Factors Associated With Additional Axillary Disease in Patients With Positive Sentinel Lymph Nodes After Neoadjuvant Chemotherapy for Breast Cancer.

Background: In previous studies, breast cancer patients with positive sentinel lymph node(s) (SLN) after neoadjuvant chemotherapy (NAC) frequently had additional nonSLN involvement. Per guidelines, residual SLN disease warrants completion axillary lymph node dissection (cALND), which has increased morbidity. Given recent improvements in NAC, we hypothesized that nonSLN positivity may be lower than previously reported for certain subgroups.Methods: We retrospectively reviewed breast cancer patients who received NAC and had positive lymph nodes on SLN biopsy or targeted axillary dissection and underwent cALND at one institution in 1/2018-8/2023. Associations between nonSLN positivity and clinicopathologic factors were assessed with Fisher's exact test and multivariable logistic regression.Results: There were 122 female patients. Median age was 48 years. Initially, 15 patients (12.3%) were cN0 and 107 patients (87.7%) were cN1. Largest SLN deposit was macrometastasis in 96 patients (78.7%), micrometastasis in 23 patients (18.9%), and isolated tumor cells in 3 patients (2.5%). Overall, 53 patients (43.4%) had nonSLN involvement. NonSLN positivity was higher in patients with cN1, ER+ HER2-, ypT2-3, SLN macrometastasis, and multiple positive SLN. On multivariable analysis, cN1 and ER+ HER2- remained associated with nonSLN positivity.Discussion: Among patients with positive SLN after NAC, clinically node positive and ER+ HER2- patients were more likely to have nonSLN involvement. Our findings support guidelines to consider omitting cALND in clinically node negative patients. With improving NAC, optimal axillary sampling, and radiation, omitting cALND may be safe in some clinically node positive triple negative or HER2+ patients with low volume residual disease, but further research is needed.

Strategic social decision making undergoes significant changes in typically developing and autistic early adolescents.

Information sampling about others' trustworthiness prior to cooperation allows humans to minimize the risk of exploitation. Here, we examined whether early adolescence or preadolescence, a stage defined as in between childhood and adolescence, is a significant developmental period for strategic social decisions. We also sought to characterize differences between autistic children and their typically developing (TD) peers. TD (N = 48) and autistic (N = 56) 8- to 12-year-olds played an online information sampling trust game. While both groups adapted their information sampling and cooperation to the various trustworthiness levels of the trustees, groups differed in how age and social skills modulated task behavior. In the TD group social skills were a stronger overall predictor of task behavior. In the autistic group, age was a stronger predictor and interacted with social skills. Computational modeling revealed that both groups used the same heuristic information sampling strategy-albeit older TD children were more efficient as reflected by decreasing decision noise with age. Autistic children had lower prior beliefs about the trustee's trustworthiness compared to TD children. These lower priors indicate that children believed the trustees to be less trustworthy. Lower priors scaled with lower social skills across groups. Notably, groups did not differ in prior uncertainty, meaning that the priors of TD and autistic children were equally strong. Taken together, we found significant development in information sampling and cooperation in early adolescence and nuanced differences between TD and autistic children. Our study highlights the importance of deep phenotyping of children including clinical measures, behavioral experiments and computational modeling. RESEARCH HIGHLIGHTS: We specified how early adolescents with and without an autism diagnosis sampled information about their interaction partners and made cooperation decisions in a strategic game. Early adolescence is a significant developmental period for strategic decision making, marked by significant changes in information sampling efficiency and adaptivity to the partner's behavior. Autistic and non-autistic groups differed in how age and social skills modulated task behavior; in non-autistic children behavior was more indicative of overall social skills. Computational modeling revealed differences between autistic and non-autistic groups in their initial beliefs about cooperation partners; autistic children expected their partners to be less trustworthy.

A tale of two waves: Delineating diverse genomic and transmission landscapes driving the COVID-19 pandemic in Pune, India.

