Implementation of a Multidimensional Strategy to Reduce Post-PCI Bleeding Risk.

BACKGROUND: The American College of Cardiology Reduce the Risk: PCI Bleed Campaign was a hospital-based quality improvement campaign designed to reduce post-percutaneous coronary intervention (PCI) bleeding events. The aim of the campaign was to provide actionable evidence-based tools for participants to review, adapt, and adopt, depending upon hospital resources and engagement. METHODS: We used data from 8 757 737 procedures in the National Cardiovascular Data Registry between 2015 and 2021 to compare patient and hospital characteristics and bleeding outcomes among campaign participants (n=195 hospitals) and noncampaign participants (n=1384). Post-PCI bleeding risk was compared before and after campaign participation. Multivariable hierarchical logistic regression was used to determine the adjusted association between campaign participation and post-PCI bleeding events. Prespecified subgroups were examined. RESULTS: Campaign hospitals were more often higher volume teaching facilities located in urban or suburban locations. After adjustment, campaign participation was associated with a significant reduction in the rate of bleeding (bleeding: adjusted odds ratio, 0.61 [95% CI, 0.53-0.71]). Campaign hospitals had a greater decrease in bleeding events than noncampaign hospitals. In a subgroup analysis, the reduction in bleeding was noted in non-ST-segment-elevation acute coronary syndrome and ST-segment-elevation myocardial infarction patients, but no significant reduction was seen in patients without acute coronary syndrome. CONCLUSIONS: Participation in the American College of Cardiology Reduce the Risk: PCI Bleed Campaign was associated with a significant reduction in post-PCI bleeding. Our results underscore that national quality improvement efforts can be associated with a significant impact on PCI outcomes.

Interventions to Reduce Risk for Pathogen Spillover and Early Disease Spread to Prevent Outbreaks, Epidemics, and Pandemics.

The pathogens that cause most emerging infectious diseases in humans originate in animals, particularly wildlife, and then spill over into humans. The accelerating frequency with which humans and domestic animals encounter wildlife because of activities such as land-use change, animal husbandry, and markets and trade in live wildlife has created growing opportunities for pathogen spillover. The risk of pathogen spillover and early disease spread among domestic animals and humans, however, can be reduced by stopping the clearing and degradation of tropical and subtropical forests, improving health and economic security of communities living in emerging infectious disease hotspots, enhancing biosecurity in animal husbandry, shutting down or strictly regulating wildlife markets and trade, and expanding pathogen surveillance. We summarize expert opinions on how to implement these goals to prevent outbreaks, epidemics, and pandemics.

The Role of 3D Tractography in Skull Base Surgery: Technological Advances, Feasibility, and Early Clinical Assessment with Anterior Skull Base Meningiomas.

Objective The aim of this study is to determine feasibility of incorporating three-dimensional (3D) tractography into routine skull base surgery planning and analyze our early clinical experience in a subset of anterior cranial base meningiomas (ACM). Methods Ninety-nine skull base endonasal and transcranial procedures were planned in 94 patients and retrospectively reviewed with a further analysis of the ACM subset. Main Outcome Measures (1) Automated generation of 3D tractography; (2) co-registration 3D tractography with computed tomography (CT), CT angiography (CTA), and magnetic resonance imaging (MRI); and (3) demonstration of real-time manipulation of 3D tractography intraoperatively. ACM subset: (1) pre- and postoperative cranial nerve function, (2) qualitative assessment of white matter tract preservation, and (3) frontal lobe fluid-attenuated inversion recovery (FLAIR) signal abnormality. Results Automated 3D tractography, with MRI, CT, and CTA overlay, was produced in all cases and was available intraoperatively. ACM subset : 8 (44%) procedures were performed via a ventral endoscopic endonasal approach (EEA) corridor and 12 (56%) via a dorsal anteromedial (DAM) transcranial corridor. Four cases (olfactory groove meningiomas) were managed with a combined, staged approach using ventral EEA and dorsal transcranial corridors. Average tumor volume reduction was 90.3 ± 15.0. Average FLAIR signal change was -30.9% ± 58.6. 11/12 (92%) patients (DAM subgroup) demonstrated preservation of, or improvement in, inferior fronto-occipital fasciculus volume. Functional cranial nerve recovery was 89% (all cases). Conclusion It is feasible to incorporate 3D tractography into the skull base surgical armamentarium. The utility of this tool in improving outcomes will require further study.

Improving rural health care reduces illegal logging and conserves carbon in a tropical forest.

