Study of Maternal and Fetal Doppler Velocimetry, Histopathology of Placental Bed in Diabetic Pregnancy and Its Correlation to Fetal Outcome

Research | DOI: https://doi.org/10.31579/2642-9756/059

Study of Maternal and Fetal Doppler Velocimetry, Histopathology of Placental Bed in Diabetic Pregnancy and Its Correlation to Fetal Outcome

  • Emadeldin R. Matar 1*
  • Esmat Mahmoud 2
  • Mohammed H. Mostafa 3

Assistant Professor of Pathology, Faculty of Medicine, Al Azhar University. Egypt

*Corresponding Author: Emadeldin R. Matar, Assistant Professor of Pathology, Faculty of Medicine, Al Azhar University. Egypt

Citation: Emadeldin R. Matar, Esmat Mahmoud, Mohammed H. Mostafa (2021) Study of Maternal and Fetal Doppler Velocimetry, Histopathology of Placental Bed in Diabetic Pregnancy and Its Correlation to Fetal Outcome J.Women Health Care and Issues 4(3); DOI: 10.31579/2642-9756/059

Copyright: © 2021 Emadeldin R. Matar, this is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 19 April 2021 | Accepted: 26 April 2021 | Published: 05 May 2021

Keywords: fetal doppler velocimetry; diabetic pregnancy; fetal outcome

Abstract

Diabetes mellitus still represents an important medical problem during pregnancy, causing perinatal morbidity and mortality. Despite improved outcome reflected by a steep decline in perinatal mortality over the past few decades, controversy still exists regarding the care of the pregnant woman with both pre-existing and gestational Diabetes Mellitus. Doppler ultrasound is especially valuable during pregnancy because fetal maternal and placental circulations can be studied.
The aim of this work was to study the vascular changes in the uteroplacental and fetoplacental circulations, and to correlate these findings with histopathology of the placenta and placental bed, which may occur in association with diabetic pregnancies. The study was carried out on 100 pregnant women of comparable age and parity. They were divided into 2 groups. The control group comprising 20 normal non-diabetic pregnant women and the normotensive diabetic group comprising 80 pregnant diabetic women. All were singleton pregnancies of 34 weeks or more and were delivered by C.S the control and the study cases were subjected to history taking and thorough physical examination. They were also subjected to ultrasonographic examination for fetal biometric parameters and for Doppler examination. Doppler examination included umbilical artery, uterine arteries fetal middle cerebral artery. At the time of C.S the placenta and placental bed biopsy was obtained. After delivery, the Apgar score of the newborn was assessed at 1 and 5 minutes, the body weight was measured, and the fetus was followed up for any complications.
Result: There was a positive correlation between the umbilical artery PI and the mean blood glucose levels indicating that poor diabetic control is probably associated with increased umbilical artery PI. However, there was no significant difference between the mean value of the umbilical artery PI in the diabetic and control groups. The uterine arteries Doppler indices showed no significant findings between the diabetic and the control groups. Neither did the uterine arteries Doppler indices show a correlation with the mean blood glucose levels. There was no significant difference between the middle cerebral artery PI in the diabetic and control groups. This observation indicates that there was no redistribution in the fetal circulation in the fetuses of the diabetic group. There was also non correlation between the MCA Doppler indices and the glycemic control. Histopathologic studies of the placental bed showed marked difference between the diabetic group and the control group as regards lack of physiologic changes and arteriosclerotic changes, which emphasizes the effect of diabetes on the placental bed vasculature.
Conclusion: Abnormal umbilical artery waveform analysis is one of significant predictors of fetal compromise in diabetic pregnancy, but fetal compromise can occur in association with normal Doppler waveform analysis. In maternal diabetes the classic redistribution seen in fetal hypoxemia due to uteroplacental insufficiency may not occur in diabetic patient even in severely compromised fetuses. In maternal diabetes mellitus, maternal glycemic control has no effect on impedance to flow in the uterine and middle cerebral arteries. No relationship was found between the uterine or umbilical arteries Doppler indices and the placental bed decidual vascular pathology in diabetic pregnancies. There was no correlation between placental findings and the Doppler waveform analysis of the umbilical and the uterine arteries.