BACKGROUND: Modern response to pandemics, critical for effective public health measures, is shaped by the availability and integration of diverse epidemiological outbreak data. Tracking variants of concern (VOC) is integral to understanding the evolution of SARS-CoV-2 in space and time, both at the local level and global context. This potentially generates actionable information when integrated with epidemiological outbreak data. METHODS: A city-wide network of researchers, clinicians, and pathology diagnostic laboratories was formed for genome surveillance of COVID-19 in Pune, India. The genomic landscapes of 10,496 sequenced samples of SARS-CoV-2 driving peaks of infection in Pune between December-2020 to March-2022, were determined. As a modern response to the pandemic, a "band of five" outbreak data analytics approach was used. This integrated the genomic data (Band 1) of the virus through molecular phylogenetics with key outbreak data including sample collection dates and case numbers (Band 2), demographics like age and gender (Band 3-4), and geospatial mapping (Band 5). RESULTS: The transmission dynamics of VOCs in 10,496 sequenced samples identified B.1.617.2 (Delta) and BA(x) (Omicron formerly known as B.1.1.529) variants as drivers of the second and third peaks of infection in Pune. Spike Protein mutational profiling during pre and post-Omicron VOCs indicated differential rank ordering of high-frequency mutations in specific domains that increased the charge and binding properties of the protein. Time-resolved phylogenetic analysis of Omicron sub-lineages identified a highly divergent BA.1 from Pune in addition to recombinant X lineages, XZ, XQ, and XM. CONCLUSIONS: The band of five outbreak data analytics approach, which integrates five different types of data, highlights the importance of a strong surveillance system with high-quality meta-data for understanding the spatiotemporal evolution of the SARS-CoV-2 genome in Pune. These findings have important implications for pandemic preparedness and could be critical tools for understanding and responding to future outbreaks.

Kidney and urinary tract involvement in systemic mastocytosis.

Systemic mastocytosis (SM) is a disorder of excessive mast cell accumulation in tissues due to a somatic gain-of-function mutation, commonly in the KIT gene, which prevents apoptosis of mast cells. Whereas bone marrow, skin, lymph nodes, spleen and gastrointestinal tract are commonly involved, kidneys are rarely involved directly by SM. However, there are increasing reports of indirect kidney involvement in patients with SM. Novel anti-neoplastic agents to treat advanced forms of SM include non-specific tyrosine kinase inhibitors, which are reported to be associated with kidney dysfunction in some patients. SM is also associated with immune-mediated glomerulonephritis (GN) such as mesangioproliferative GN, membranous nephropathy and diffuse proliferative GN. Kidney injury, in the form of monoclonal deposition disease and primary light chain amyloidosis, is reported in SM associated with plasma cell dyscrasia. In this narrative review we discuss the various ways kidneys (and the urinary tract) are involved in patients with SM.

Mixed Neuroendocrine and Non-Neuroendocrine Neoplasm of Pancreas: What Do We Know, What Have We Learnt?

Pancreatic adeno-mixed neuroendocrine non-endocrine (pMINEN) tumors are extremely rare [Pancreatology. 2021;21(1):224-235]. They are known to have distal metastasis at presentation and have a comparatively lower survival rate than similar staged neuroendocrine (NEN) carcinoma, adenocarcinoma, and small-cell lung tumor from which its treatment patterns are extrapolated. Also, very less is known about its molecular structure and natural courses. There is a dearth of data about pMINEN in the literature, and also there is a lack of large multicentral trials due to which the MINEN tumors do not have a standard universal management protocol. We discuss here the clinical dilemmas that arise during diagnosis and reporting and urge to form a multicentric trial to formulate a focused protocolized approach. We describe here our encounter with a pancreatic head lesion which on immunohistochemical analysis turned out to be a pMINEN with moderately differentiating ductal adenocarcinoma and low-grade NEN tumor. Radical R0 surgery with multimodal treatment (chemotherapy + radiotherapy) gains improved survival in long term.

Early detection of glomerular dysfunction and renal tubulopathy in children with sickle cell disease in India.