Tropical forest loss currently exceeds forest gain, leading to a net greenhouse gas emission that exacerbates global climate change. This has sparked scientific debate on how to achieve natural climate solutions. Central to this debate is whether sustainably managing forests and protected areas will deliver global climate mitigation benefits, while ensuring local peoples' health and well-being. Here, we evaluate the 10-y impact of a human-centered solution to achieve natural climate mitigation through reductions in illegal logging in rural Borneo: an intervention aimed at expanding health care access and use for communities living near a national park, with clinic discounts offsetting costs historically met through illegal logging. Conservation, education, and alternative livelihood programs were also offered. We hypothesized that this would lead to improved health and well-being, while also alleviating illegal logging activity within the protected forest. We estimated that 27.4 km2 of deforestation was averted in the national park over a decade (∼70% reduction in deforestation compared to a synthetic control, permuted P = 0.038). Concurrently, the intervention provided health care access to more than 28,400 unique patients, with clinic usage and patient visitation frequency highest in communities participating in the intervention. Finally, we observed a dose-response in forest change rate to intervention engagement (person-contacts with intervention activities) across communities bordering the park: The greatest logging reductions were adjacent to the most highly engaged villages. Results suggest that this community-derived solution simultaneously improved health care access for local and indigenous communities and sustainably conserved carbon stocks in a protected tropical forest.

White Matter Governed Superior Frontal Sulcus Surgical Paradigm: A Radioanatomic Microsurgical Study-Part II.

BACKGROUND: Kocher's point (KP) and its variations have provided standard access to the frontal horn (FH) for over a century. Anatomic understanding of white matter tracts (WMTs) has evolved, now positioning us to better inform the optimal FH trajectory. OBJECTIVE: To (1) undertake a literature review analyzing entry points (EPs) to the FH; (2) introduce a purpose-built WMT-founded superior frontal sulcus parafascicular (SFSP)-EP also referred to as the Kassam-Monroy entry point (KM-EP); and (3) compare KM-EP with KP and variants with respect to WMTs. METHODS: (1) Literature review (PubMed database, 1892-2018): (a) stratification based on the corridor: i. ventricular catheter; ii. through-channel endoscopic; or iii. portal; (b) substratification based on intent: i. preoperatively planned or ii. intraoperative (postdural opening) for urgent ventricular drainage. (2) Anatomic comparisons of KM-EP, KP, and variants via (a) cadaveric dissections and (b) magnetic resonance-diffusion tensor imaging computational 3D modeling. RESULTS: A total of 31 studies met inclusion criteria: (a) 9 utilized KP coordinate (1 cm anterior to the coronal suture (y-axis) and 3 cm lateral of the midline (x-axis) approximated by the midpupillary line) and 22 EPs represented variations. All 31 traversed critical subcortical WMTs, specifically the frontal aslant tract, superior longitudinal fasciculus II, and inferior fronto-occipital fasciculus, whereas KM-EP (x = 2.3, y = 3.5) spares these WMTs. CONCLUSION: KP (x = 3, y = 1) conceived over a century ago, prior to awareness of WMTs, as well as its variants, anatomically place critical WMTs at risk. The KM-EP (x = 2.3, y = 3.5) is purpose built and founded on WMTs, representing anatomically safe access to the FH. Correlative clinical safety, which will be directly proportional to the size of the corridor, is yet to be established in prospective studies.

White Matter-Governed Superior Frontal Sulcus Surgical Paradigm: A Radioanatomic Microsurgical Study-Part I.

