitative aspects of both datasets were considered before recommending signals as warranting further independent investigation.

RESULTS: EUROmediCAT analysis identified 49 signals of medication-congenital anomaly associations. Incorporating investigation in VigiBase and the literature, these were categorised as follows: four non-specific medications; 11 likely due to maternal disease; 11 well-established teratogens; two reviewed in previous EUROmediCAT studies with limited additional evidence; and 13 with insufficient basis for recommending follow-up. Independent investigations are recommended for eight signals: pregnen (4) derivatives with limb reduction; nitrofuran derivatives with cleft palate and patent ductus arteriosus; salicylic acid and derivatives with atresia or stenosis of other parts of the small intestine and tetralogy of Fallot; carbamazepine with atrioventricular septal defect and severe congenital heart defect; and selective beta-2-adrenoreceptor agonists with posterior urethral valve and/or prune belly.

CONCLUSION: EUROmediCAT data should continue to be used for signal detection, accompanied by information from VigiBase and review of the existing literature to prioritise signals for further independent evaluation.

PMID:33966183 | DOI:10.1007/s40264-021-01073-z

Breast Cancer Res Treat. 2021 May 8. doi: 10.1007/s10549-021-06249-w. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the survival difference between limited axillary surgery and full axillary lymph node dissection (ALND) in patients with 1-3 positive sentinel lymph node biopsies (SLNBs) after neoadjuvant chemotherapy (NAC).

METHOD: We retrospectively analyzed data from 676 patients who underwent surgery between 2007 and 2017 with cT1-4, cN0-3, cM0 breast cancer at the time of diagnosis and 1-3 positive SLNBs after NAC. The patients received either SLNB only or completed level I or II ALND based on SLNB results. After propensity score matching, 483 patients who had undergone SLNB only (n = 188) and ALND (n = 295) were included. We examined overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival and compared them between the subgroups.

RESULT: At a median follow-up of 59.4 months, no significant statistical difference was observed in overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival between SLNB only and ALND. No significant differences were observed in the 5-year axillary recurrence-free survival (93.1% vs. 94.0%, hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.43-2.05, p = 0.876) and 5-year overall survival (97.7% vs. 97.3%, HR = 1.65, 95% CI = 0.58-4.65, p = 0.347) between the two groups.

CONCLUSION: Our analysis suggests that SLNB alone may be a possible option for patients with 1-3 sentinel node-positive breast cancer following NAC without significant compromise of recurrence or overall survival.

PMID:33966181 | DOI:10.1007/s10549-021-06249-w