Introduction

Diabetes mellitus is a common medical condition sometimes complicating pregnant women. It is estimated that 1 out of every 200 pregnancies is complicated by progestational diabetes mellitus and additionally, that 5 in every 200 pregnant women will develop gestational diabetes [1].
Diabetic pregnancy is associated with increased perinatal morbidity and mortality due to congenital malformations, ‘unexplained’ intra – uterine fetal death and fetal macrosomia [2].
A recent method for antenatal fetal health assessment is the Doppler ultrasound which is used for hemodynamic assessment of maternal and fetal circulations [3].
Doppler ultrasound is a noninvasive method of studying the flow velocity within blood vessels, and especially valuable during pregnancy because fetal, maternal, and placental circulations can be studied [4].
The placenta of the diabetic women has attracted much interest because placental dysfunction is postulated as being partially responsible for the unduly high frequency of perinatal complications [5].
A great interest in studying uteroplacental vasculature has developed, as their lesions may be involved in the pathogenesis of placental insufficiency in pregnancies complicated by hypertension and diabetes [6].

Aim of the work

The aim of this work is to study vascular changes in fetal and placental circulations using ultrasound Doppler velocimetry and correlate it with placental and placental bed histopathological findings in diabetic pregnant females.
Patients and methods:
This study was carried out on 100 pregnant women admitted in the Obstetrics and Gynecology Department of Al Azhar University Hospitals, during the period from April 2019 to November 2020.
Case’s Selection
The patients were grouped into two groups as follow:
The Control Group (Normal Pregnancy):
This group consisted of 20 nondiabetic pregnant women.
Inclusion criteria

  • Singleton pregnancy.
  • Gestational age >34 weeks.
  • No obstetric complications.
  • No medical disorders.
  • Expected to be delivered by cesarean section (C.S) for example (contracted pelvis, previous 2 C.S).

The study group (diabetic pregnancy):
This group consisted of 80 diagnosed diabetic pregnant women, all types of diabetes were included, diabetic patients with type I, II and gestational diabetes.
Inclusion Criteria

  •           Singleton pregnancy.
  •           No congenital anomalies
  •           No history of chronic medical disease other than diabetes.
  •          All cases were expected to be delivered by C.S. For example (contracted pelvis, previous 2C.S).
  •          Gestational age ≥ 34 weeks.

All the patients in the study were subjected to the following:
Full history taking.
General and obstetric examinations.
Laboratory investigations:
Fasting and 2 hours postprandial blood glucose level, and mean blood glucose level estimated. Other investigations for antenatal care.
Sonographic examination:
The patients were subject to sonographic obstetric examination using Toshiba SSA 270 A for:
a) Fetal Biometry Biparietal diameter, femur length, abdominal circumference, and fetal weight.
b) Placental site and grading.
c) Amniotic fluid volume and aspect.
d) Assessment of any fetal anomalies.

Doppler Study:
Pulsed wave Doppler studies were performed on uterine, umbilical and middle cerebral arteries, the size of the sample volume was adapted to the vessel diameter to cover it entirely. All recordings used for measurements of fetal circulation were obtained in the absence of fetal body and breathing movements and at fetal heart rate of 120-160 beats/minute. The angle between the ultrasound beam and the direction of the flow in the vessels was always less than50˚.
All Doppler measurements were taken with 3 consecutive well-defined waveforms.

The UTERINE ARTERY DOPPLER (RIGHTAND LEFT UTERINE ARTERIES) e following vessels were studied:
The uterine velocity waveforms were obtained either vaginally or abdominally.
For vaginal studies:
Patient in supine position with her thighs abducted and knee flexed. The transducer (vaginal probe 7.5MHz) was placed into a sterile glove with coupling jelly and then introduced into the lateral vaginal fornix
For abdominal studies:
The abdominal studies were carried by placing the transducer (3.5 MHz) on the anterior abdominal wall in the right and left lower quadrants aimed into the lower uterine segment and gently moved around until the appropriate velocity waveforms are seen.
The main uterine artery was the target of study and the resistance index was the chosen measurement for analysis.
Fetoplacental Circulation: (Fetal Umbilical Artery)
The fetal umbilical artery was selected as a measurement for the fetal perfusion and blood supply of the fetal side of the placenta. It is measured by selecting one umbilical artery from a free loop of the umbilical cord [7].
 The pulsatility index of the umbilical artery was the chosen measurement for the analysis.

