The endocrinology of the urinary bladder.

The urinary bladder primarily functions as a reservoir for urine. Apparently, it serves only a mechanical and passive role in the urinary tract, but closer scrutiny reveals that it has several meaningful endocrine interactions. This vital organ has an intricate plexus of neurons that release neurohormones concerned with the functioning of the bladder. Endocrine disorders, most notably diabetes, can cause a broad spectrum of bladder dysfunction. The current review explores the bladder as a source of neurotransmitters, a target for organ damage due to uncontrolled endocrinopathy, a beneficiary of hormonal therapy, and a tool to improve endocrine health.

Fitterfly Diabetes CGM Digital Therapeutics Program for Glycemic Control and Weight Management in People With Type 2 Diabetes Mellitus: Real-world Effectiveness Evaluation.

BACKGROUND: Digital therapeutic platforms facilitate health care through patient-centered strategies based on multidisciplinary teams and shared decision-making. Such platforms can be used for developing a dynamic model of diabetes care delivery, which can help in improving glycemic control by promoting long-term behavior changes in people with diabetes. OBJECTIVE: This study aims to evaluate the real-world effectiveness of the Fitterfly Diabetes CGM digital therapeutics program for improving glycemic control in people with type 2 diabetes mellitus (T2DM) after the completion of 90 days in the program. METHODS: We analyzed deidentified data of 109 participants in the Fitterfly Diabetes CGM program. This program was delivered through the Fitterfly mobile app coupled with continuous glucose monitoring (CGM) technology. This program consists of 3 phases: the first phase is observation, wherein the patient's CGM readings are observed for 7 days (week 1); the second phase is the intervention; and the third phase aims at sustaining the lifestyle modification introduced during the second phase. The primary outcome of our study was the change in the participants' hemoglobin A1c (HbA1c) levels after program completion. We also evaluated the changes in participant weight and BMI after the program, changes in the CGM metrics in the initial 2 weeks of the program, and the effects of participant engagement in the program on improving their clinical outcomes. RESULTS: At the end of the 90 days of the program, the mean HbA1c levels, weight, and BMI of the participants were significantly reduced by 1.2% (SD 1.6%), 2.05 (SD 2.84) kg, and 0.74 (SD 1.02) kg/m2 from baseline values of 8.4% (SD 1.7%), 74.45 (SD 14.96) kg, and 27.44 (SD 4.69) kg/m2 in week 1, respectively (P<.001). The average blood glucose levels and time above range values showed a significant mean reduction by 16.44 (SD 32.05) mg/dL and 8.7% (SD 17.1%) in week 2 from week 1 baseline values of 152.90 (SD 51.63) mg/dL and 36.7% (SD 28.4%), respectively (P<.001 for both). Time in range values significantly improved by 7.1% (SD 16.7%) from a baseline value of 57.5% (SD 25%) in week 1 (P<.001). Of all the participants, 46.9% (50/109) showed HbA1c reduction ≥1% and 38.5% (42/109) showed weight loss ≥4%. The average number of times the mobile app was opened by each participant during the program was 108.80 (SD 127.91) times. CONCLUSIONS: Our study shows that participants in the Fitterfly Diabetes CGM program showed a significant improvement in their glycemic control and reduction in weight and BMI. They also showed a high level of engagement with the program. Weight reduction was significantly associated with higher participant engagement with the program. Thus, this digital therapeutic program can be considered as an effective tool for improving glycemic control in people with T2DM.

Personalized glycemic response led digital therapeutics program improves time in range in a period of 14 days.