BACKGROUND: Frontal subcortical and intraventricular pathologies are traditionally accessed via transcortical or interhemispheric-transcallosal corridors. OBJECTIVE: To describe the microsurgical subcortical anatomy of the superior frontal sulcus (SFS) corridor. METHODS: Cadaveric dissections were undertaken and correlated with magnetic resonance imaging/diffusion-tensor imaging-Tractography. Surgical cases demonstrated clinical applicability. RESULTS: SFS was divided into the following divisions: proximal, precentral sulcus to coronal suture; middle, 3-cm anterior to coronal suture; and distal, middle division to the orbital crest. Anatomy was organized as layered circumferential rings projecting radially towards the ventricles: (1) outer ring: at the level of the SFS, the following lengths were measured: (A) precentral sulcus to coronal suture = 2.29 cm, (B) frontal bone projection of superior sagittal sinus (SSS) to SFS = 2.37 cm, (C) superior temporal line to SFS = 3.0 cm, and (D) orbital crest to distal part of SFS = 2.32 cm; and (2) inner ring: (a) medial to SFS, U-fibers, frontal aslant tract (FAT), superior longitudinal fasciculus I (SLF-I), and cingulum bundle, (b) lateral to SFS, U-fibers, (SLF-II), claustrocortical fibers (CCF), and inferior fronto-occipital fasciculus, and (c) intervening fibers, FAT, corona radiata, and CCF. The preferred SFS parafascicular entry point (SFSP-EP) also referred to as the Kassam-Monroy entry point (KM-EP) bisects the distance between the midpupillary line and the SSS and has the following coordinates: x = 2.3 cm (lateral to SSS), y ≥ 3.5 cm (anterior to CS), and z = parallel corona radiata and anterior limb of the internal capsule. CONCLUSION: SFS corridor can be divided into lateral, medial, and intervening white matter tract segments. Based on morphometric assessment, the optimal SFSP-EP is y ≥ 3.5 cm, x = 2.3 cm, and z = parallel to corona radiata and anterior limb of the internal capsule.

An Anatomically-Based Endoscopic Endonasal Model to Navigate the Anterior Ventral Skull Base.

BACKGROUND: Endoscopic endonasal approaches to access the sellar and parasellar regions are challenging in the face of anatomical variations or pathologic conditions. We propose an anatomically-based model including the orbitosellar line (OSL), critical oblique foramen line (COFL), and paramedial anterior line (PAL) facilitating safe, superficial-to-deep dissection triangulating upon the medial opticocarotid recess. METHODS: Five cadaveric heads were dissected to systematically expose the OSL, COFL, and PAL, illustrated with image guidance. Application of the coordinate system and a 6-step dissection sequence is described. RESULTS: The coordinate system consists of 1) the OSL, connecting a) the anterior orbital point, junction of the anterior buttress of the middle turbinate with the agger nasi region, located 34.3 ± 0.9 mm above the intersection of the vertical plane of the lacrimal crest, and the orthogonal plane of the maxillo-ethmoidal suture; b) the posterior orbital point, junction of the optic canal with the lamina papyracea, located 4 ± 0.7 mm below the posterior ethmoidal artery; and c) the medial opticocarotid recess; 2) COFL (15 ± 2.8 mm), connecting the palatovaginal canal, vidian canal, and foramen rotundum; and 3) PAL (39 ± 0.06 mm), connecting the vidian canal with the posterior ethmoidal artery. CONCLUSIONS: OSL, COFL, and PAL form an anatomically-based model for the systematic exposure when accessing the parasellar and sellar regions. Preliminary anatomical data suggest that this model may be of value when normal anatomy is distorted by pathology or anatomic variations.

Awake Surgical Management of Third Ventricular Tumors: A Preliminary Safety, Feasibility, and Clinical Applications Study.

BACKGROUND: Endoscopic and microneurosurgical approaches to third ventricular lesions are commonly performed under general anesthesia. OBJECTIVE: To report our initial experience with awake transsulcal parafascicular corridor surgery (TPCS) of the third ventricle and its safety, feasibility, and limitations. METHODS: A total of 12 cases are reviewed: 6 colloid cysts, 2 central neurocytomas, 1 papillary craniopharyngioma, 1 basal ganglia glioblastoma, 1 thalamic glioblastoma, and 1 ependymal cyst. Lesions were approached using TPCS through the superior frontal sulcus. Pre-, intra-, and postoperative neurocognitive (NC) testing were performed on all patients. RESULTS: No cases required conversion to general anesthesia. Awake anesthesia changed intraoperative management in 4/12 cases with intraoperative cognitive changes that required port re-positioning; 3/4 recovered. Average length of stay (LOS) was 6.1 d ± 6.6. Excluding 3 outliers who had preoperative NC impairment, the average LOS was 2.5 d ± 1.2. Average operative time was 3.00 h ± 0.44. Average awake anesthesia time was 5.05 h ± 0.54. There were no mortalities. CONCLUSION: This report demonstrated the feasibility and safety of awake third ventricular surgery, and was not limited by pathology, size, or vascularity. The most significant factor impacting LOS was preoperative NC deficit. The most significant risk factor predicting a permanent NC deficit was preoperative 2/3 domain impairment combined with radiologic evidence of invasion of limbic structures - defined as a "NC resilience/reserve" in our surgical algorithm. Larger efficacy studies will be required to demonstrate the validity of the algorithm and impact on long-term cognitive outcomes, as well as generalizability of awake TPCS for third ventricular surgery.