BACKGROUND: Sickle cell disease causes microvascular occlusion in different vascular beds. In kidneys, it leads to occult glomerular dysfunction causing asymptomatic microalbuminuria, proximal tubulopathy causing hyposthenuria and increased free water loss and distal tubulopathy causing poor urine acidification. We studied the prevalence of various types of renal dysfunction, the ability of different tests to detect it at an early stage and the correlation of these parameters in children receiving hydroxyurea (HU). PROCEDURE: Fifty-six children (sample size calculated using SAS9.2 package) attending paediatric clinical services in a tertiary care hospital between 2 and 12 years of age diagnosed by high-performance liquid chromatography (HPLC) were enrolled. Their demographic and laboratory data including renal and urine parameters were collected. Parameters like fractional excretion of sodium (FeNa), trans tubular potassium gradient (TtKg) and free water clearance (TcH2O) were derived by calculations. Data were analysed using IBM SPSS Version 21.0 and Microsoft Office Excel 2007. RESULTS: We found a significant number of children to have microalbuminuria (17.8%), hyposthenuria (30.4%) and impaired renal tubular potassium excretion (TtKg) (81.3%). A significant correlation was found between the dose of HU with urine osmolality (p < 0.0005) and free water clearance (p = 0.002), while all parameters showed a significant correlation with compliance with HU. Derangement in urine microalbumin and TcH2O correlated significantly with low mean haemoglobin levels (<9 g/dl). CONCLUSION: Renal dysfunction is common in children with SCD and can be detected early using simple urine parameters and can be prevented with an early and appropriate dosage of HU with good compliance.

Kinetics of Arf1 inactivation regulates Golgi organisation and function in non-adherent fibroblasts.

Arf1 belongs to the Arf family of small GTPases that localise at the Golgi and plasma membrane. Active Arf1 plays a crucial role in regulating Golgi organisation and function. In mouse fibroblasts, loss of adhesion triggers a consistent drop (∼50%) in Arf1 activation that causes the Golgi to disorganise but not fragment. In suspended cells, the trans-Golgi (GalTase) disperses more prominently than cis-Golgi (Man II), accompanied by increased active Arf1 (detected using GFP-ABD: ARHGAP10 Arf1 binding domain) associated with the cis-Golgi compartment. Re-adhesion restores Arf1 activation at the trans-Golgi as it reorganises. Arf1 activation at the Golgi is regulated by Arf1 Guanine nucleotide exchange factors (GEFs), GBF1, and BIG1/2. In non-adherent fibroblasts, the cis-medial Golgi provides a unique setting to test and understand the role GEF-mediated Arf1 activation has in regulating Golgi organisation. Labelled with Man II-GFP, non-adherent fibroblasts treated with increasing concentrations of Brefeldin-A (BFA) (which inhibits BIG1/2 and GBF1) or Golgicide A (GCA) (which inhibits GBF1 only) comparably decrease active Arf1 levels. They, however, cause a concentration-dependent increase in cis-medial Golgi fragmentation and fusion with the endoplasmic reticulum (ER). Using selected BFA and GCA concentrations, we find a change in the kinetics of Arf1 inactivation could mediate this by regulating cis-medial Golgi localisation of GBF1. On loss of adhesion, a ∼50% drop in Arf1 activation over 120 min causes the Golgi to disorganise. The kinetics of this drop, when altered by BFA or GCA treatment causes a similar decline in Arf1 activation but over 10 min. This causes the Golgi to now fragment which affects cell surface glycosylation and re-adherent cell spreading. Using non-adherent fibroblasts this study reveals the kinetics of Arf1 inactivation, with active Arf1 levels, to be vital for Golgi organisation and function.

A Phase II Single-arm Study of Palbociclib in Patients With HER2-positive Breast Cancer With Brain Metastases and Analysis of ctDNA in Patients With Active Brain Metastases.