Background: Lifestyle modification is an integral aspect for the management of type 2 diabetes (T2D). However, it is difficult to ensure the accuracy of personalized lifestyle advice. The study aims to analyse the real-world effectiveness of personalized glycemic response based Diabefly-Pro digital therapeutics for better glycemic control. Methods: Data from continuous glucose monitoring (CGM) of 64 participants with T2D was analysed. All participants were provided with modified lifestyle plan based on their personalized glycemic response. The CGM data was analysed for a period of 7 days, before and after the introduction of modified lifestyle plan. Primary outcome of the study was change in time in range (TIR). Secondary outcomes of the study were change in mean blood glucose, time above range (TAR), time below range (TBR) and glucose management indicator (GMI). Results: Significant improvement in glycemic control was observed after the introduction of personalized lifestyle plan. Median reduction in mean blood glucose was from 139.5 (118.3 to 169.3) mg/dL to 122.0 (101.5 to 148.8) mg/dL (p < 0.0001). TIR and GMI improved from 70.50 (50.75 to 83.50) % to 75.00 (58.25 to 89.00) % (p = 0.0001) and 6.64 (6.13 to 7.35) % to 6.23 (5.74 to 6.86) % (p < 0.0001) respectively. TAR reduced significantly from 17.00 (4.25 to 38.0) % to 6.00 (1.25 to 26.0) % (p < 0.0001). No significant increase in TBR was observed (p = 0.198). Conclusion: Personalized glycemic response-based Diabefly-Pro digital therapeutics program was effective in achieving better glycemic control in people with T2D.

Video Call-based Fitness Assessment shows Poor Fitness in People with Type II Diabetes: Findings from Diabefly Digital Therapeutics Program.

OBJECTIVE: Exercise and physical activity are integral aspects for the effective management of diabetes. Unsupervised home exercise although very accessible is limited by poor adherence, risk of injury, and a higher dropout rate of participants. A fitness assessment by a qualified physiotherapist can help in understanding the baseline fitness of individuals and thus generating appropriate exercise prescriptions. The current study assesses the feasibility of video call-based fitness assessment for people with diabetes. The study also assesses the effect of current physical activity status and pain on performance in physical fitness tests. METHODS: One hundred participants with type II diabetes (T2D) underwent 6-minute walk test (6MWT), 1-minute push-up test, wall sit test, 1-minute sit-up test, and V-sit and reach test for measuring different components of physical fitness such as aerobic capacity, upper body strength, lower body strength, core strength, and flexibility, respectively. The performance in physical fitness of participants was analyzed after the video consult along with pain complaints and current exercise status. RESULTS: All the participants underwent the physical fitness test safely based on video call. Out of all the participants, a good range score was achieved by 52% in 6MWT, 17% in push-up test, 1% in wall sit test, 6% in sit-up test, and 9% in V-sit and reach test. Current physical activity status (aerobic exercise for minimum 20 minutes) did not show any association with performance in fitness tests (p = 0.89 for push-up test, p = 0.50 for wall sit test, p = 0.23 for sit-up test, and p = 0.10 for V-sit and reach test). Presence of upper body and lower body pain affected the performance in push-up test and wall sit test with 71.4% and 95.6% of participants achieving scores in poor to below-average range (p-value < 0.001). CONCLUSION: The study showed the safety and feasibility of conducting video call-based assessment of physical fitness by physiotherapists. The study also highlighted the poor glycemic control, high cardiovascular risk, and poor level of physical fitness in people with diabetes in India. Insights based on physical fitness, current physical activity status, and pain can help in developing personalized exercise plans for people with diabetes.

Prediabetes: A Pragmatic approach to counselling and coaching.

Prediabetes is often considered as the link between normoglycaemia and diabetes. Though a lot of emphasis is given to an individual after the development of diabetes, pre-diabetes is often not adequately addressed in clinical practice. Given a distinct diagnostic criterion, its association with metabolic complications, an opportunity to prevent further progression to diabetes and the large number of people affected with it, makes it a subject of great importance and opportunity. In this brief manuscript we compare and contrast prediabetes with diabetes mellitus. We also describe a pragmatic approach to address a patient with prediabetes.

What's in a Name? Redefining Type 2 Diabetes Remission.

Diabetes remission is a concept that is marked by ample attention, but lack of unanimity. This opinion piece explores existing definitions of diabetes remission and proposes a contemporary and comprehensive framework to help define this clinical state. Type 2 diabetes remission is defined as a healthy clinical state characterized by achievement of HBA1c below the targeted level, maintained for at least 6 months, with or without continued use of lifestyle modification and/or metformin, provided that this is not due to complications, comorbid conditions or concomitant therapy.Diabetes Remission: Infographic.

Abdominoscrotal Lymphangioma Masquerading as a Communicating Hydrocele: A Case Report.