Microsurgical Anatomy of the Vertical Rami of the Superior Longitudinal Fasciculus: An Intraparietal Sulcus Dissection Study.

BACKGROUND: A number of vertical prolongations of the superior longitudinal fasciculus, which we refer to as the vertical rami (Vr), arise at the level of the supramarginal gyrus, directed vertically toward the parietal lobe. OBJECTIVE: To provide the first published complete description of the white matter tracts (WMT) of the Vr, their relationship to the intraparietal and parieto-occipital sulci (IPS-POS complex), and their importance in neurosurgical approaches to the parietal lobe. METHODS: Subcortical dissections of the Vr and WMT of the IPS were performed. Findings were correlated with a virtual dissection using high-resolution diffusion tensor imaging (DTI) tractography data derived from the Human Connectome Project. Example planning of a transparietal, transsulcal operative corridor is demonstrated using an integrated neuronavigation and optical platform. RESULTS: The Vr were shown to contain component fibers of the superior longitudinal fasciculus (SLF)-II and SLF-III, with contributions from the middle longitudinal fasciculus merging into the medial bank of the IPS. The anatomic findings correlated well with DTI tractography. The line extending from the lateral extent of the POS to the IPS marks an ideal sulcal entry point that we have termed the IPS-POS Kassam-Monroy (KM) Point, which can be used to permit a safe parafascicular surgical trajectory to the trigone. CONCLUSION: The Vr are a newly conceptualized group of tracts merging along the banks of the IPS, mediating connectivity between the parietal lobe and dorsal stream/SLF. We suggest a refined surgical trajectory to the ventricular atrium utilizing the posterior third of the IPS, at or posterior to the IPS-POS Point, in order to mitigate risk to the Vr and its considerable potential for postsurgical morbidity.

The Surgical White Matter Chassis: A Practical 3-Dimensional Atlas for Planning Subcortical Surgical Trajectories.

BACKGROUND: The imperative role of white matter preservation in improving surgical functional outcomes is now recognized. Understanding the fundamental white matter framework is essential for translating the anatomic and functional literature into practical strategies for surgical planning and neuronavigation. OBJECTIVE: To present a 3-dimensional (3-D) atlas of the structural and functional scaffolding of human white matter-ie, a "Surgical White Matter Chassis (SWMC)"-that can be used as an organizational tool in designing precise and individualized trajectory-based neurosurgical corridors. METHODS: Preoperative diffusion tensor imaging magnetic resonance images were obtained prior to each of our last 100 awake subcortical resections, using a clinically available 3.0 Tesla system. Tractography was generated using a semiautomated deterministic global seeding algorithm. Tract data were conceptualized as a 3-D modular chassis based on the 3 major fiber types, organized along median and paramedian planes, with special attention to limbic and neocortical association tracts and their interconnections. RESULTS: We discuss practical implementation of the SWMC concept, and highlight its use in planning select illustrative cases. Emphasis has been given to developing practical understanding of the arcuate fasciculus, uncinate fasciculus, and vertical rami of the superior longitudinal fasciculus, which are often-neglected fibers in surgical planning. CONCLUSION: A working knowledge of white matter anatomy, as embodied in the SWMC, is of paramount importance to the planning of parafascicular surgical trajectories, and can serve as a basis for developing reliable safe corridors, or modules, toward the goal of "zero-footprint" transsulcal access to the subcortical space.

Transtibial Versus Anteromedial Portal ACL Reconstruction: Is a Hybrid Approach the Best?