INTRODUCTION: Palbociclib is highly efficacious and well tolerated in hormone-receptor positive (HR+) metastatic breast cancer (BC) but its activity for HER2+ BC with brain metastases (BM) is unknown. METHODS: In a single-arm phase II study we evaluated palbociclib with trastuzumab for patients with HER2+ MBC and BM. The primary endpoint was BM response rate. Circulating tumor DNA (ctDNA) was evaluated at baseline, and in a subset of patients at cycle 3 and progression. We also retrospectively identified additional patients with metastatic BC, active BM, and a ctDNA assessment prior to therapy for BM. RESULTS: Twelve patients with HER2+ MBC were enrolled, 4 with HR+ and 8 with HR- disease. No responses were seen. Best response was stable disease for 6 patients and progressive disease for 6 patients. The median PFS was 2.2 months, interquartile range (IQR) was 1.56 to 3.63 months. The median OS was 13.1 months and IQR was 9.4 to 23.8 months The CNS was the primary site of progression for all patients. The median variant allele fraction (VAF) of the dominant variant in each patient was 0.18% (interquartile range [IQR] 0.12%-0.47%) with a median number of somatic alterations of 1. We additionally evaluated ctDNA results from 26 patients with BC and active BM, among whom the median VAF was 11.8% (IQR 3.9%-27.3%) with a median number of alterations was 6 (IQR 4-9). Notably, progressive systemic disease was significantly less frequent in the trial cohort compared with additional retrospectively identified patients (8% vs. 81%). CONCLUSION: Palbociclib did not demonstrate activity in HER2+ MBC with BM. Patients with progressive BM but stable, responding, or absent systemic disease have low VAF and number of alterations detected by ctDNA analysis from blood.

Ganglioneuroblastoma arising in a Mature Cystic Teratoma of Ovary: Report and Literature review of an uncommon neoplasm.

•Somatic neoplasms in Mature Cystic Teratoma are uncommon; Ganglioneuroblastoma is rare, this is 2nd reported case.•Due to rarity, it can pose a diagnostic challenge for Pathologists, and management and staging conundrum for Gynecologists.•Morphological differentials include immature teratoma, glial neoplasms arising in teratoma, and carcinoid.

Development and Initial Validation of a Novel Professional Aesthetic Scale for the Female Abdomen.

BACKGROUND: A growing body of literature describes abdominal aesthetic goals to tailor surgical and nonsurgical treatment options to meet patient goals. The authors aimed to integrate layperson perceptions into the design of a novel professional aesthetic scale for the abdomen. METHODS: An iterative process of expert consensus was used to choose five domains: abdominal muscle lines, abdominal shape, scar, skin, and umbilicus. A survey was developed to measure global and domain-specific aesthetic preferences on five abdomens. This was distributed through Amazon Mechanical Turk to 340 respondents. Principal component analysis was used to integrate survey data into weights for each of the scale's subquestions. Attending plastic surgeons then rated abdomens using the final scale, and reliability and validity were calculated. RESULTS: The final scale included 11 subquestions-hourglass shape, bulges, hernia, infraumbilical skin, supraumbilical skin, umbilicus shape, umbilicus medialization position, umbilicus height position, semilunar lines, central midline depression, and scar-within the five domains. Central midline depression held the highest weight (16.1 percent) when correlated with global aesthetic rating, followed by semilunar lines (15.8 percent) and infraumbilical skin (11.8 percent). The final scale demonstrated strong validity (Pearson r = 0.99) and was rated as easy to use by seven attending plastic surgeons. CONCLUSIONS: The final scale is the first published professional aesthetic scale for the abdomen that aims to integrate layperson opinion. This analysis and survey data provide insights into the importance of 11 components in overall aesthetic appeal of the abdomen.

Presentation and surgical management of a patient with a true cleft mandible.