Fetal Middle Cerebral Artery
The standard plane was first obtained to measure the biparietal diameter. This plane included the thalamus and cavum of the septum pellucidum. Pulsations or flow of the middle cerebral artery could be seen at the level of the insula. The sample volume was placed over the middle cerebral artery and maximum flow velocity waveforms were recorded (8).
Histopathologic Studies
Placental Bed Biopsy
Placental bed biopsy was obtained at the time of Cesarean section under direct visualization of the placental site. The technique used was originally described by Robertson et al. (2016) [9]. After delivery of the baby, the site of the placenta was identified, and then the placenta was peeled away from its bed by the surgeon, while the site of the placenta was marked by the assistant by keeping a finger on the serosal surface opposite to the area specified. After delivery of the placenta, its site is checked by being somewhat depressed, focally disrupted and friable when compared with the smooth but undulating surrounding decidua parietals. This site was inspected for bleeding vessels, and a biopsy was taken using an ovum forceps or curved scissors. The biopsy was approximately one cm in diameter and half cm in depth including bleeding vessels whenever possible. A single hemostatic suture was inserted when needed. No problems were encountered with technique except that it was more difficult to perform when the placenta was anteriorly situated, but if the uterus was partially exteriorized and the upper lip of the lower segment incision is everted by the assistant, adequate access to the anterior placental site can be achieved.
The biopsy was fixed in formalin by placing it in 4% buffered neutral formaldehyde saline solution (the so called 10% formal saline). After 12 to 24 hours of primary fixation, the biopsy specimen can be cut into strips of about 3mm breadth, each strip being properly oriented in the ultimate wax block to yield perpendicular sections from the decidual surface to the myometrial base.
Conventional histopathological methods were used, and the paraffin sections stained with

  1. Hematoxylin and Eosin.
  2. Periodic acid Schiff technique (PAS)
  3. Verhoff Van Geison satin were used to study the spiral arteries

All the biopsies were examined histopathologically for:
1. Lack of physiologic changes.
2. Blood thrombi.
3. Interstitial hemorrhage.
4. Fibrinoid necrosis.
5. Elastosis and hyalinosis (Verhoff Van Geison)
6. Atherosis (Verhoff Van Geison)
7. Intimal thickening. (PAS)
8. Exaggerated cytotrophoblastic mitosis.
9. Endarteritis.
According to the degree of pathology, the diabetic group was further subdivided into: (Barth et al., 2017) (10).

  • Group I: normal decidual vasculature.
  • Group II: patients with blood thrombi, fibrinoid necrosis, atherosis or thickening.
  • Group III: patients with blood thrombi, fibriniod necrosis, atherosis or endarteritis.

Placental biopsy:
Each placenta with the cord and membranes was immersed in 10% formaline and left several days for fixation. This allows for easier handling and cutting of the placenta. Coronal sections being cut 1cm intervals and tissue samples were taken from a macroscopically normal central portion of the placenta avoiding the first 2cm form the margin [11]. This procedure was carried out without attempting to perform gross examination. Section of paraffin embedded tissues were stained with |

  1. Haematoxylin and Eosin,
  2. PAS and Verhoff Van Geison stain.

All sections were examined by the same pathologist without knowledge of the clinical history and blood flow results.

All the biopsies are examined histopathologically for:

                           1. Lack of physiologic changes.
                           2. Fibrin thrombi.
                           3. Blood thrombi.
                           4. Interstitial hemorrhage.
                           5. Fibrinoid necrosis.
                           6. Elastosis and hyalinosis (Verhoff Van Geison).
                           7. Atherosis (Verhoff Van Grison).
                           8. Intimal thickening. (PAS).
                           9. Calcification.
                         10. Infarcts.
                         11. Endarteritis.
                         12. Interstitial oedema.
                         13. Thickening of the villous membrane.