BACKGROUND: Improved biomechanical and clinical outcomes are seen when the femoral tunnels of the anterior cruciate ligament (ACL) are placed in the center of the femoral insertion. The transtibial (TT) technique has been shown to be less capable of this than an anteromedial (AM) portal approach but is more familiar to surgeons and less technically challenging. A hybrid transtibial (HTT) technique using medial portal guidance of a transtibial guide wire without knee hyperflexion may offer anatomic tunnel placement while maintaining the relative ease of a TT technique. PURPOSE: To evaluate the anatomic and biomechanical performance of the HTT technique compared with TT and AM approaches. STUDY DESIGN: Controlled laboratory study. METHODS: Thirty-six paired, fresh-frozen human knees were used. Twenty-four knees (12 pairs) underwent all 3 techniques (TT, AM, HTT) for femoral tunnel placement, with direct measurement of femoral insertional overlap and femoral tunnel length. The remaining 12 knees (6 pairs) underwent completed reconstructions to evaluate graft anisometry and tunnel orientation, with each technique performed in 4 specimens and tested using motion sensors with a quad-load induced model. Graft length changes and graft/femoral tunnel angle were measured at varying degrees of flexion. RESULTS: Percentage overlap of the femoral insertion averaged 37.0% ± 28.6% for TT, 93.9% ± 5.6% for HTT, and 79.7% ± 7.7% for AM, with HTT significantly greater than both TT (P = .007) and AM (P = .001) approaches. Graft length change during knee flexion (anisometry) was 30.1% for HTT, 12.8% for AM, and 8.5% for TT. When compared with the TT approach, HTT constructs exhibited comparable graft-femoral tunnel angulation (TT, 150° ± 3° vs HTT, 142° ± 2.3°; P < .001) and length (TT, 42.6 ± 2.8 mm vs HTT, 38.5 ± 2.0 mm; P = .12), while AM portal tunnels were significantly shorter (31.6 ± 1.6 mm; P = .001) and more angulated (121° ± 6.5°; P < .001). CONCLUSION: The HTT technique avoids hyperflexion and maintains femoral tunnel orientation and length, similar to the TT technique, but simultaneously achieves anatomic graft positioning. CLINICAL RELEVANCE: The HTT technique offers an anatomic alternative to an AM portal approach while maintaining the technical advantages of a traditional TT reconstruction.

The Operating Room of the Future Versus the Future of the Operating Room.

Technological advancement in the operating room is evolving into a dynamic system mirroring that of the aeronautics industry. Through data visualization, information is continuously being captured, collected, and stored on a scalable informatics platform for rapid, intuitive, iterative learning. The authors believe this philosophy (paradigm) will feed into an intelligent informatics domain fully accessible to all and geared toward precision, cell-based therapy in which tissue can be targeted and interrogated in situ. In the future, the operating room will be a venue that facilitates this real-time tissue interrogation, which will guide in situ therapeutics to restore the state of health.

Initial experience with a robotically operated video optical telescopic-microscope in cranial neurosurgery: feasibility, safety, and clinical applications.

OBJECTIVE The move toward better, more effective optical visualization in the field of neurosurgery has been a focus of technological innovation. In this study, the authors' objectives are to describe the feasibility and safety of a new robotic optical platform, namely, the robotically operated video optical telescopic-microscope (ROVOT-m), in cranial microsurgical applications. METHODS A prospective database comprising patients who underwent a cranial procedure between April 2015 and September 2016 was queried, and the first 200 patients who met the inclusion criteria were selected as the cohort for a retrospective chart review. Only adults who underwent microsurgical procedures in which the ROVOT-m was used were considered for the study. Preoperative, intraoperative, and postoperative data were retrieved from electronic medical records. The authors address the feasibility and safety of the ROVOT-m by studying various intraoperative variables and by reporting perioperative morbidity and mortality, respectively. To assess the learning curve, cranial procedures were categorized into 6 progressively increasing complexity groups. The main categories of pathology were I) intracerebral hemorrhages (ICHs); II) intraaxial tumors involving noneloquent regions or noncomplex extraaxial tumors; III) intraaxial tumors involving eloquent regions; IV) skull base pathologies; V) intraventricular lesions; and VI) cerebrovascular lesions. In addition, the entire cohort was evenly divided into early and late cohorts. RESULTS The patient cohort comprised 104 female (52%) and 96 male (48%) patients with a mean age of 56.7 years. The most common pathological entities encountered were neoplastic lesions (153, 76.5%), followed by ICH (20, 10%). The distribution of cases by complexity categories was 11.5%, 36.5%, 22%, 20%, 3.5%, and 6.5% for Categories I, II, II, IV, V, and VI, respectively. In all 200 cases, the surgical goal was achieved without the need for intraoperative conversion. Overall, the authors encountered 3 (1.5%) major neurological morbidities and 6 (3%) 30-day mortalities. Four of the 6 deaths were in the ICH group, resulting in a 1% mortality rate for the remainder of the cohort when excluding these patients. None of the intraoperative complications were considered to be attributable to the visualization provided by the ROVOT-m. When comparing the early and late cohorts, the authors noticed an increase in the proportion of higher-complexity surgeries (Categories IV-VI), from 23% in the early cohort, to 37% in the late cohort (p = 0.030). In addition, a significant reduction in operating room setup time was demonstrated (p < 0.01). CONCLUSIONS The feasibility and safety of the ROVOT-m was demonstrated in a wide range of cranial microsurgical applications. The authors report a gradual increase in case complexity over time, representing an incremental acquisition of experience with this technology. A learning curve of both setup and execution phases should be anticipated by new adopters of the robot system. Further prospective studies are required to address the efficacy of ROVOT-m. This system may play a role in neurosurgery as an integrated platform that is applicable to a variety of cranial procedures.