A 5-year old boy presented with a picture of communicating hydrocele and was discovered to have an abdominoscrotal lymphangioma after undergoing hydrocele surgery. Upon initial presentation the lymphangioma was missed and the child underwent inguinal approach surgery for hydrocele. The lymphangioma was then noticed as an abdominal lump due to a rapid increase in size within 1 week following the hydrocele surgery. The sudden enlargement of the lymphangioma was due to intra-cystic hemorrhage post-operatively. The lymphangioma was then completely excised with no recurrence noted after 1 year of follow up. This is a rare case of a retroperitoneal, abdominoscrotal lymphangioma masquerading as a communicating hydrocele. Keywords: Communicating Hydrocele, Abdominoscrotal lymphangioma, Scrotal Swelling.

Stage 4S Neuroblastoma: A Report of Two Cases Presenting with Extremes of Biological Behavior.

Neuroblastoma is the most common extracranial solid tumor in childhood. Stage 4S is a special stage of neuroblastoma in which majority of cases may have spontaneous regression; however, in some cases the tumor is rapidly progressive with poor prognosis and thus requires aggressive therapy. Dilemmas in its management and therapy will be discussed. We report two cases of stage 4S neuroblastoma exemplifying these two extreme behaviors. The first case is of a four-month-old baby who initially presented with a thigh lump, labial and foot nodules as well as hepatic and adrenal involvement. Following the confirmation of stage 4S Neuroblastoma with favorable histology and N-MYC negative amplification, a watchful observation approach was elected. Currently, the patient has completed two years of uneventful follow-ups with normal development. The second case is of a full-term new born baby who presented with abdominal distention and respiratory distress. Stage 4S Neuroblastoma was confirmed with an unfavorable histology and metastasis to the liver and the left adrenal gland. Due to the deterioration of the patient's condition, chemotherapy with carboplatin and etoposide was initiated for six cycles with a good and rapid response. The patient completed two years of follow up without recurrence.

Anogenital distance is determined during early gestation in humans.

STUDY QUESTION: Does cord blood androgen level obtained at birth affect the AGD in human newborns? SUMMARY ANSWER: In human newborns, though males have a significantly longer AGD compared to females (as early as 22 weeks of gestation) the AGD is not affected by androgen levels at birth in both the sexes. WHAT IS KNOWN ALREADY: Animal studies have reported a critical time period in early fetal life, termed the masculinization programming window (MPW) during which AGD is fixed by in utero androgen action and is unaffected by testosterone levels later during gestation. Thus, AGD may serve as a lifelong biomarker of androgen exposure during this window. This MPW is hypothesized to occur in humans at 8-14 weeks of gestation during which AGD is fixed. The effect of androgens (testosterone) on AGD after the MPW in humans is not known. Furthermore, altered AGD has been associated with various human reproductive health disorders in both males and females. STUDY DESIGN, SIZE, DURATION: A prospective descriptive cohort study was performed using data from randomly selected neonates (n = 205) born at a single center over a period of 1 year (August 2015 to August 2016). PARTICIPANTS/MATERIALS, SETTING, METHODS: AGDs in male (n = 117) and female infants (n = 88) together with penile width, glans girth and stretched penile length were measured by trained caregivers. Gestation ranged from 22 to 41 weeks and infants were examined within 24 h of birth (within 48-72 h in very sick preterm infants after clinical stabilization). AGD-1 was measured from the center of the anus to the posterior base of scrotum in males or to the posterior fourchette in females. AGD-2 was measured from the center of the anus to the anterior base of the penis in males or to the clitoris in females. Sex steroid hormones (testosterone, 17-OH progesterone (17-OHP) and androstenedione) were measured in serum prepared from umbilical cord blood samples taken at birth, using liquid chromatography-tandem mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: Males had a significantly lower gestational age (mean ± SD; 34.6 ± 4.9 versus 36.1 ± 4.1 weeks, P = 0.04), and a significantly longer AGD-1 (mean ± SD; 21.6 ± 6.0 versus 12.7 ± 3.8 mm, P < 0.001) and AGD-2 (41.9 ± 8.7 versus 33.9 ± 7.1 mm, P = 0.004) compared to female infants, respectively. The cord serum testosterone levels were significantly higher for male than female infants [median, interquartile range; 13.0 (7.3, 20.5) versus 4.1 (2.5, 5.9), ng/dl, P < 0.001]. There was no difference in levels of 17-OHP (P = 0.697) or androstenedione (P = 0.601) between the two sexes. On multiple regression analysis after adjusting for potential confounders, none of the AGD's in both males and females correlated with any sex steroid hormonal levels. We also provide normative charts for penile length, penile width and glans girth in preterm and term infants. LIMITATIONS, REASONS FOR CAUTION: No data were collected on family history of genital malformation, infertility or hormonal disorders, parental endocrine-disrupting chemical exposure or diet pattern, any of which might have influenced the AGD and/or sex steroid hormone levels in the offspring. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that AGD in humans, like animals, is fixed in early gestation (likely during the hypothesized MPW) and is unaffected by androgen levels thereafter. Thus, AGD can serve as a biomarker of in utero androgen action during early gestation (likely 8-14 weeks) in humans. As such, causes of human newborn and adult reproductive health disorders, such as endocrine disruptors, should be explored during early gestation. However, further larger studies are needed to help corroborate these findings. STUDY FUNDING/COMPETING INTERESTS: No specific funding was obtained for this study, and all authors have no conflict of interest to declare.