Assessment of the fetal outcome:

  1. Apgar score at one and five minutes.
  2. Careful examination for any evidence of congenital anomalies.
  3. Assessment of the fetal birth weight.

Statistical Analysis
All statistics were performed on an IBM compatible PC with Microsoft Excel spread sheet package version 9.0.

Results

There was a significant increase of blood glucose (fasting, 2h-pp and the mean) in the diabetic group compared to the control one, with no significant difference between them in the age and parity. No significant variation is detected regarding umbilical artery PI in both groups. No significant variation between rights, left and mean uterine arteries RI in both groups of the study (table 1, 2, 3).

Table (1): Clinical data of the control and study groups
Table (2): Comparison between the control and diabetic groups as regards the umbilical artery pulsatility index
Table (3): Comparison between the control and the diabetic groups as regards the right, left, and mean uterine arteries resistance index

No significant difference in cerebroumbilical ratio between the control and the diabetic groups. No significant variation as regards middle cerebral artery PI, in both groups of the study (table 4). 

Table (4): Comparison between the control and diabetic groups as regards the middle cerebral artery Pulsatility index and the cerebro /umbilical ratio 

The umbilical artery PI showed significant positive correlation with mean blood glucose. Neither the uterine arteries RI nor the middle cerebral artery PI showed significant correlation with mean blood glucose level in diabetic group (table 5).

Table (5): The correlation between Doppler parameters and the mean blood glucose level. 

There was significant difference between control and diabetic groups as regards histopathological changes of placental bed as lack of physiologic changes, blood thrombi, interstitial hemorrhage, fibrinoid necrosis, hyalinosis and mural thickening focal atherosis, intimal thickening, endarteritis, exaggerated cytotrophoblastic mitosis.No  significant difference between both groups as regards lack of physiologic changes,  but there is high significant elevation of different placental changes in diabetic group as thrombi (fibrin & blood), interstitial hemorrhage, fibrinoid necrosis, atherosis intimal thickening and interstitial oedema, also there is significant increase of hyalinosis ad mural thickening, calcification , infarcts, endarteritis and thickening of villous membrane (table 6).

Table (6): Comparison between the control and diabetic groups as regards the histopathologic criteria of placental bed and the placental biopsy.

In diabetic patients there was no significant difference between cases with positive and cases with negative lack of physiological changes in placental bed as regards mean blood glucose, umbilical PI, mean uterine RI, C/U ratio, fetal birth weight and Apgar score.   In diabetic patients there was no significant difference between cases with positive and cases with negative fibrin thrombi in placental biopsy as regards mean blood glucose, umbilical artery PI, mean uterine artery RI, fetal birth weight and Apgar score at 5 min. In diabetic patients there was no significant difference between cases with positive and cases with negative blood thrombi in placental biopsy as regards mean blood glucose, umbilical artery PI, mean uterine artery RI, fetal birth weight and Apgar score at 5 min. In diabetic patients there was no significant difference between cases with positive and cases with negative interstitial hemorrhage in placental biopsy as regards mean blood glucose, umbilical artery PI, mean uterine artery RI, fetal birth weight and Apgar score at 5 min. In diabetic patients there was no significant difference between cases with positive and cases with negative fibrinoid necrosis  in placental biopsy as regards mean blood glucose, umbilical artery PI , mean uterine artery RI, and Apgar Score at  5 min but fetal birth weight showed significant difference .In diabetic patients there was no significant difference between cases with positive and cases with negative hyalinosis and mural thickening in placental biopsy as regards mean blood glucose, umbilical artery PI, mean uterine artery RI, fetal birth weight and Apgar score 5 min. In diabetic patients there was no significant difference between cases with positive and cases with negative focal atherosis in placental biopsy as regards mean blood glucose, umbilical artery PI, mean uterine artery RI, fetal birth weight and Apgar score at 5 min. In diabetic patients there was no significant difference between cases with positive and cases with negative Intimal thickening in placental biopsy as regards mean blood glucose, umbilical artery PI, mean uterine artery RI, and Apgar score at 5 min but fetal birth weight showed significant difference .In diabetic patients there was no significant difference between cases with positive and cases with negative interstitial oedema in placental biopsy as regards mean blood glucose, umbilical artery PI, mean uterine artery RI, fetal birth weight and Apgar Score 5 min  (table 7).