The National Cardiovascular Data Registry Voluntary Public Reporting Program: An Interim Report From the NCDR Public Reporting Advisory Group.

Public reporting of health care data continues to proliferate as consumers and other stakeholders seek information on the quality and outcomes of care. Medicare's Hospital Compare website, the U.S. News & World Report hospital rankings, and several state-level programs are well known. Many rely heavily on administrative data as a surrogate to reflect clinical reality. Clinical data are traditionally more difficult and costly to collect, but more accurately reflect patients' clinical status, thus enhancing the validity of quality metrics. We describe the public reporting effort being launched by the American College of Cardiology and partnering professional organizations using clinical data from the National Cardiovascular Data Registry (NCDR) programs. This hospital-level voluntary effort will initially report process of care measures from the percutaneous coronary intervention (CathPCI) and implantable cardioverter-defibrillator (ICD) registries of the NCDR. Over time, additional process, outcomes, and composite performance metrics will be reported.

The Effect of Arthroscopic Rotator Interval Closure on Glenohumeral Volume.

The role of rotator interval in shoulder pathology and the effect of its closure are not well understood. In addition, the effect of rotator interval closure on intra-articular glenohumeral volume (GHV) remains unknown. We conducted a study to quantify the GHV reduction obtained with an arthroscopic rotator interval closure and to determine whether medial and lateral interval closures resulted in different degrees of volume reduction. We dissected 8 fresh-frozen cadaveric shoulders (mean age, 64.4 years) to the level of the rotator cuff. Volumetric measurements were taken before and after medial and lateral rotator interval closure incorporating the superior glenohumeral ligament and the upper portion of the subscapularis. Arthroscopic closure of the rotator interval with 2 sutures reduced GHV by a mean of 45%. More volume reduction resulted with use of a single lateral interval closure stitch than with use of a single medial stitch (35% vs 24%; P < .02). Arthroscopic rotator interval closure with 2 plication stitches is a powerful tool in reducing intracapsular volume of the shoulder and may be a useful adjunct in restoring glenohumeral stability. If a single plication stitch is preferred, a lateral stitch (vs a medial stitch) can be used for a significantly larger reduction in shoulder volume.

Getting to goal in newly diagnosed type 2 diabetes using combination drug "subtraction therapy".

BACKGROUND: The treatment of newly diagnosed type 2 diabetes mellitus is diverse, with no clear consensus regarding the initial drug regimen or dosing to achieve optimal glycemic control. METHODS: We treated 44 consecutive patients with newly diagnosed type 2 diabetes with maximally tolerated doses of pioglitazone 45 mg/day, metformin 1000-2000 mg/day, and repaglinide 1-4 mg before meals. The doses and drugs were subsequently decreased ("subtraction therapy") to achieve optimal glycemic control and minimize side effects. Three primary outcomes were measured: the short term HbA1c response, the long term HbA1c response, and the incidence of hypoglycemia. RESULTS: All 44 patients responded with a rapid, progressive decline in their HbA1c levels from 11.43±2.3% to 6.17±0.72% (101±25.1 mmol/mol to 44±7.9 mmol/mol) by three months, and remained stable thereafter. An HbA1c ≤7.0% (≤53 mmol/mol) was reached within 1-4 months in 42 of 44 patients, and in every patient by 12 months. Each patient's lowest HbA1c level, 5.65±0.6% (38±6.6 mmol/mol), was reached over 6.3±2.9 months. Patients with initial HbA1c levels >10% (>86 mmol/mol) (n=33) responded similarly as those with HbA1c levels <10% (<86 mmol/mol) (n=11). Combination drug therapy maintained HbA1c levels between 5.0 and 7.0% (31 and 53 mmol/mol) for up to 14.83 years. Only one clinically significant hypoglycemic event occurred during 261.08 person-years of follow-up. CONCLUSIONS: In our experience, combination drug "subtraction therapy" was safe and effective for treating all newly diagnosed type 2 diabetic patients.