Shorter anogenital distance correlates with the severity of hypospadias in pre-pubertal boys.

STUDY QUESTION: Do pre-pubertal boys with hypospadias have a shorter anogenital distance (AGD) than boys with normal genitalia? SUMMARY ANSWER: AGD is significantly shorter in boys with hypospadias and decreases with the severity of hypospadias. WHAT IS KNOWN ALREADY: Animal studies have shown that androgen disruption and exposure to endocrine disrupting chemicals during a critical time period in early gestation, termed the male programming window (MPW), result in hypospadias and reduced AGD; and the severity of hypospadias correlates with the reduction in AGD. However, this correlation has not been established in humans. STUDY DESIGN, SIZE, DURATION: A prospective descriptive study involving measurement of AGD in pre-pubertal boys (n = 458) presenting to our pediatric urology clinic with hypospadias and normal genitalia was performed over a period of 3 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: AGD was measured in pre-pubertal boys from 5 months to 14 years of age presenting to our clinic with hypospadias (n = 180: four were excluded) and compared with randomly selected boys with normal genitalia (controls, n = 274). Three variants of AGD, from the midpoint of the anus to base of the scrotum (AGD-AS), to the anterior base of penis (AGD-1) and to the posterior base of penis (AGD-2), were measured and assessed for correlation with the severity of hypospadias. Severity of hypospadias was classified as anterior, middle and posterior according to the meatal location. MAIN RESULTS AND THE ROLE OF CHANCE: No significant difference in weight (P = 0.123), age (P = 0.162) or height (P = 0.591) between the two groups was observed. Only AGD-AS was significantly shorter in boys with hypospadias compared with controls (mean ± SD: 40.6 ± 9.7 mm versus 45.6 ± 9.4 mm, P < 0.001). This relation persisted after adjusting AGD for weight, height and age (ß = 0.016, 95% confidence interval: 0.10-0.21; P < 0.001). The Spearman test showed a significant negative correlation for the severity of hypospadias with all the three AGD measures. Analysis of variance between anterior, middle and posterior subgroups showed a significant reduction in mean AGD-AS (P = 0.003) and AGD-2 (P = 0.008). LIMITATIONS, REASONS FOR CAUTION: No data were collected pertaining to in utero exposure to endocrine disrupting chemicals (EDCs) or cigarette smoke, or current diet and environmental exposure to EDCs, which may have influenced the AGD. Family history of genital malformation and use of IVF were not known. There may have been a selection bias as only boys presenting to our clinic were included. WIDER IMPLICATIONS OF THE FINDINGS: The findings suggest that prenatal androgens during early gestation influence development of the male reproductive system and support the existence of a MPW in humans. Of the three AGDs, AGD-AS may be the most reliable biomarker of this in utero androgen action. However, no direct link to any specific exposure leading to shortened AGD in pre-pubertal boys with hypospadias could be determined. Further large scale multi-center studies are needed to understand this association better. STUDY FUNDING/COMPETING INTERESTS: Funding was from the Hypospadias Foundation. No conflicts of interest to disclose.