.
.
.
.
Table (7):  Relation between the histopathologic criteria of placental bed and the placental biopsy other studied parameters in the diabetic group.
 

There was high significant difference as regards fetal birth weight and Apgar score at 1 and 5 minutes between both groups of the study (table 8).

Table (8): Comparison between the control and diabetic groups as regards fetal birth weight and Apgar Score 1 and 5 minutes.

Discussion

Diabetic pregnancy is associated with increased perinatal morbidity and mortality due to congenital malformations, ‘unexplained’ intra – uterine fetal death and fetal. macrosomia [12].
The placenta of the diabetic women has attracted much interest because placental dysfunction is postulated as being partially responsible for the unduly high frequency of perinatal complications [5].
This study was carried out on 100 pregnant women of comparable age and parity. They were divided into two groups, the control group comprising 20 normal non-diabetic women and the normotensive diabetic group comprising 80 pregnant diabetic women. There is significant difference between fasting blood sugar in the diabetic and control groups, but there is high significant difference between the two groups regarding 2h -post prandial. Blood sugar and mean blood sugar.

Doppler Study
Umbilical. Artery Doppler
In the present study, the umbilical. Artery pulsatility index (PI) showed no significant difference between the control and the diabetic patients (P> 0.05). The control group had a mean value of 0.98 (± 0.18) while the diabetic group had a mean of 1.16(± 0.58).
In accordance with our results Zimmermann et al. (2014), carried out serial. Measurements of impedance to flow in the umbilical. Artery in 53 women with insulin dependent diabetes and reported that, impedance was within the normal. Range of nondiabetic patients [13].

Uterine artery Doppler:
In the present study, the mean value for the RI in the control group was 0.49 (± 0.08) for the right uterine artery and 0.54 (± 0.12) for the left uterine artery, while that of the diabetic group was 0.48 ((± 0.11) for the right uterine artery and 0.49 (± 0.11) for the left uterine artery. Both groups showed no statistically significant difference between the two means (P> 0.05). The mean uterine artery RI for the control group was 0.51 (± 0.07) and that for the diabetic group was 0.48 (± 0.1) with no statistically significant difference (P > 0.05). Uterine artery flow velocimetry in normotensive diabetic pregnancies does not differ from normal pregnancies.
Mean uterine artery RI did not show significant correlation with the mean blood glucose level (r=0.21). This result indicated that, in the present study, there was no relationship between the uterine artery Doppler and the mean blood glucose in diabetic pregnancies.
Accordingly, the non-diabetic range of uterine artery Doppler waveform analysis was appropriate for normotensive diabetic pregnancies. According to our study, the uterine artery Doppler was not good predictor of adverse fetal outcome in normotensive diabetic pregnancies.
Grunewald et al. (2016) reported that in a study of 24 well controlled IDDM and 25 healthy pregnant women, there was no correlation between glycosylated hemoglobin and random blood sugar and PI values of the umbilical artery, uterine artery and fetal descending aorta. They also concluded that the normal. 3rd trimesters decline in utero-placental and fetal-placental pulsatility indices were absent in the diabetic group. The pulsatility index was not influenced by blood glucose regulation [14].

Middle Cerebral Artery Doppler (Mca)
In the present study, the PI of the control group showed a mean value of 1.85 (± 0.54) while that of the diabetic group was 1.92 (± 0.47) with no significant difference, indicating no evidence of arterial redistribution in normotensive diabetic pregnancy.