Clefts involving the mandible and lower lip are very rare, with less than 80 cases having been reported worldwide. The objective of this case report is to highlight this unusual type of facial cleft, and to present the principle features and management typically associated with it. We carefully describe our surgical planning and management of the patient alongside a compilation and comparison of different surgical techniques described in the literature thus far. In this report, we discuss a patient with a cleft of the lower lip, true cleft mandible with independent movements of his mandibular segments, ankyloglossia, and a fistula extending from the mandible to the suprasternal notch complicated with congenital heart abnormalities. We explore the different approaches of when to close the hard and soft tissues, however, there is still no clear surgical protocol for treating cleft mandibles but with more cases and their management and outcomes being reported, this is something which will be useful to develop.

Targeting Predialysis Glucose up to 180 mg/dl Reduces Glycemic Variability in End Stage Diabetic Nephropathy.

Context: Glycemic variability plays a major role in the development as well as the progression of cardiovascular disease in diabetes. Aims: We compared the mean plasma glucose and glycemic variability (GV) parameters on and off hemodialysis (HD) in patients with End-Stage Diabetic Nephropathy (ESDN) and End-Stage Renal Disease (ESRD). Settings and Design: Cross-sectional study. Methods and Material: We included 23 ESDN and 6 ESRD patients who underwent continuous glucose monitoring (CGM) (iPro2) for 6 days and a glucose-free dialysate for 4 hours thrice weekly. EasyGV software was used to calculate the variability parameters {mean glucose, Time in range (TIR), Time above and below range (TAR/TBR), CV (Coefficient of Variation) and MAGE}. Statistical Analysis Used: The quantitative data variables were expressed by using mean and SD. Unpaired t-test was used to compare the two groups. P value <0.05 was considered significant. Results: In the ESDN group, TIR was significantly lower whereas TAR and TBR were significantly higher on HD day. MAGE (101.88 ± 40.5 v/s 89.46 ± 30.0, P < 0.007) and CV (29.41% v/s 21.67%) were higher on HD day. Subjects with pre-HD glucose values ≥180 mg/dl (Group B, n = 24) had a rapid drop with a delayed higher rise in glucose values than those with pre-HD glucose values <180 mg/dl (Group A, n = 27). Ten patients had 13 episodes of hypoglycemia. The CGM parameters were not different in the ESRD group. Conclusions: Targeting a pre- HD glucose value <180 mg/dl could be a good strategy to prevent larger fluctuation during and post HD.

Mesh Repair of Rectus Diastasis for Abdominoplasty is Safer than Suture Plication.

Concerns regarding infection, extrusion, and pain have traditionally precluded the use of mesh to treat severe rectus diastasis during abdominoplasty in the United States. We describe a mesh abdominoplasty technique, and we hypothesize that the complication rate using mesh is greater than the complication rate of suture plication. METHODS: Inclusion criteria for mesh abdominoplasty were patients who (1) had retrorectus planar mesh for repair of rectus diastasis, (2) did not have concurrent ventral hernia, and (3) underwent skin tailoring. Patients who underwent rectus plication with suture, and met criteria 2 and 3 above were included in a sample of consecutive standard abdominoplasty patients. The primary endpoint was surgical site occurrence at any time after surgery, as determined with review of their office and hospital medical records. Secondary endpoints included surgical site infection, revision rates, postoperative course, and aesthetics assessed with their last set of office photographs. RESULTS: Surgical site occurrence rate was 0% of the 40 patients in the mesh group and 19% of the 37 patients in the standard group (P = 0.005); rates of soft-tissue revision were 23% in the mesh group and 27% in the standard group (P = 0.84). As to aesthetics, the mesh abdominoplasty patients had mean statistically lower preoperative scores in comparison with the standard plication group (65.8 ± 11.6 versus 70.3 ± 11.4, P = 0.0013). The mesh group had a statistical improvement to 75.9 ± 12.6 (P < 0.0001), whereas the standard plication group improved to 82.5 ± 11.4 (P < 0.0001). CONCLUSIONS: Retrorectus mesh placement in a cohort of patients with severe rectus diastasis had a complication rate lower than that seen in a cohort of patients with less severe rectus diastasis, therefore negating our original hypothesis. This was done without compromising aesthetic improvement.