Transverse preputial onlay island flap urethroplasty for single-stage correction of proximal hypospadias.

AIMS AND OBJECTIVES: Transverse preputial onlay island flap urethroplasty (TPOIF) was described initially for distal hypospadias, but has seen extended application for proximal hypospadias. We describe a set of modifications in the technique and results in a large series of proximal hypospadias. MATERIALS AND METHODS: All children who underwent TPOIF repair for proximal hypospadias (proximal penile, penoscrotal and scrotal) from June 2006 to June 2013 by a single surgeon were prospectively followed till June, 2014. A standard technique and postoperative protocol were followed. Salient points to be emphasized in the technique: (1) dissection of the dartos pedicle till penopubic junction to prevent penile torsion, (2) incorporation of the spongiosum in the urethroplasty, (3) midline urethral plate incision in glans (hinging the plate), (4) Dartos blanket cover on whole urethroplasty. RESULTS: Out of 136 children with proximal hypospadias, 92 children who underwent TPOIF formed the study group. Out of 92 children, 48 (52 %) children required a tunica albuginea plication for chordee correction. In total, 16 (17 %) patients developed 24 complications and 11 children (12 %) required second surgeries: fistula closure in 7 (with meatoplasty in 5), glansplasty for glans dehiscence in 2 and excision of diverticulum in 2. Two children required a third surgery. Only 5 children had a noticeable penile torsion (less than 30 degree), and 7 had a patulous meatus. CONCLUSIONS: Transverse preputial onlay island flap urethroplasty can deliver reliable cosmetic and functional outcomes in proximal hypospadias.

Maternal and infant characteristics influencing the anogenital distance and penile length in newborns.

Recent studies have suggested that maternal characteristics can affect reproductive health of offspring, possibly through pre-natal hormonal influence. Anogenital distance (AGD) is an anthropometric measure which is a sensitive reproductive endpoint of masculinisation. It provides a read-out of pre-natal androgen exposure and has been associated with several reproductive health outcomes in humans. We studied AGD and stretched penile length (SPL) in a large, racially homogenous sample of consecutive newborns to understand their association with maternal and infant characteristics. A prospective cross-sectional study involving measurement of AGD and SPL at birth was performed by a single trained observer. A total of 1077 newborns (553 males and 524 females) were included in final anthropometric analysis. The mean AGD of males was 2.56 ± 0.31 cm, and the mean AGD of females was 1.54 ± 0.17 cm. The mean SPL of males was 3.31 ± 0.38 cm. On multiple regression analysis, for both males and females, birthweight (ß = 0.229, P < 0.001 and ß = 0.135, P < 0.001, respectively) was modest but significant predictor for AGD. For SPL, only gestational age (ß = 0.054, P < 0.001) was found to be statistically significant predictor. There was no significant association observed for gravidity, parity and maternal age with both AGD and SPL. Thus, no maternal characteristics (age, gravidity, parity) influence AGD or SPL in human infants.

Shorter anogenital distance correlates with undescended testis: a detailed genital anthropometric analysis in human newborns.