 The correlation coefficient between the middle cerebral artery PI and the mean blood glucose in the diabetic group was nonsignificant (r = 0.19 and P>0.05) which indicates that blood glucose level has no effect on the middle cerebral artery PI.
Changes in the RI of the cerebral artery appear to be more pronounced than those of the umbilical artery during pregnancy. IUGR, fetal distress, fetal hypertensive disease or toxemia have been associated with elevations in the PI, RI and S/D ratio in the umbilical artery, as well as a decrease in the PI, RI of the cerebral artery [15].
In agreement with our results, Ishimatsu et al. (2018), measured impedance to flow in the middle cerebral artery in 43 pregnant women with well- controlled diabetes mellitus at 24-38 weeks of gestation. The PI was within the normal range and was not significantly associated with maternal serum glucose, fructosamine or glycosylated hemoglobin level [16].
Leung et al. (2017), found that, Doppler study of the umbilical. Artery pulsatility index and middle cerebral artery pulsatility index was not useful in the prediction of Abnormal pregnancy outcome in GDM [17].

Cerebral Umbilical Ratio (Cur)
The cerebral umbilical index, which measures the proportion of flow supplying the brain and the placenta, is now the most powerful parameter for assessment of IUGR and hypoxia first, it takes into account the causes and consequences of the placental insufficiency responsible for IUGR and hypoxia. Second, it is not heart rate dependent. Third, it has a single cutoff value (CUR is normal. if it is > 1.0), at least during the second half of pregnancy. On the other hand, because IUGR is frequently associated with hypoxia, brain metabolic disturbances, and delayed brain development, the CUR, already an indicator of IUGR, is also and accurate parameter for the prediction of poor perinatal outcome. It is also clear that because the resistance indices are heart rate-dependent it is hazardous to draw any conclusion from a single value of any of these parameters. Only several. Successive daily measures of the Doppler indices can lead to a realistic evaluation of changes in cerebral hemodynamics. Moreover, any significant increase in the umbilical index or decrease in the cerebral or CUR index, even within the range, must be considered pathologic. Conversely, a progressive decrease in the umbilical and cerebral indices with a stable CUR, even outside normal limits, must be considered normal [18].
In this study there was no significant difference in the CUR between the diabetic and control groups. Also, there was no correlation between CUR and mean blood glucose level.
None of the control cases had a CUR value < 1>
Others studied 20 healthy women as a control group and 61patients with high-risk pregnancy that had Doppler assessment within two weeks of delivery. A cutoff value of 1.0 was selected to distinguish normal from abnormal C/U ratio values. At this cutoff value, sensitivity was 57.9% specificity was 75.6 % and the proportion of false positive results was 24.4 %. This study supported the well-known correlation between IUGR and abnormal fetal cerebral and umbilical velocimetry (19). This study also found a strong correlation between the C/U ratio and neonatal. Outcome. This study indicates that a normal C/U ratio even when obtained several weeks before delivery is a strong predictor of normal fetal outcome whereas an abnormal result is strongly associated with genetic abnormalities, increased cesarean section rates, perinatal mortality and severe neonatal morbidity, in both SGA and AGA fetuses. It was suggested that evaluation of the high-risk fetus with umbilical. Doppler alone is inadequate and that a better prognostic indicator may be obtained by processing both the umbilical and the cerebral circulations. However, this study is inadequate to determine the clinical usefulness of the C/U ratio (CUR) measurements in evaluation of the fetus at risk for IUGR   and neonatal morbidity. Such assessment requires the performance of a randomized clinical trial. [19]

Placental Bed
In this study, the placental bed biopsies showed that, in the control group, only 2 cases (10%) showed lack of physiologic changes in the intramyometrial. part of the spiral. arteries while in the diabetic group, 25 cases (31%) showed lack of physiologic changes in the intramyometrial. part of the spiral. arteries, 14 cases (18%) showed blood thrombi, 16 cases (20%) showed interstitial. hemorrhage, 14 cases (18%) showed fibrinoid necrosis, 26 cases (33%) showed hyalinosis and mural. thickening in the intramyometrial. part of the spiral. arteries, 14 cases (18 %) showed focal. atherosis, 15 cases (19%) showed intimal. thickening and 14 cases (18%) showed endarteritis.
In the diabetic group, there were 25 cases with lack of physiologic changes and 55 cases with normal physiologic changes. There was no significant difference in the umbilical artery PI, mean uterine artery RI, mean blood glucose level, CUR, fetal birth weight or Apgar score at 5 min between the two groups.
As regards lack of physiologic changes in the intramyometrial. Portion of the spiral arteries, it was previously reported in cases of hypertension with pregnancy and IUGR rather than in diabetic pregnancy [20].
It was found that in this study there was a significant difference in fetal birth weight (P < 0>
However, there was no significant difference in the mean uterine artery RI, umbilical artery PI or the mean blood glucose level between the 3 subgroups. This does not confirm a relationship between umbilicals. Or uterine Doppler indices and the decidual vascular pathology in normotensive diabetic pregnancies.
Against our results Barth et al. (2017), correlated Doppler indices from the uterine arcuate artery with the decidual vascular histology in patients with type I diabetes and confirmed a relationship between arcute artery Doppler indices and downstream decidual vascular pathology [10].