Can Breast Implants Induce Breast Cancer Immunosurveillance? An Analysis of Antibody Response to Breast Cancer Antigen following Implant Placement.

BACKGROUND: Women with cosmetic breast implants have significantly lower rates of subsequent breast cancer than the general population (relative risk, 0.63; 95 percent CI, 0.56 to 0.71). The authors hypothesize that breast implant-induced local inflammation stimulates immunosurveillance recognition of breast tumor antigen. METHODS: Sera were collected from two cohorts of healthy women: women with long-term breast implants (i.e., breast implants for >6 months) and breast implant-naive women. Antibody responses to breast tumor antigens were tested by enzyme-linked immunosorbent assay and compared between cohorts by unpaired t test. Of the implant-naive cohort, nine women underwent breast augmentation, and antibody responses before and after implant placement were compared by paired t test. RESULTS: Sera were collected from 104 women: 36 (34.6 percent) long-term breast implants and 68 (65.4 percent) implant-naive women. Women with long-term breast implants had higher antibody responses than implant-naive women to mammaglobin-A (optical density at 450 nm, 0.33 versus 0.22; p = 0.003) and mucin-1 (optical density at 450 nm, 0.42 versus 0.34; p = 0.02). There was no difference in antibody responses to breast cancer susceptibility gene 2, carcinoembryonic antigen, human epidermal growth factor receptor-2, or tetanus. Nine women with longitudinal samples preoperatively and 1 month postoperatively demonstrated significantly elevated antibody responses following implant placement to mammaglobin-A (mean difference, 0.13; p = 0.0002) and mucin-1 (mean difference 0.08; p = 0.02). There was no difference in postimplant responses to other breast tumor antigens, or tetanus. CONCLUSIONS: Women with long-term breast implants have higher antibody recognition of mammaglobin-A and mucin-1. This study provides the first evidence of implant-related immune responses to breast cancer antigens. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Vitamin C Deficiency and Oxidant Levels in Children With Transfusion-Dependent b-Thalassemia.

OBJECTIVES: To study vitamin C levels in children with transfusion-dependent b-thalassemia and correlate with age, transfusions received and iron overload; and to study the effect of administering vitamin C on its levels and Malondialdehyde (MDA) in deficient patients. METHODS: This case-control study enrolled 100 children with transfusion-dependent b-thalassemia and 30 healthy controls. MDA levels before and after administration of vitamin C were performed randomly in 36 children with low vitamin C levels. RESULTS: 81/95 (85.3%) study subjects vs none in control group, had low plasma vitamin C levels (P<0.001). Vitamin C levels were low in 64 of 71 (74.7%) subjects with dietary deficiency, while none of the 19 (63.3%) controls with dietary deficiency had low levels (P=0.04). Increasing serum ferritin values correlated with vitamin C deficiency (P=0.02). The mean level of MDA reduced (P<0.001) with vitamin C supplementation. CONCLUSIONS: Low levels of vitamin C are common in children with thalassemia. Dietary counseling along with supplementation with vitamin C, in those with low levels may prevent oxidative stress.

A Survey of Primary Care Practices on Their Use of the Intensive Behavioral Therapy for Obese Medicare Patients.

OBJECTIVE: To fill the gap in knowledge on systematic differences between primary care practices (PCP) that do or do not provide intensive behavioral therapy (IBT) for obese Medicare patients. METHODS: A mixed modality survey (paper and online) of primary care practices obtained from a random sample of Medicare databases and a convenience sample of practice-based research network practices. KEY RESULTS: A total of 287 practices responded to the survey, including 140 (7.4% response rate) from the random sample and 147 (response rate not estimable) from the convenience sample. We found differences between the IBT-using and non-using practices in practice ownership, patient populations, and participation in Accountable Care Organizations. The non-IBT-using practices, though not billing for IBT, did offer some other assistance with obesity for their patients. Among those who had billed for IBT, but stopped billing, the most commonly cited reason was billing difficulties. Many providers experienced denied claims due to billing complexities. CONCLUSIONS: Although the Centers for Medicare and Medicaid Services established payment codes for PCPs to deliver IBT for obesity in 2011, very few providers submitted fee-for-service claims for these services after almost 10 years. A survey completed by both a random and convenience sample of practices using and not using IBT for obesity payment codes revealed that billing for these services was problematic, and many providers that began using the codes discontinued using them over the past 7 years.