STUDY QUESTION: Are the anogenital distance (AGD) and stretched penile length (SPL) shorter in human newborn males with cryptorchidism? SUMMARY ANSWER: AGD is significantly shorter in boys with undescended testis (UDT) and this correlation may indicate that both have a common antecedent early in gestation. WHAT IS KNOWN ALREADY: Animal studies have reported a critical time period during early gestation termed the male programming window (MPW) where androgen deficiency results in reduced AGD and penile length, as well as cryptorchidism and hypospadias. Two pilot human studies have explored this association but these studies were small and heterogeneous with regard to age, race and had selection bias. STUDY DESIGN, SIZE, DURATION: A prospective descriptive study involving measurement of AGD and SPL at birth in a racially homogenous sample of 1154 consecutive newborns was performed over a period of 6 months. All measurements were taken by a single trained observer (V.J.). PARTICIPANTS/MATERIALS, SETTING, METHODS: All consecutively born male infants at a community hospital were classified as having descended and or UDT. Testicular position in the undescended group was graded as high scrotal, inguinal or non-palpable. AGD (from the centre of anus to the junction of the smooth and rugated skin of scrotum) and SPL were measured. The AGD index (AGDi) was calculated by dividing AGD by cube root of birthweight. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 1154 infants examined, 624 were males and 71 had UDT. AGD was significantly shorter in infants with UDT when compared with infants with descended testis (mean ± SD; 2.21 ± 0.36 versus 2.56 ± 0.31 cm; P < 0.001). AGDi was also significantly shorter in infants with UDT (mean ± SD; 1.68 ± 0.27 versus 1.81 ± 0.20 cm/kg⁻³; P < 0.001). Significance was maintained even when preterm (P < 0.001) and low birthweight boys (LBW) (P < 0.001) were excluded. SPL was also significantly shorter in infants with UDT (Mean ± SD; 3.08 ± 0.52 versus 3.31 ± 0.38 cm; P < 0.001) but the significance was not maintained when preterm (P = 0.119) and LBW boys (P = 0.666) were excluded. Birthweight, gestational age and length adjusted regression models showed significantly shorter AGD in infants with UDT, but SPL was not different. Infants with higher position of testis appeared to have a shorter AGD and SPL but the correlation did not reach statistical significance. No difference in AGD or SPL was noted between boys with unilateral and bilateral UDT. LIMITATIONS, REASONS FOR CAUTION: The present study did not include data pertaining to maternal or newborn health status. Also parental drug exposure or occupational exposures to endocrine-disrupting chemicals was not studied. These may possibly affect genital anthropometric measurements. WIDER IMPLICATIONS OF THE FINDINGS: The study strengthens the hypothesis of existence of MPW in humans. Shorter AGD in cryptorchid infants may reflect the effect of androgen disruption or deficiency during MPW. AGD may be a more reliable non-invasive marker of androgen action during MPW than SPL to predict reproductive outcomes in humans.

Undescended testis and torsion: is the risk understated?

Undescended testis (UDT) is seen in 3% to 5% of all newborn boys. Complications such as infertility and malignant transformation have been well documented in UDT. However, torsion of a UDT can also occur and the diagnosis is often missed or delayed, leading to loss of testis. This event may occur even before the currently recommended age for surgery, which is at 6-9 months. We present a case series of six children with torsion of undescended testes and their subsequent diagnosis and management. The risk of torsion of UDT is understated. Paediatricians should be educated about this complication and torsion should be included in the differential diagnosis when a boy with an empty scrotum presents with acute abdomen or red and tender swelling in the groin, as early detection and intervention can help salvage the testes.

Local steroid therapy as the first-line treatment for boys with symptomatic phimosis - a long-term prospective study.

AIM: Phimosis is a common paediatric urological disorder and often necessitates circumcision. We prospectively evaluated local steroid therapy (LST) as the first choice therapy for such children. METHODS: Two hundred and sixty symptomatic boys up to 15 years of age (mean 34 months) with phimosis were started on betamethasone dipropionate (0.05%) application on gently stretched prepuce twice a day. Follow-up visits were arranged at the end of weeks 1, 2 and 4 and 6 months. Grade of phimosis was objectively graded. RESULTS: Ninety one percent of the boys showed a successful outcome at the end of 4 weeks; 72% responded in first week, further 16% responded in week 2, and only 2.6% achieved alleviation of phimosis on further application of LST beyond 2 weeks. Fourty two (17.8%) boys had a recurrence of phimosis on a long-term follow-up (mean - 25.4 months, range 6-48 months); thus, the long-term success rate was 77%, while 60 (23%) boys underwent surgery. CONCLUSION: Local steroid therapy is safe and successful in alleviating symptomatic tight foreskin in a large majority of children. The response can be seen as early as 1 week; most of the children respond by week 2 and continuing therapy further may not be very effective.

3D multidetector CT angiographic evaluation of intralobular bronchopulmonary sequestration.

We report a case of intralobar pulmonary sequestration with special emphasis on computed tomography (CT) angiography in determining the arterial supply and venous drainage, thus providing a detailed knowledge of the vasculature, which is of vital importance in surgery. The 3D volume rendering technique and maximum intensity projection images provide the vascular road map for the surgeon.