Placental Biopsy
In our study of the placental biopsies showed that, in the control group, 2 cases (10%) showed lack of physiologic changes, 2 cases (10%) showed fibrin thrombi, 1 case (5 %) showed hyalinosis and mural. thickening, 1 case (5%) showed calcification and 2 cases (10%) showed interstitial. oedema. In the diabetic group, 8 cases (10%) showed lack of physiologic changes, 32 cases (40 %) showed fibrin thrombi, 22 cases (27 %) showed blood thrombi, 25 cases (31 %) showed interstitial. hemorrhage, 37 cases (47%) showed fibrinoid necrosis, 26 cases (33%) showed intimal. thickening, 20 cases (25 %) showed calcification, 12 cases (15 %) showed endarteritis, 32 cases (40%) showed interstitial. oedema, and 14 cases (18%) showed thickening of the villous membrane. All these parameters showed statistical significances between the control group and diabetic group except lack of physiologic changes.
Correlating each item of pathological changes in placental biopsy in diabetics separately with mean blood glucose level, umbilical, uterine Doppler indices and Apgar score at 5 minutes. It was found no significant correlation between them.
It was found that there was a significant difference in the fetal. Birth weight in patients showing fibrinoid necrosis and intimal thickening (Table 18) in the placenta compared to those lacking these pathologic findings (P < 0>
In the present study, the percentage of vascular obliteration in the placental vessels was small, in the form of endarteritis, 12 cases (15%) and infarcts 12 cases (15 %).
In the present study it was also noted that there was a normal villous structure in 72 cases (90%) and only 14 cases (18%) showed thickening of the villous membrane. This might explain the presence of normal uteroplacental (uterine and umbilical), and fetal arterial Doppler indices in this study.
Bracero and associates (2015) studied 25 women with insulin-dependent diabetes in an effort to determine the underlying cause of abnormal umbilical artery Doppler velocimetry.  Placental morphology was evaluated and there were no statistically significant differences in placental. Weight, number of tertiary stem villi, number of small muscular arterial. Width, this study suggested that, the cause of abnormal Doppler results in pregnancies complicated by diabetes is a functional, rather than a structural placental process. [21]
Saldeen et al. (2019), studied umbilical artery Doppler, and segments from umbilical and uterine arteries examined histologically and incubated to determine prostacyclin / thromboxane synthesis ratio. They found that placental lesions are associated with lower prostanoid synthesis ratio in diabetes and impaired glucose tolerance compared with normal but not until structural signs of ischemia develop is a rise of umbilical artery blood flow resistance detected. [5]
Histological. Examination in 34- AGA and 24- LGA placentae of type I diabetic women and in 22- AGA and 16- LGA placentae of control women revealed several histological abnormalities as presence of nucleated fetal red blood cells, fibrinoid necrosis, villous immaturity that were observed more in diabetic placentae compared with control group. But placentae from LGA- nondiabetic women showed several similarities to those of women with diabetes [22].
Adverse Fetal Outcome
In this study there was high significant difference between control and study groups as regards the fetal birth weight, Apgar Score at one and five minutes and stay at incubator.
In this study, we defined adverse fetal outcome as delivery before 37 weeks, Apgar Score at 5 minutes < 7>
The first case was a noninsulin dependent diabetic patient of 5 years duration with fasting blood sugar 110 mg % and a two-hour glucose level of 167 mg % mean blood glucose level was 139 mg % umbilical. Artery PI was 0.80, right uterine artery RI was 0.45, left uterine artery RI was 0.52. The middle cerebral artery PI showed a value of 1.33 and cerebro umbilical ratio was 1.66. Cesarean section was performed at 37 weeks, to deliver a male 4 kg in weight. An Apgar score at 5 minutes was 7. He developed RDS and stay at incubator 7 days. The placenta and placental bed showed focal atherosis and intimal thickening of vessels.
The second case was an insulin dependent diabetic patient of 5 years duration with fasting blood sugar 104 mg% and two hours postprandial glucose level of 184 mg%. Mean blood glucose level was 144 mg% umbilical artery PI was 1.18, right uterine artery RI was 0.54, left uterine artery RI was 0.48. The middle cerebral artery PI showed a value of 2.6 and cerebro umbilical ratio was 2.25. Cesarean section was performed at 37 weeks, to deliver male 4 kg in weight. An Apgar score at 5 minutes was 7 and he developed RDS and stayed at incubator 5 days. The placenta and placental bed showed lack of physiologic changes, elastosis, and mural. Thickening and intimal thickening with thickening of the villous membrane.
The third case was an insulin dependent diabetic patient of 6 years duration with a fasting glucose level 140 mg % and a two-hour glucose level of 200 mg %. The mean blood glucose level was 170 mg % umbilical artery PI was 3.67 with reversal. In the diastolic blood flow waveform. Right uterine artery RI was 0.58, left uterine artery RI was 0.44, the middle cerebral artery PI was 2.27 and cerebro umbilical ratio was 0.62. Emergency Cesarean section was performed at 35 weeks and 4 days for fetal risk delivering a 3250-gm female with 5 minutes Apgar score was 6. The fetus died 48 hours later of RDS. The placenta showed fibrin thrombi, fibrinoid necrosis, intimal thickening, and interstitial oedema while placental bed showed interstitial hemorrhage, intimal thickening, and interstitial oedema.
The fourth case was an insulin dependent diabetic patient of 5 years duration with a fasting glucose level 104 mg % and a two-hour glucose level of 180 mg % mean glucose level was 142 mg. Umbilical artery PI was 1.03, right uterine artery RI was 0.56, left uterine artery RI was 0.62 and mean uterine RI was 0.59 middle cerebral artery PI was 1.69 and cerebro umbilical ratio was 0.61. Cesarean section was performed at 38 weeks and delivered a 4250-gm male with Apgar Score 6 at 5 minutes and stayed at incubator for 10 days for heart failure (which treated). The placenta showed fibrin thrombi and Fibrinoid necrosis while placental bed showed lack of physiological. Changes.   