Lateral and Inferior Implant Malposition in Prosthetic Breast Reconstruction: Incidence and Risk Factors.

Implant malposition is one of the most common causes for revision after prosthetic breast reconstruction. There is a paucity of research on the incidence, etiology and risk factors for implant malposition in this setting. METHODS: Retrospective review of a single surgeon's prosthetic breast reconstructions was performed. Variables collected included age, BMI, radiation, chemotherapy, implant characteristics and malposition location (inferior or lateral). Binary logistic regression identified risk factors for malposition. Chi-square test assessed malposition rate as a function of implant volume to BMI subgroups. RESULTS: Of 836 breasts, 82 (9.8%) exhibited implant malposition. Risk factors for any malposition were older age (OR 1.05, 95% CI 1.02-1.07), BMI<25 (OR 1.64, 95% CI 1.00-2.70) and bilateral reconstruction (OR 13.41, 95% CI 8.50-21.16). Risk factors for inferior malposition were older age (OR 1.04, 95% CI 1.01-1.06), BMI<25 (OR 3.43, 95% CI 1.88-6.26) and bilateral reconstructions (OR 11.50, 95% CI 6.79-19.49), while risk factors for lateral malposition were only older age (OR 1.05, 95% CI 1.02-1.08) and bilateral reconstructions (OR 7.08, 95% CI 4.09-12.26). Post-mastectomy radiation was protective against lateral malposition (OR 0.30, 95% CI 0.10-0.88). Stratification by implant volume and BMI demonstrated patient subgroups with distinct patterns of malposition (incidence 0.0% versus 10.9%, P = 0.001). CONCLUSIONS: This is the first study to identify risk factors for implant malposition after prosthetic breast reconstruction. Different risk factors contributed to malposition in different directions. The effect of implant size on malposition was mediated through BMI, highlighting the interplay of implant and patient characteristics with respect to malposition.

A study of glycemic variability in patients with type 2 diabetes mellitus with obstructive sleep apnea syndrome using a continuous glucose monitoring system.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) in association with Type 2 Diabetes Mellitus (DM) may result in increased glycemic variability affecting the glycemic control and hence increasing the risk of complications associated with diabetes. We decided to assess the Glycemic Variability (GV) in patients with type 2 diabetes with OSAS and in controls. We also correlated the respiratory disturbance indices with glycemic variability indices. METHODS: After fulfilling the inclusion and exclusion criteria patients from the Endocrinology and Pulmonology clinics underwent modified Sleep Apnea Clinical Score (SACS) followed by polysomnography (PSG). Patients were then divided into 4 groups: Group A (DM with OSAS, n = 20), Group B (DM without OSAS, n = 20), Group C (Non DM with OSAS, n = 10) and Group D (Non DM without OSAS, n = 10). Patients in these groups were subjected to continuous glucose monitoring using the Medtronic iPro2 and repeat PSG. Parameters of GV: i.e. mean glucose, SD (standard Deviation), CV (Coefficient of Variation), Night SD, Night CV, MAGE and NMAGE were calculated using the Easy GV software. GV parameters and the respiratory indices were correlated statistically. Quantitative data was expressed as mean, standard deviation and median. The comparison of GV indices between different groups was performed by one-way analysis of variance (ANOVA) or Kruskal Wallis (for data that failed normality). Correlation analysis of AHI with GV parameters was done by Pearson correlation. RESULTS: All the four groups were adequately matched for age, sex, Body Mass Index (BMI), waist circumference (WC) and blood pressure (BP). We found that the GV parameters Night CV, MAGE and NMAGE were significantly higher in Group A as compared to Group B (p values < 0.05). Similarly Night CV, MAGE and NMAGE were also significantly higher in Group C as compared to Group D (p value < 0.05). Apnea-hypopnea index (AHI) correlated positively with Glucose SD, MAGE and NMAGE in both diabetes (Group A plus Group B) and non- diabetes groups (Group C plus Group D). CONCLUSIONS: OSAS has a significant impact on the glycemic variability irrespective of glycemic status. AHI has moderate positive correlation with the glycemic variability.