Conclusion

  1. The non- diabetic range of uterine artery and MCA Doppler waveform analysis do not differ from that of diabetic pregnancies.
  2. Abnormal umbilical artery waveform analysis is one of significant predictors of fetal compromise in diabetic pregnancy, but fetal compromise can occur in association with normal Doppler waveform analysis.
  3. In maternal diabetes the classic redistribution seen in fetal hypoxemia due to uteroplacental insufficiency may not occur in diabetic patient even in severely compromised fetuses.
  4. In maternal diabetes mellitus, maternal glycemic control has no effect on impedance to flow in the uterine and middle cerebral arteries.
  5. No relationship was found between the uterine or umbilical arteries Doppler indices and the placental bed decidual vascular pathology in diabetic pregnancies.
  6. There is high incidence of decidual vascular pathologic changes associated with normotensive diabetic pregnancies.
  7. There is a poor correlation between the degree of glycemic control and pathological placental changes.
  8. There was no correlation between placental findings and the Doppler waveform analysis of the umbilical and the uterine arteries.

References

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

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Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

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Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

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Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

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Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

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Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

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Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

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Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

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Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

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Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

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Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

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Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

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Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

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Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

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Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

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Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

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Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

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Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

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Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

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Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

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Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

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Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

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Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

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Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

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Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

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S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

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Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

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Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

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Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

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Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

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Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

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Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

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Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

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Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

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Dr Susan Weiner

My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.

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Lin-Show Chin

My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.

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Sonila Qirko

My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.

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Luiz Sellmann