Targeted Muscle Reinnervation Improves Residual Limb Pain, Phantom Limb Pain, and Limb Function: A Prospective Study of 33 Major Limb Amputees.

BACKGROUND: Targeted muscle reinnervation is an emerging surgical technique to treat neuroma pain whereby sensory and mixed motor nerves are transferred to nearby redundant motor nerve branches. In a recent randomized controlled trial, targeted muscle reinnervation was recently shown to reduce postamputation pain relative to conventional neuroma excision and muscle burying. QUESTIONS/PURPOSES: (1) Does targeted muscle reinnervation improve residual limb pain and phantom limb pain in the period before surgery to 1 year after surgery? (2) Does targeted muscle reinnervation improve Patient-reported Outcome Measurement System (PROMIS) pain intensity and pain interference scores at 1 year after surgery? (3) After 1 year, does targeted muscle reinnervation improve functional outcome scores (Orthotics Prosthetics User Survey [OPUS] with Rasch conversion and Neuro-Quality of Life [Neuro-QOL])? METHODS: Data on patients who were ineligible for randomization or declined to be randomized and underwent targeted muscle reinnervation for pain were gathered for the present analysis. Data were collected prospectively from 2013 to 2017. Forty-three patients were enrolled in the study, 10 of whom lacked 1-year follow-up, leaving 33 patients for analysis. The primary outcomes measured were the difference in residual limb and phantom limb pain before and 1 year after surgery, assessed by an 11-point numerical rating scale (NRS). Secondary outcomes were change in PROMIS pain measures and change in limb function, assessed by the OPUS Rasch for upper limbs and Neuro-QOL for lower limbs before and 1 year after surgery. RESULTS: By 1 year after targeted muscle reinnervation, NRS scores for residual limb pain from 6.4 ± 2.6 to 3.6 ± 2.2 (mean difference -2.7 [95% CI -4.2 to -1.3]; p < 0.001) and phantom limb pain decreased from 6.0 ± 3.1 to 3.6 ± 2.9 (mean difference -2.4 [95% CI -3.8 to -0.9]; p < 0.001). PROMIS pain intensity and pain interference scores improved with respect to residual limb and phantom limb pain (residual limb pain intensity: 53.4 ± 9.7 to 44.4 ± 7.9, mean difference -9.0 [95% CI -14.0 to -4.0]; residual limb pain interference: 60.4 ± 9.3 to 51.7 ± 8.2, mean difference -8.7 [95% CI -13.1 to -4.4]; phantom limb pain intensity: 49.3 ± 10.4 to 43.2 ± 9.3, mean difference -6.1 [95% CI -11.3 to -0.9]; phantom limb pain interference: 57.7 ± 10.4 to 50.8 ± 9.8, mean difference -6.9 [95% CI -12.1 to -1.7]; p ≤ 0.012 for all comparisons). On functional assessment, OPUS Rasch scores improved from 53.7 ± 3.4 to 56.4 ± 3.7 (mean difference +2.7 [95% CI 2.3 to 3.2]; p < 0.001) and Neuro-QOL scores improved from 32.9 ± 1.5 to 35.2 ± 1.6 (mean difference +2.3 [95% CI 1.8 to 2.9]; p < 0.001). CONCLUSIONS: Targeted muscle reinnervation demonstrates improvement in residual limb and phantom limb pain parameters in major limb amputees. It should be considered as a first-line surgical treatment option for chronic amputation-related pain in patients with major limb amputations. Additional investigation into the effect on function and quality of life should be performed. LEVEL OF EVIDENCE: Level IV, therapeutic study.